Atlas of Gynecologic Surgical

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 Atlas of
Gynecologic
Surgical
Pathology
 Atlas of
Gynecologic
Surgical
Pathology Fourth Edition

Philip B. Clement, MD
Emeritus Professor of Pathology, University of British Columbia and
Department of Pathology, Vancouver General Hospital and Health Sciences Center
Vancouver, BC, Canada

Jennifer N. Stall, MD
Director of Gynecologic and Obstetric Pathology
Hospital Pathology Associates
Minneapolis/St. Paul, MN, USA

Robert H. Young, MD, FRCPath

Pathologist, Massachusetts General Hospital
Robert E. Scully Professor of Pathology
Harvard Medical School
Boston, MA, USA

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Third edition 2014

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vi
Dedication
To the Memory of Robert E. Scully, MD
The last edition of this book was published not long after we
lost one of the giants of pathology, Dr. Robert E. Scully, to
whom this book has been dedicated since its inception. In this
dedication we briefly highlight his career and personality for
those not privileged to have known him. Various other apprecia-
tions provide further details [1–3].
Dr. Scully passed away two months after his 91st birthday.
Two of us (PBC, RHY) had the pleasure and privilege of a close
association with him for over 40 years and 30 years, respectively.
That experience is the defining aspect of our careers and one we
will always cherish. As well as providing a unique example of
practicing pathology at the highest level, his personal qualities
of gentleness, kindness, and humility were an example to all
who had the good fortune to know him. JNS owes her own debt
to him through his material that she had the opportunity to
study (for one year funded by a bequest of Dr. Scully), as noted
in the Preface. In addition to all he taught us, in person and
through his legacy, Dr. Scully during his life allowed us free access
to his great collection of over 27,000 consultation cases and,
fortunately, it is still available in the office of one of us (RHY).
Dr. Scully practiced general surgical pathology until the last
two decades of his career after which he focused on gynecologic
and testicular pathology, although still serving as a consultant
for a wide variety of cases. His diagnostic prowess is the stuff of
legend for generations of trainees and faculty who experienced
his quick yet thorough eye. He excelled in all areas: diagnosis,
teaching, and research, the latter largely studies emphasizing
clinicopathologic correlation and recognition of the distinctive
morphologic features of many new entities. It is humbling for
us all to realize that his last publication was in 2006, 58 years
after his first. His curriculum vitae included 503 contributions,
320 of them original peer-reviewed contributions.
Dr. Scully described many now well-known entities, among
which are gonadoblastoma (the gonadal tumor of intersex) and
ovarian tumors such as juvenile granulosa cell tumor, small cell
carcinoma of hypercalcemic type, retiform Sertoli–Leydig cell
tumor, and sclerosing stromal tumor. Some of those entities are
in the sex cord–stromal family indicative of his lifelong great interest
in that area that began in the mid-1950s when he co-authored
a book Endocrine Pathology of the Ovary, published in 1958. That
volume quickly established his reputation as an expert on ovarian
tumors and the number of consultation cases he received grew
dramatically after that to reach, in the peak decades of his career,
an average of about 10 per day. These cases encompassed the entire
spectrum of gynecologic pathology as well as many testicular
lesions and even general surgical pathology cases of diverse
nature. His collection was the source for many original articles
over the years as well as numerous reviews, those on ovarian sex
cord–-stromal tumors and metastatic tumors to the ovary being
among the most noteworthy. Within the area of uterine pathology
he wrote major studies on müllerian adenosarcoma. uterine tumors
resembling ovarian sex cord tumors, myxoid leiomyosarcoma,
endometrial carcinomas (micropapillary endometrioid carcinoma
and the MELF pattern of myoinvasive endometrioid carcinoma),
as well as cervical entities such as adenoid basal carcinoma,
mesonephric remnant hyperplasia (and carcinomas derived from
them) and other benign mimics of neoplasia. Although he felt
that the clinical, gross, and microscopic features usually led to the
correct diagnosis. he was always curious and wrote one of the first
review articles on the immunohistochemistry of ovarian tumors.
Dr. Scully played an important role in the diethylstilbestrol (DES)
story. In the mid- to late 1960s he noticed an unusual surge of
MGH cases of clear cell adenocarcinoma of the vagina and cervix
in young women. This prompted his clinical colleagues to be on
the alert for a possible explanation, which eventually came to pass.
A few years after the first edition of this book was published
in 2000, Dr. Scully retired from his position as senior pathologist
at the Massachusetts General Hospital and Professor of Pathol-
ogy at Harvard Medical School, after a truly remarkable career
spanning almost 55 years. His career, based on astounding
hard work (he was usually in the office seven days a week),
awareness of the priority of patient care, a balanced approach
(taking appropriate note of clinical and gross features), and
a superb eye, is one that we can all strive to emulate. We will
always be confident that no one looked at more gynecologic
specimens more carefully, and with greater benefit to mankind,
than Dr. Scully.
Philip B. Clement, MD
Jennifer N. Stall, MD
Robert H. Young, MD
References
1. Clement PB, Young RH. An appreciation of Robert E. Scully, MD,
and an introduction to a symposium in his honor on recent
advances in gynecologic pathology. Hum Pathol 1991;22:
737–746.
2. Young RH, Clement, PB. History of gynecological pathology. XXX:
Robert E. Scully, MD. Int J Gynecol Pathol 2016;36:2–23.
3. Rosai J. A tribute to Robert E. Scully on his 80th birthday. Semin
Diagn Pathol 2001;18:151–154.

Preface to the Fourth Edition
The aims of the fourth edition of the Atlas of Gynecologic
Surgical Pathology remain the same as those of the previous
three editions, the first published in 2000. It is intended to be
an easy-to-use practical guide to the diagnosis of lesions of
the female reproductive system and peritoneum. The manner
of presentation will help the reader assimilate the essential
information about the numerous lesions discussed and illus-
trated. The text is extensive and has been thoroughly revised
and updated with the addition of approximately 1000 new
references. In accord with our desire for the volume to retain
its compact size and user-friendly format, the references, which
occupied about one-sixth of the previous edition, are now
available exclusively online. This decision, which was not taken
lightly, allows more space for new text, many additional figures
and the listing of many more recent citations than would
otherwise have been possible as well as classic older references,
some of which still remain the best study of a particular lesion.
Accessing the references online also allows a link with the
respective abstracts in PubMed.
The emphasis in this book is on the diagnosis of neoplas-
tic and pseudoneoplastic lesions. Although the focus is on
common lesions, less common and even rare lesions are also
discussed. Diagnosis of the lesions covered can in most cases
be accomplished by careful evaluation of routinely stained
slides, and, accordingly, the vast majority of the illustrations
are of such preparations. Gross examination plays an important
role in evaluating certain specimens from the female genital
tract, and we have included some such illustrations, although
space constraints preclude illustrating every entity. The clinical
background may also be important when evaluating gyneco-
logic tumors: basic features such as the age of the patient and
clinical history may be crucial in formulating a differential
diagnosis, especially when dealing with an ovarian tumor,
and accordingly are emphasized when indicated, and the first
chapter considering ovarian neoplasms includes tables high-
lighting important aspects in this regard. A detailed knowledge
of the normal histology of the female reproductive system is
important as a background for evaluating the pathology of this
area. Some of these aspects are discussed briefly but are not
considered in detail because a standard text in this area is readily
available [1].
Each chapter begins with a heading outline so that its
contents can be appreciated at a glance. The 20 chapters are
organized by site and the text is arranged in concise, point form
that highlights the cardinal clinical, gross, and microscopic
features and the differential diagnoses. Immunohistochemical
findings are also included, with an emphasis on those that are
the most diagnostically useful. A similar comment pertains to
molecular studies. The histological classifications of the tumors
are those of the World Health Organization classifications of
tumors of the female genital tract, with occasional minor
modifications. Our approach is essentially that we learned
from Dr. Scully during our years working with him on his
fascicle [2] and many original manuscripts, or as handed down
in the form of his remarkable collection of insightful second
opinions, countless of which we have had the privilege to read.
We hope that the pathologist, both in academic practice and
vii
community practice, will find this work helpful in evaluating
the numerous, often challenging specimens and perplexing
microscopic patterns [3] that may be seen in female genital tract
specimens. Additionally, clinicians with a particular interest
in this area will also find this work a useful source of helpful
information and reference material.
The two authors who have been involved since its inception
would like to warmly welcome our new co-author, Dr. Jennifer
N. Stall. She recently spent two years at the Massachusetts
General Hospital (MGH), the first as the Robert E. Scully Fellow
in Gynecologic Pathology, and the second a unique year as
the Surgical Pathology Fellow for the Robert E. Scully Col-
lection. During these two years she worked closely with one
of us (RHY) and was of great assistance by offering learned
opinions on many of the challenging referral cases sent to
him, in continuation of the tradition forged by Dr. Scully
that has resulted in the existence of a magnificent collection
of cases spanning the entire field of gynecologic pathology.
Whereas we are nearing the end of our careers, Dr. Stall is at
the beginning of what we know will be a great career given her
remarkable talents as a physician and pathologist. We cannot
imagine better ‘new blood’ to continue what we are proud
to say has been a successful endeavor. We thank her for her
contributions to this edition, which has included numerous
suggestions for improving the overall quality of the work. The
Preface concludes with Dr. Stall’s own remarks.
‘I would like to thank Drs. Clement and Young for inviting
me to be a co-author of the fourth edition of this textbook.
Although I never had the privilege of working with the book’s
dedicatee, Dr. Scully, I have been aware since early in my train-
ing of his remarkable contributions to the field of gynecologic
pathology. As a result of my time spent working with Dr. Young
and his other colleagues at the MGH, my awareness of Dr.
Scully’s impact on the field and admirable personal qualities
has only been heightened. Furthermore, I had the remarkable
opportunity in my second at the MGH, to review thousands
of the cases in Dr. Scully’s collection and it was a treat. It was
an honor, not only to see the cases but to read his remarkable
detailed opinion letters which were an education in and of
themselves. Much of the material accrued for this book has
been from Dr. Scully’s collection. My co-authors and I know he
would be happy that it has been used for educational purposes
to further understanding of gynecologic pathology and improve
patient care across the globe.’
Philip B. Clement, MD
Jennifer N. Stall, MD
Robert H. Young, MD, FRCPath
References
1. Mills SE, ed. Histology for pathologists. 4th ed. New York: Lippincott
Williams & Wilkins; 2012.
2. Scully RE, Young RH, Clement PB. Tumors of the ovary,
maldeveloped gonads, fallopian tube, and broad ligament. Armed
Forces Institute of Pathology, Third Series; 1998.
3. Young RH, Scully RE. Differential diagnosis of ovarian tumors
based primarily on their patterns and cell types. Semin Diagn
Pathol 2001;18:161–235.

Non-Neoplastic Lesions and Benign
and Locally Aggressive Tumors of
the Vulva
VIRAL INFECTIONS
Human Papillomavirus
(Including Condyloma
Acuminatum)
Herpes Virus
Other Viral Infections
NONVIRAL INFECTIONS
Syphilis
Granuloma Inguinale
Lymphogranuloma Venereum
Chancroid
Tuberculosis and
Nontuberculous Mycobacterial
Infection
Necrotizing Fasciitis and
Progressive Bacterial
Synergistic Gangrene
Other Bacterial Infections
Fungal Infections and Parasitic
Infestations
NON-NEOPLASTIC EPITHELIAL
DISORDERS
Lichen Sclerosus
Squamous Cell Hyperplasia,
NOS
Other Dermatoses
SQUAMOUS
PAPILLOMATOSIS
PIGMENTED LESIONS
Lentigo Simplex and
Melanosis
Usual Melanocytic Nevi
Atypical Genital Nevi
FIBROEPITHELIAL POLYP
CYSTS
Bartholin’s Duct Cyst
Mucinous and Ciliated
Vestibular Cysts
Other Cysts
NONINFECTIOUS
INFLAMMATORY LESIONS
Vulvar Vestibulitis
Plasma Cell Vulvitis (Zoon’s
Vulvitis)
Granulomatous Vulvitis and
Vulvar Involvement by Crohn’s
Disease
CHAPTER 1
Behçet’s Disease
Florid Reactive Lymphoid
Hyperplasia (Lymphoma-like
Lesion)
Graft-versus-Host Disease
Sjögren and Non-Sjögren Sicca
Syndromes
Ligneous Vulvitis (see
Chapter 4)
REACTIVE LESIONS
Reactive Atypia and
Multinucleated Keratinocytes
Nodular Fasciitis
Postoperative Spindle Cell
Nodule
Lesions Related to
Lymphedema, Immobilization,
and Repetitive Trauma
OTHER NON-NEOPLASTIC
LESIONS
Endometriosis
Multinucleated Stromal Giant
Cells
Adenosis
Ectopic Breast Tissue and
Rarer Ectopias
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 1.e1

Keywords
viral and nonviral vulvar infections
non-neoplastic epithelial vulvar disorders
squamous papillomatosis
pigmented vulvar lesions
vulvar fibroepithelial polyp cysts
noninfectious inflammatory vulvar lesions
reactive vulvar lesions
non-neoplastic vulvar lesions
benign epithelial vulvar tumors
benign mesenchymal tumors of the lower genital tract
locally aggressive mesenchymal tumors of the lower
genital tract
2 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva

Nodular Hyperplasia of Benign Mammary-type Tumors Superficial Angiomyxoma

Bartholin’s Gland Benign Tumors of Bartholin’s (Cutaneous Myxoma)
Varices Gland and Minor Vestibular Cellular Angiofibroma
Amyloidosis Glands Superficial Myofibroblastoma
Miscellaneous Other Lesions Myoepithelioma-like Tumors Prepubertal Vulvar Fibroma
Tubulovillous Adenoma Lipoblastoma-like Tumor
Leiomyoma and
BENIGN EPITHELIAL TUMORS Rhabdomyoma
BENIGN AND LOCALLY Fibrous, Adipocytic, Vascular,
Papillary Hidradenoma AGGRESSIVE MESENCHYMAL and Neural Tumors
(Hidradenoma Papilliferum)
TUMORS OF THE LOWER Solitary Fibrous Tumor
and Other Apocrine Tumors
GENITAL TRACT Granular Cell Tumor
Other Benign Tumors of Skin
Appendage Origin Aggressive Angiomyxoma
Seborrheic Keratosis Angiomyofibroblastoma

VIRAL INFECTIONS

prominent but may be focal or even absent. ‘Condyloma

HUMAN PAPILLOMAVIRUS (HPV)
(INCLUDING CONDYLOMA ACUMINATUM)
Clinical and gross features (Fig. 1.1)
■ Sexually transmitted HPV (usually low-risk types,
especially HPV 6 and 11) is the cause of condyloma
acuminatum (venereal wart), the incidence of which in
the USA increased 4- to 5-fold between 1966 and 1981.
■ Condylomas, which are considered LSIL/VIN1, most
commonly involve the vestibule and the medial aspects
of the labia majora and vary from only colposcopically
visible lesions to small excrescences to large, sessile or
pedunculated, white to red, cauliflower-like masses that
may be multiple or confluent.
■ Synchronous or metachronous condylomas,
precancerous changes, or invasive squamous cell
carcinoma (ISqCC) may occur locally, including the
perineal and perianal skin and the mucosa of the anus,
urethra, vagina, and cervix.
■ The clinical course is typically protracted unless the
lesions are ablated or removed. They may enlarge and
increase in number during pregnancy but can regress
postpartum.
■ Srodon et al. found that condylomas harbored a low-risk
HPV in 67% of cases, but 42% contained a high-risk
HPV that may account for the progression of some
condylomas to high-grade VIN or ISqCC.
Histologic features (Figs. 1.2–1.5)
■ Fully developed condylomas are characterized by simple
to complex branching papillae of acanthotic squamous
epithelium and fibrovascular cores. Flat condylomas
occur but are less common in the vulva than in the
cervix (see Chapter 5).
■ The pathognomonic koilocytes (HPV-infected
keratinocytes) in the superficial layers are usually
without cytopathic effect’ has been applied in the latter
situation, but ‘squamous papilloma, possibly condyloma’
may be preferable given the implications of a condyloma
diagnosis.
■ The variably sized koilocytes have a perinuclear halo of
clear cytoplasm typically surrounded by a peripheral
zone of condensed amphophilic cytoplasm. Their
hyperchromatic, granular or smudgy, enlarged to
shrunken nuclei have an irregular contour (‘koilocytotic
atypia’); binucleated or multinucleated cells are
common. Occasional mitoses, usually confined to the
lower third of the epithelium, may be seen.
■ Ki67 expression is present in the upper two-thirds
of the epithelium and correlates with the presence
of HPV.
■ p16 staining is typically focal, cytoplasmic, and often in
the upper layers (consistent with LSIL), although rare
condylomas harbor foci of HSIL (as noted above) with
typical diffuse (block) p16 staining (Sulaiman et al.)
necessitating thorough sampling. Lewis et al. found focal
block p16 staining in 4% of lesions they considered flat
vulvar LSILs, although most investigators equate block
staining with HSIL.
■ Nonspecific features include para/orthokeratosis,
hypergranulosis, parabasilar hyperplasia, and underlying
superficial chronic inflammation.
■ Variant condyloma phenotypes:
• Seborrheic keratosis (SK)-like condyloma. HPV+
SK-like lesions have also been referred to as
‘condyloma with features of SK’ (see Seborrheic
Keratosis).
• Condyloma with pseudobowenoid change. Apoptosis
in the superficial keratinocytes with chromatin
dispersal or clumping and cytoplasmic condensation
and retraction results in a dense hyaline globule (the
residue of a dead cell). The appearance may suggest
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 3

Fig. 1.1 Condylomata acuminata. The vulva is involved by confluent Fig. 1.2 Condyloma acuminatum. Low-power view shows typical
condylomas. papillary configuration.

Fig. 1.3 Condyloma acuminatum. Multiple papillary projections with Fig. 1.4 Condyloma acuminatum. Epithelial hyperplasia with focal
hyperkeratosis range from rounded to spired. koilocytes, hypergranulosis, and surface papillary projections are seen.

VIN, but nuclear atypia and mitotic activity in the

lower layers are absent.
• Epidermodysplasia verruciformis-like condylomas.
Pohthipornthawat et al. described this flat condyloma
variant in immunosuppressed women (with
β papilloma virus type 5 infection) that exhibited
acanthosis, variable hyperkeratosis, and enlarged cells
with blue-gray cytoplasm, and occasional perinuclear
halos. Atypical nuclei are found only superficially or
extending through the full epidermal thickness.
■ Podophyllin treatment results in mitotic arrest in the
lower epidermis, karyorrhexis, and cellular swelling. In
contrast to VIN, nuclear atypia is mild and confined to
the upper layers. A history of recent treatment is
obviously helpful.
Differential diagnosis (Figs. 1.6–1.7)
■ Verruca vulgaris (HPV type 2) infection:
• Aguilera-Barrantes et al. found that 41% of vulvar
Fig. 1.5 Pseudobowenoid change in a condyloma (see text). warts in girls <5 years of age contained HPV 2 (likely
4 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva

Fig. 1.6 Verruca vulgaris.

nonvenereal), the remainder HPV 6/11 (vs 3% HPV 2

and 94% HPV 6/11 in adults). Fig. 1.7 Epidermolytic hyperkeratosis. The papillary epithelial
• HPV 2-related vulvar lesions resembled typical hyperplasia and cytoplasmic clearing may lead to the consideration of
verruca vulgaris including marked hyperkeratosis. a condyloma. However, viral cytopathic effect is not seen, and the
• HPV testing of vulvar warts in children can be prominent reticular degeneration and hypergranulosis of the stratum
diagnostically helpful. granulosum and spinosum with the hyperkeratosis is characteristic of
epidermolytic hyperkeratosis.
■ Squamous papilloma (vs condyloma with loss of
koilocytosis). Ki-67+ cells in the upper epithelial layers
indicate condyloma.
■ Vestibular papillomatosis (see corresponding heading).
These squamous papillomas are typically confined to the
vestibular area, are usually smaller than condylomas,
and typically lack koilocytosis and hyperkeratosis.
■ Condyloma lata (see Syphilis).
■ Epidermolytic hyperkeratosis. This lesion exhibits
acanthosis, compact papillomatous hyperkeratosis, and
dissolution of the suprabasilar epithelium resulting in
perinuclear clear zones. Keratohyaline clumping and
dyskeratosis resulting in intracellular eosinophilic
globules facilitate distinction from condyloma.
■ Warty VIN and warty ISqCC. Unlike typical condylomas,
these lesions (Chapter 2) have nuclear atypia and
mitoses in all epithelial layers, typically strong and
diffuse ‘block’ p16 staining, and in some, invasion.
■ Verrucous carcinoma (Chapter 2). These usually large
solitary highly differentiated SqCCs occur in older
women and are usually HPV-negative. They lack the fine
branching papillae and koilocytosis of condylomas and
have a well-circumscribed deep border formed by broad
bulbous pegs. Fig. 1.8 Herpetic infection. There is marked ulceration with an
■ Papillary SqCC, NOS. These lesions are rare in the vulva inflammatory exudate and two centrally located multinucleated cells
and are composed of obviously malignant cells that lack with ground glass nuclei (top). Immunohistochemical staining for HSV
koilocytosis. is positive in the multinucleated cells (bottom).

■ The clinical presentation can include vulvar pain,

HERPES VIRUS (Fig. 1.8)
■ Most cases of herpetic vulvitis are due to sexually
transmitted herpes simplex (HSV) type 2, or less
commonly, HSV-1.
inguinal lymphadenopathy, malaise, and fever, with
sequential appearance of vesicles, pustules, and
painful ulcers, often with synchronous involvement
of the perineum, perianal skin, cervix, vagina, and
urinary tract.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 5
Fig. 1.9 CMV infection. Excision for carcinoma in situ (top, left) shows
marked ulceration with prominent inflammation (top, right)). Enlarged
endothelial cells with intranuclear inclusion which were positive with
a CMV immunostain are seen on high power (bottom). (Courtesy of Dr.
Judith A Ferry)
■ The lesions persist for 2–6 weeks and heal without
scarring. Rarely, chronic hypertrophic herpetic vulvitis
clinically simulates a neoplasm or harbors carcinoma.
■ Detection of HSV-2-specific antibodies is diagnostic.
Antibodies in many women without a history of
infection indicate that subclinical infections are
common.
■ A smear or biopsy of a new lesion reveals the
characteristic ground-glass nuclei or eosinophilic
intranuclear inclusions. Cells infected by HSV-1 or
herpes zoster have a similar appearance.
■ Recurrent episodes are common but are usually much
milder, often inconspicuous, and become less frequent.
■ Vulvitis secondary to herpes zoster (varicella) infection is
rare, usually occurring in postmenopausal women who
present with vulvar pain usually followed by unilateral
vesicles and ulcers. Recurrent similar episodes are
common.
NONVIRAL INFECTIONS
SYPHILIS
■ Vulvar syphilis is rare. The primary lesion or
chancre forms within days or several months of
initial contact. The secondary phase is evident by
6 months as a mucocutaneous rash and papules
(condyloma lata). Tertiary lesions (gummas) are
uncommon.
Fig. 1.10 Molluscum contagiosum. Typical low-power view showing
well-delineated aggregates of eosinophilic material (top). The
characteristic intracytoplasmic viral inclusions which displace the
nucleus are seen on high power (bottom).
OTHER VIRAL INFECTIONS (Figs. 1.9–1.10)
■ Cytomegalovirus (CMV) causes an ulcerative
vulvovaginitis resembling herpetic infection; HIV+
women are most susceptible. Characteristic
CMV-inclusion bodies in epithelial and endothelial cells
are detectable with routine and immunohistochemical
stains, culture, or by PCR.
■ Molluscum contagiosum can be venereally transmitted
resulting in vulvar and perineal lesions that are often
asymptomatic and overlooked by patients and
physicians. The histologic features are similar to those
involving extravulvar sites.
■ Human immunodeficiency virus (HIV) is cultured from
some genital ulcers in HIV+ women, and may cause or
exacerbate genital ulcers in this population.
■ Epstein–Barr virus is a rare cause of painful vulvar
ulcers and may be associated with mononucleosis.
■ Chancres are superficial ulcers whereas condylomata
lata are nonulcerated lesions with marked acanthosis
and papillomatosis, often accompanied by intraepidermal
neutrophils. In both lesions, a perivascular
plasmacellular infiltrate with endothelial proliferation
suggests the diagnosis.
■ Organisms can be confirmed by a Warthin–Starry stain.
Dark-field examination or immunofluorescent staining
6 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
of lesion-derived serum and serologic studies can also
facilitate the diagnosis.
GRANULOMA INGUINALE
■ This disorder is caused by the gram-negative bacterium
Calymmatobacterium granulomatis. The primary lesions
(vulvar, vaginal, cervical) are painless papules or ulcers
that appear within a month of exposure (sexual contact
or fecal contamination).
■ The ulcers can persist for years and mimic a neoplasm,
including ISqCC. Lymphatic spread can result in brawny
vulvar edema or parametrial or retroperitoneal
involvement.
■ Unlike lymphogranuloma venereum, inguinal
lymphadenopathy is uncommon but can be mimicked by
inguinal abscesses that often ulcerate.
■ Granulation tissue with neutrophils, plasma cells, and
vacuolated histiocytes contain coccoid to bacillary
organisms (Donovan bodies) demonstrable within the
vacuoles by Giemsa or Warthin–Starry staining of tissue
sections or touch imprints, or by culture.
LYMPHOGRANULOMA VENEREUM
■ This venereal disease is caused by Chlamydia trachomatis.
An initial ulcer is followed by painful inguinal
lymphadenitis (buboes) that can rupture and drain
through the skin. Later, chronic lymphatic obstruction
can result in nonpitting vulvar edema and vaginal and
rectal fibrosis (sometimes with strictures).
■ The inflammatory infiltrate is nonspecific (lymphocytes,
plasma cells, histiocytes including giant cells). Diagnosis
rests on the characteristic clinical findings, culture,
immunostaining, and complement fixation tests.
CHANCROID
■ This venereal disease, which is caused by the
gram-negative bacillus Haemophilus ducreyi, presents
with painful, often purulent, vulvar ulcers and tender
inguinal lymphadenopathy.
■ The ulcer consists of a superficial zone, a middle zone
with characteristic vascular changes, and a deep zone
with a lymphocytic and plasma cell infiltrate.
■ Gram stains of tissue sections or smears may reveal the
organisms in the superficial zone but definite diagnosis
requires culture identification.
TUBERCULOSIS AND NONTUBERCULOUS
MYCOBACTERIAL INFECTION
■ Vulvar tuberculosis is rare and usually due to direct or
lymphatic spread from other sites in the FGT that are
usually due to blood-borne spread from pulmonary
tuberculosis.
■ The lesion begins as a nodule that later ulcerates and
may drain caseous material and pus through one or
more sinuses. Epidermal hyperplasia may result in a
warty tumor-like mass (hypertrophic tuberculosis).
■ There is typical granulomatous inflammation with
caseation. Diagnosis requires acid fast stains and/or
culture or molecular testing to identify the organisms
(Mycobacterium tuberculosis or occasionally atypical
mycobacteria).
■ Nontuberculous mycobacterial infection can clinically
mimic invasive cancer as exemplified by a cervical case
in an immunocompetent woman (Ukita et al.).
■ The differential includes noninfectious forms of
granulomatous vulvitis (see corresponding
heading).
NECROTIZING FASCIITIS AND
PROGRESSIVE BACTERIAL SYNERGISTIC
GANGRENE
■ Vulvar involvement by these disorders, which represent
mixed synergistic bacterial infections, is often associated
with diabetes mellitus and/or atherosclerosis.
■ Necrotizing fasciitis presents with vulvar erythema,
edema, and pain, followed by rapidly progressive dark
discoloration, bullae, and necrosis of the skin,
subcutaneous tissue, and fascia; toxic shock syndrome
is a rare complication. Fatalities can occur without
prompt excision of involved tissues and antibiotic
therapy.
■ Progressive synergistic gangrene, unlike necrotizing
fasciitis, is a slow process that can involve fascia with
less severe systemic manifestations. It is more likely to
develop in postoperative wounds, whereas necrotizing
fasciitis is prone to develop at sites of minor injury.
OTHER BACTERIAL INFECTIONS
■ Infection of Bartholin’s gland (bartholinitis) is usually
caused by sexual transmission of Neisseria gonorrhoeae or
Chlamydia trachomatis; occasional cases follow
vulvovaginal operations. Complications include
Bartholin’s abscess (sometimes with secondary
infection by anaerobic bacteria) and, rarely, toxic
shock syndrome.
■ Hidradenitis suppurativa is a chronic suppurative
process of the vulvar and inguinal apocrine sweat glands
that often results in scarring and draining sinuses.
Microscopic examination reveals acute and chronic
inflammation and apocrine glands dilated with
keratinaceous material. Chronic cases have been
complicated by SqCC.
■ Rare cases of vulvar bacillary angiomatosis occur and
can result in a mass. Microscopic examination reveals a
lobular epithelioid vascular proliferation and bacteria
(Bartonella henselae or Bartonella quintana) that stain with
the Warthin–Starry method.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 7

■ Erythrasma, a chronic infection of the vulvar and

perianal skin, is due to the bacterium Corynebacterium
minutissimum, and usually diagnosed by Wood’s lamp
examination.
■ Rare cases of vulvar malakoplakia, involvement by
Actinomyces israelii, or botryomycosis have been
reported.

FUNGAL INFECTIONS AND PARASITIC

INFESTATIONS (Fig. 1.11)
■ Chronic fungal infections of the vulvar and perianal
skin are commonly caused by Candida albicans and
dermatophytes. Vulvovaginal candidiasis results in
pruritic, moist, red lesions that exhibit spongiosis
and intraepithelial and dermal neutrophils. PAS or
GMS stains and cultures can confirm the diagnosis,
but a paucity of organisms can cause false-negative
results.
■ In developed countries, rare vulvar parasitic infestations
include enterobiasis, schistosomiasis, and myiasis, the
last due to infestation of the larva of the muscoid fly and
sarcophaga. Enterobiasis and late cutaneous vulvar
schistosomiasis can elicit striking pseudoepitheliomatous
hyperplasia that can mimic SqCC if the organisms are
not appreciated. These diseases are common in certain
parts of the world.

Fig. 1.11 Fungal (candidal) vulvitis, H&E (top) and PAS (bottom)
stains.

NON-NEOPLASTIC EPITHELIAL DISORDERS

Classification* autoimmune gastritis, Hashimoto’s thyroiditis, and

1. Lichen sclerosus
2. Squamous cell hyperplasia
3. Other dermatoses
LICHEN SCLEROSUS
Clinical and gross features (Fig. 1.12)
■ Lichen sclerosus (LS) accounts for 30–40% of
non-neoplastic epithelial vulvar lesions. It may occur at
any age, including in children, but is most common in
postmenopausal patients.
■ The etiology is unknown, but recent evidence indicates
that it is a chronic T-cell-mediated inflammatory
dermatosis.
• LS is associated with autoantibodies and in some
cases systemic autoimmune diseases, such as
*Formulated by the International Society for the Study of Vulvar Disease (ISSVD) and the
International Society of Gynecological Pathologists (ISGyP).
extragenital psoriasis.
• Up to 50% of cases have a monoclonally rearranged
T-cell receptor γ-chain gene, the T-cells having an
immunoprofile of an antigen-mediated immune
response.
• A familial occurrence and HLA class II DQ antigen
restrictions in some cases suggest genetic factors.
• Hormonal factors may play a role. Some patients have
low serum levels of dihydrotestosterone, free
testosterone, and androstenedione, and respond to
topical testosterone. Lagerstedt et al. found that
~80% of childhood-onset and ~50% of adult-onset
LS had decreased ERα staining.
■ LS may be asymptomatic but often causes pruritus,
burning, and dyspareunia. Any part of the vulva can be
involved by irregular, ill-defined, white patches. Focal red
and brown areas can be due to dilated vessels and
melanin incontinence, respectively. Synchronous vulvar
lichen planus is present in some cases (see Differential
Diagnosis).
8 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
Fig. 1.12 Lichen sclerosus.
Fig. 1.14 Lichen sclerosus. In contrast to Fig. 1.13, this example
shows prominent edema within the collagenized dermis.
■ Hart et al. found that the labia minora were involved in
68% of cases, the labia majora in 60%, the clitoris in
51%, the perineum in 41%, and the posterior fourchette
in 36%. Almost 90% of the lesions are multiple.
Bilateral, sometimes symmetrical, lesions are common.
■ Vaginal involvement occurs in rare cases. Extragenital
lesions occur in two-thirds of children with vulvar LS,
but in only about 10% of adults.
■ Longstanding LS in adults can result in shiny and
wrinkled skin, atrophic labia, a narrowed introitus, and
agglutination and scarring of the prepuce and frenulum
that may obscure the clitoris. Complications, especially
in children, include anal fissures and perianal and
genital ulcers.
Microscopic features (Figs. 1.13–1.15)
■ Well-developed lesions exhibit a subepithelial edematous
to hyalinized zone with a loss of elastic fibers, usually
subtended by a band of lymphocytes.
■ Additional findings may include spongiosis, vacuolar
alteration and squamatization of basal keratinocytes,
intraepithelial lymphocytes, prominent thickening of the
basement membrane, and sclerosis and/or ectasia of
dermal vessels.
Fig. 1.13 Lichen sclerosus. The typical homogenized collagen beneath
the epithelium is conspicuous and underlying it is prominent chronic
inflammation in a somewhat band-like manner.
Fig. 1.15 Lichen sclerosus with adjacent differentiated vulvar
intraepithelial neoplasia. Lichen sclerosus (left) and typical ‘glassy’
cytoplasm with basal atypia of differentiated VIN (right).
■ A perivascular lymphocytic infiltrate and a lymphocytic
vasculitis occurs, respectively, in up to two-thirds and
half of vulvar LS, but can be focal and subtle (Regauer
et al., 2004).
■ ‘Hypertrophic’ LS, characterized by prominent
dyskeratosis and parakeratosis, was found in 20% of
cases encountered by Weyers, mostly in elderly women.
Unlike differentiated VIN (dVIN), there was no
significant atypia, nuclear crowding, mitotic activity, or
subsequent SqCC.
■ Associated lichen simplex chronicus and/or squamous
hyperplasia are more common than in extravulvar LS
and can result in detached dermal squamous cell nests
that may suggest invasion. Unlike the latter, the nests
lack atypia, are confined to the abnormal collagen, and
are not associated with dVIN (Chapter 2).
■ Subtle findings in early LS, which may lead to
underdiagnosis, include preferential involvement of
adnexal structures with acanthosis and luminal
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 9
hyperkeratosis and hypergranulosis. A thickened
basement membrane may be appreciable, particularly
with a PAS stain.
■ The presence of dyskeratosis and parakeratosis,
hyperplasia, and/or basal cellular atypia (but less than
in dVIN [Chapter 2]) should be noted, one study finding
that >50% of LS cases associated with ISqCC had basilar
atypia.
■ The basal cells are typically p53+, usually with a
discontinuous pattern (unlike dVIN). In hypertrophic LS,
the suprabasilar cells may also be p53+. Sadalla et al.
found that p53 expression in LS did not predict
progression to SqCC.
Differential diagnosis
■ Lichen planus (LP) (also see Other Dermatoses).
• Genital involvement by LP can be difficult to
distinguish from early LS and the two lesions may be
synchronous. Day et al. suggest that when one lesion
is present or suspected the presence of the other
should be considered with separate biopsies from
morphologically distinct areas.
• Cytoid bodies, wedge-shaped hypergranulosis, basal
squamatization, and pointed rete ridges favor LP, but
these findings are less common than in extravulvar
LP.
■ dVIN (vs LS with basilar atypia) (Chapter 2).
■ Postradiation fibrosis. A history of radiation is obviously
helpful. This diagnosis is also favored in the presence of
more diffuse (vs band-like) fibrosis, atypical fibroblasts
and endothelial cells, and thick-walled vessels.
Behavior
■ Spontaneous remission may occur at puberty or
postpartum. In some cases, the lesions respond to topical
testosterone or corticosteroids.
■ There is strong evidence that LS is a premalignant
lesion; Davick et al. found that the proportion of women
with vulvar ISqCCs who had ever had a diagnosis of LS
was 36%. Longitudinal studies indicate that up to 5% of
cases of LS progress to vulvar ISqCC.
• Carli et al. (1995) found that women with LS have a
lifetime cumulative risk for vulvar ISqCC of 15%
compared to only 0.06% for women in the general
population.
• Up to 65% of cases of dVIN and ISqCC are associated
with synchronous LS.
• Some LS lesions are monoclonal and exhibit an
increased frequency of allelic imbalance.
• Regauer et al. (2002) found a monoclonal γ-T-cell
receptor rearrangement in LS-associated ISqCC, but
not in uncomplicated LS, suggesting that local
immune dysregulation in LS promotes development
of ISqCC.
• The frequency of p53 mutations and aneuploidy is
higher in LS associated with ISqCC than in
uncomplicated LS.
■ Patients with LS, particularly those with acanthotic or
atypical LS, should be monitored for the development of
SqCC.
Fig. 1.16 Squamous cell hyperplasia, NOS. The hyperplastic squamous
epithelium has no specific features.
SQUAMOUS CELL HYPERPLASIA, NOS
(Fig. 1.16)
■ The term ‘squamous cell hyperplasia, NOS’ (SCH),
which replaced the term ‘hyperplastic dystrophy’,
refers to epidermal hyperplasia not attributable to
more specific dermatologic disorders and lacking
dysplasia.
■ SCH has been found adjacent to 40% of SqCCs, in
20–50% of patients with a clinical diagnosis of vulvar
dystrophy, and in about a third of patients with LS.
■ A white plaque-like thickening of the involved skin may
be seen clinically. The thickened epidermis may show
hyperkeratosis or parakeratosis. There is normal
maturation from the basal to superficial layers. Atypia is
usually absent, and its presence should suggest dVIN
(Chapter 2). Mitotic figures, if present, are confined to
the basal and parabasal zones.
■ There is some evidence to suggest that SCH, if not
directly premalignant, may be an early stage in vulvar
carcinogenesis:
• The lesion may abut or merge with dVIN and/or
SqCC.
• Monoclonality and an increased expression of p53,
p53 mutations, and allelic imbalance occur in some
lesions, especially in those with synchronous SqCC.
Some lesions have contained HPV, yet all cases
studied by Santos et al. were p16-negative.
• Patients with SCH, like those with LS, need to be
monitored for the possible development of dVIN or
ISqCC.
OTHER DERMATOSES (Fig. 1.17)
■ Almost any dermatosis can involve the vulva (see review
by Greene and Dulaney and review of vulvar lichenoid
dermatitis by Lewin et al.), the most common being
10 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
Fig. 1.17 Lichen simplex chronicus.
lichen simplex chronicus, spongiotic dermatitis,
psoriasis, and lichen planus.
■ Lichen simplex chronicus is a common vulvar
dermatosis that can follow or coexist with a wide variety
of irritative and infectious factors.
• The clinical manifestations include pruritus and
burning and a leathery skin with scaly plaques and
accentuated cutaneous markings.
• Microscopically there is psoriasiform hyperplasia
(with rete ridges that are thicker and more variable in
length than in psoriasis), hypergranulosis,
hyperkeratosis, and occasionally, focal parakeratosis.
The papillary dermis is thickened; collagen bundles
SQUAMOUS PAPILLOMATOSIS (Fig. 1.18)
■ Squamous papillomatosis (squamous
micropapillomatosis, vestibular papillomatosis) refers
to multiple, often countless, squamous papillomas
that typically involve the medial aspect of the labia
minora, vulvar vestibule, hymen, introitus, and
urethral meatus.
■ Women of reproductive age are typically affected. They
are usually asymptomatic, although occasionally there is
pruritus, burning, or dyspareunia. The lesions usually
regress spontaneously.
PIGMENTED LESIONS
■ Benign pigmented vulvar lesions, which occur in about
10% of women, often have atypical clinical and/or
histologic features that may suggest malignant
melanoma.
Fig. 1.18 Squamous papillomatosis. The squamous cells have clear
cytoplasm due to the presence of glycogen, but are not koilocytotic.
may be arranged vertically, parallel to the rete ridges.
Scattered dermal inflammatory cells may be present.
■ Vulvar (or vulvovaginal) lichen planus can be erosive
and lead to scarring and stenosis. Associated
pseudoepitheliomatous hyperplasia may rarely progress
to SqCC. The differential diagnosis between lichen planus
and lichen sclerosus is considered under the latter
heading. The differential between erosive lichen planus
and differentiated VIN is discussed under the latter
heading (Chapter 2).
■ ‘Vulvar acanthosis with altered differentiation’ is a lesion
often associated with vulvar verrucous carcinoma (see
latter heading in Chapter 2).
■ The etiology is unknown; most studies have not found
an association with HPV. A study finding a high
frequency of HPV included koilocytic lesions that most
would consider condylomas.
■ The papillomas are ~1 mm in diameter and 1–8 mm in
length and consist of bland, nonkeratinized,
glycogenated squamous epithelium and a fibrovascular
core. Absence of koilocytosis (a definitional feature in
most studies) and a low Ki-67 rate (staining confined to
basal layer) allow distinction from condyloma.
LENTIGO SIMPLEX AND MELANOSIS
(Fig. 1.19)
■ Lentigo simplex refers to a lesion exhibiting benign
epidermal hyperplasia, hyperpigmentation, and benign
melanocytic hyperplasia. The term ‘melanosis’ is most
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 11
Fig. 1.19 Vulvar melanosis.
commonly used to refer to similar hyperpigmented
lesions, with or without melanocytic hyperplasia, that
lack epidermal hyperplasia.
■ The lesions, which typically occur in Caucasians of
reproductive age, may have been longstanding.
Melanotic macules involve the labia, introitus, or
perineum. Lentigines are usually <5 mm, whereas areas
of melanosis may reach 2 cm.
■ Occasionally the features suggest or mimic lentigo
maligna or malignant melanoma, including
multifocality, an irregular margin, and variegated
pigmentation.
■ Microscopically, there is basilar hyperpigmentation and
basilar melanocytic hyperplasia without nesting or
atypia. However, as noted above, some lesions designated
‘melanosis’ have lacked melanocytic hyperplasia.
Acanthosis with elongation of rete pegs is present in
lentigines; dermal melanophages also may be present.
■ The differential is with malignant melanoma in situ that,
unlike lentigo or melanosis, exhibits transepidermal
nests of atypical melanocytes that may exhibit mitoses.
USUAL MELANOCYTIC NEVI
■ Vulvar nevi are only a third as common as the lesions
considered in the preceding section, being found in only
2–3% of women. Most resemble their extravulvar
counterparts.
FIBROEPITHELIAL POLYP
■ These lesions are most common in the vagina and are
discussed in Chapter 3.
■ Some vulvar melanocytic nevi overlie or are entrapped
by the sclerosis of lichen sclerosus and may resemble
persistent melanocytic nevi.
■ Michalova et al. described dVIN-like changes (atypical
basal keratinocytes) overlying anogenital melanocytic
nevi. These foci showed normal p53 immunoreactivity
in contrast to diffuse or null p53 staining in dVIN.
ATYPICAL GENITAL NEVI
■ Vulvar nevi with atypical features that differ from those
of the usual dysplastic nevus have been referred to as
‘atypical melanocytic nevi of genital type’ or ‘atypical
genital nevi’ (AGN). AGN may have striking
architectural and cytologic atypia, but are clinically
benign.
■ Gleason et al. found a median patient age of 26 (range,
6–54) years and no site predilection.
Microscopic features
■ A lentiginous or nested junctional component exhibits
variability in the size, shape, and position of the nests,
including a confluent band-like arrangement.
• In addition to the usual location at the rete tips, the
nests may be seen on the sides of rete or between the
rete and adnexal structures, often with a retraction
artifact around the nests and/or cellular dyscohesion
within the nests.
• Pagetoid involvement of the upper epidermis may
occur, but in contrast to melanoma, the lesional cells
are usually focal or multifocal rather than extensive
or diffuse, and lack cytologic atypia and lateral
extension. However, atypia of the cells in the
junctional component is present and was moderate to
severe in 80% of cases in the Gleason study.
■ An underlying, often large, common dermal nevus is
often present that is diffusely or focally covered by the
junctional component.
• The cells in the dermal component may show atypia,
but which is less common and less severe than that of
the junctional component; mitotic figures are rare
and maturation is typically present.
• A broad zone of dense fibrosis within the superficial
dermis is present in 40% of cases, but usually lacks
the distinctive lamellar pattern seen in dysplastic
nevi.
■ AGN must be distinguished from vulvar dysplastic nevi
and superficial spreading melanoma (see Clark et al. and
Gleason et al.).
12 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
CYSTS
BARTHOLIN’S DUCT CYST (Figs. 1.20–1.21)
■ Obstruction of the vestibular orifice of Bartholin’s
duct results in a cyst filled with secretions. The usual
presentation is a lateral introital mass that may be
asymptomatic or associated with dyspareunia.
■ The cysts are lined by squamous, transitional, mucinous,
ciliated, or flattened nonspecific epithelium. Acute and
chronic inflammation is often present. One cyst had
melanocytic colonization (Nigam et al.).
■ A location consistent with Bartholin’s origin (posterior
lateral to vaginal introitus) and/or normal Bartholin’s
gland acini adjacent to the cyst facilitate distinction from
cysts arising from minor vestibular glands (see below).
MUCINOUS AND CILIATED VESTIBULAR
CYSTS (Fig. 1.22)
■ These cysts typically present as a solitary (or
occasionally multiple), sometimes painful, subcutaneous
Fig. 1.20 Bartholin’s duct cyst.
Fig. 1.21 Bartholin’s duct cyst. The squamous lining of the cyst (top)
and normal Bartholin’s gland tissue (bottom) are seen.
mass on the inner surfaces of the labia minora in the
reproductive age group.
■ The cysts are usually <3 cm in size and are lined by a
single layer of columnar mucinous epithelium, ciliated
nonmucinous epithelium, squamous epithelium, or
admixtures thereof. The lining cells may be ER+ and
PR+.
■ The cysts have traditionally been presumed to arise from
the minor vestibular glands in the anterior and posterior
vestibule. To account for the typical location of the cysts,
Scurry et al. suggest that minor vestibular glands likely
also occur at the vulvar mucocutaneous junction (Hart’s
lines).
OTHER CYSTS
■ Vulvar epidermal inclusion cysts are common, and
usually within the labia majora. They are lined by
stratified squamous epithelium and filled with
keratinaceous debris.
■ Vulvar epidermal inclusion cyst formation may occur
following female genital mutilation. Reports have
documented cyst formation as a delayed late
complication, and these can present as large cysts that
may clinically mimic clitoromegaly or a neoplasm.
■ Rare mesothelial cysts derived from the canal of Nuck
(the incompletely obliterated processus vaginalis) are
usually found in the superior aspect of the labia majora
or the inguinal canal. They may be associated with, and
should be distinguished from, an inguinal hernia.
■ Rare mesonephric cysts occur in the lateral aspects of
the vulva and histologically resemble vaginal
mesonephric cysts (Chapter 3).
■ Rare vulvar cysts may arise from the mammary-like
glands in this site (see Other Non-neoplastic Lesions).
Fig. 1.22 Mucinous vestibular cyst.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 13
NONINFECTIOUS INFLAMMATORY LESIONS
VULVAR VESTIBULITIS
Clinical features
■ Vulvar vestibulitis (aka ‘provoked localized vulvodynia’
[PLV]) affects up to 15% of women in a general gynecologic
practice, who are typically of reproductive age.
■ The typical feature is point tenderness of the vulvar
vestibule in the absence of other identifiable causes;
dyspareunia is also usually present. Vulvar erythema is
seen in some cases. Munday et al., however, have
concluded that the clinical features are nonspecific and
part of a continuum within the general population.
■ The etiology is unknown and possibly multifactorial.
HPV is usually absent or present with a frequency
similar to that of control patients.
■ Proposed pathogenetic factors include an increased
number of vulvar nerve fibers, hypersensitivity to
seminal fluid, deficiency of interferon-α, deficient ER
expression, and enhanced synthesis of proinflammatory
cytokines produced by vestibular fibroblasts.
Pathologic features (Fig. 1.23)
■ The histologic findings, which have varied between
studies, can support the diagnosis, but generally the
latter rests on the typical clinical findings.
■ Some studies have found a mild to severe chronic
inflammatory infiltrate (T lymphocytes, plasma cells, and
occasional B lymphocytes, mast cells, monocytes),
including lymphoid follicles, in the superficial dermis and
surrounding the vestibular glands and ducts.
■ Leclair et al. found that primary PLV specimens had more
CD4+ T cells than secondary PLV specimens and unaffected
controls, findings noteworthy given that CD4+ T cells are
recruited by infectious, allergic, or autoimmune triggers.
■ Bornstein et al. found an increase in subepithelial mast
cells, heparinase, and peripheral nerve fibers compared
to asymptomatic women.
Fig. 1.23 Vulvar vestibulitis. A minor vestibular gland shows squamous
metaplasia and chronic inflammatory cells in the surrounding stroma.
■ Squamous metaplasia of the vestibular ducts and
glands is an occasional finding, but may not be an
inherent feature of the disorder. Complete replacement
of the vestibular glands and ducts by squamous
epithelium producing an invagination or cleft was
considered a diagnostic feature in one study, whereas
two other studies found clefts to be uncommon and
difficult to distinguish from infoldings of surface
epithelium.
PLASMA CELL VULVITIS (ZOON’S VULVITIS)
(Fig. 1.24)
■ This idiopathic lesion typically presents with pruritus,
burning, and red, sometimes multiple, macules.
■ Histologic features are a predominantly plasmacellular
lichenoid infiltrate, a thinned epidermis, flattened rete
ridges, absence of the granular/keratin layers, spongiotic
parabasal keratinocytes with spindled horizontal nuclei
(‘lozenge keratinocytes’), and prominent dermal blood
vessels with hemorrhage and hemosiderin.
■ The differential includes syphilis, lichen planus, and
other chronic dermatoses.
GRANULOMATOUS VULVITIS AND VULVAR
INVOLVEMENT BY CROHN’S DISEASE
(Fig. 1.25)
■ Isolated granulomatous vulvitis is idiopathic and likely
the vulvar counterpart of granulomatous cheilitis;
occasional patients have both lesions.
■ It occurs over a wide age range and usually presents as a
labial mass or hypertrophy. Histologically, there is edema,
fibrosis, lymphangiectasia, a mononuclear infiltrate, and
non-necrotizing granulomas with giant cells.
Fig. 1.24 Plasma cell vulvitis.
14 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
Fig. 1.25 Granulomatous vulvitis.
■ More common than isolated granulomatous vulvitis, but
identical histologically, is vulvar involvement by Crohn’s
disease.
• There is usually a history of or synchronous
intestinal Crohn’s disease; rarely the vulvar
involvement precedes bowel involvement.
• Patients presenting with granulomatous vulvitis
therefore need to be evaluated for Crohn’s disease.
BEHÇET’S DISEASE
■ Behçet’s disease is a systemic vasculopathy that is most
frequent in Japan and eastern Mediterranean countries.
The mean age at onset is in the third decade; there is a
slight male predominance.
■ The disease is diagnosed by the presence of oral
ulceration and any two of genital ulceration, skin lesions
(pustules or erythema nodosa-like lesions), and eye
lesions (uveitis or retinal vasculitis). Synovitis and
meningoencephalitis may also occur.
■ The vulvar (and oral) ulcers are of minor or major
aphthous or herpetiform type. Major aphthous ulcers,
which may lead to gangrene, heal by scarring, but are
often followed by new ulcers.
■ A necrotizing neutrophilic or lymphocytic vasculitis can
involve all calibers and types of dermal and
subcutaneous vessels and be accompanied by mural
fibrin deposits, mural necrosis, and thrombosis.
FLORID REACTIVE LYMPHOID
HYPERPLASIA (LYMPHOMA-LIKE LESION)
(Fig. 1.26)
■ This rare lesion has clinicopathologic features like those
in the cervix (Chapter 4). One vulvar case was associated
with infectious mononucleosis and presented as a 1 cm
crusted lesion on the labium minus.
Fig. 1.26 Florid reactive lymphoid hyperplasia. Vulvar biopsy from a
patient with malaise shows ulceration and marked inflammatory
infiltrate (left). High-power view of the infiltrate shows large lymphoid
cells, scattered immunoblasts with prominent nucleoli, and apoptosis
(right). This patient was subsequently documented to have infectious
mononucleosis. (Courtesy of Dr. Judith A Ferry)
GRAFT-VERSUS-HOST DISEASE (GVHD)
■ The vulvovaginal area is the most common site in the
female genital tract for GVHD (a complication of bone
marrow transplantation).
■ The most frequent symptoms include vulvovaginal
dryness, discharge, discomfort, ulceration, scarring, a
narrowed or obliterated introitus and/or vagina, and
dyspareunia that develop at a mean interval of 10
months after transplantation.
■ Vulvar biopsies show changes similar to cutaneous
GVHD, including ulceration, apoptotic bodies in the
epidermal basal layer, and chronic inflammation.
Vaginal biopsies show inflammation, apoptotic bodies,
and fibrosis. The cervical mucosa and endometrial
glands may also show apoptotic bodies.
■ These patients are also at higher risk for condylomas and
HPV-related neoplasms.
SJÖGREN AND NON-SJÖGREN SICCA
SYNDROMES
■ Most women with these syndromes have vulvar
involvement with vulvovaginal dryness, dyspareunia,
and pruritis.
■ Bongi et al. found that vulvar biopsies typically showed a
mild to moderate, sometimes band-like, lymphocytic
infiltrate (predominantly T lymphocytes) within the
superficial lamina propria. The squamous epithelium
was sometimes acanthotic but otherwise unremarkable.
■ There was no correlation between the findings in the
vulva and the salivary glands.
LIGNEOUS VULVITIS
■ See Chapter 4.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 15
REACTIVE LESIONS
REACTIVE ATYPIA AND MULTINUCLEATED
KERATINOCYTES (Figs. 1.27–1.28)
■ Nonspecific reactive changes within the vulvar epidermis
include loss of epithelial maturation and nuclear atypia
that may suggest VIN (Chapter 2). Prominent
inflammation, spongiosis, lack of mitoses, ki-67 staining
confined to the lower third of the epithelium, and
negative staining for HPV and p16 favor a reactive
lesion.
■ Multinucleated keratinocytes in vulvar and extravulvar
skin may reflect a defect in nuclear division in
persistently irritated skin.
NODULAR FASCIITIS (Figs. 1.29–1.30)
■ This lesion occurs over a wide age range (7–51 years),
typically presenting as a painless, subcutaneous labial
Fig. 1.27 Reactive atypia of vulvar epidermis.
Fig. 1.29 Nodular fasciitis of vulva, sectioned surface.
mass usually <4 cm in size. Local excision is usually
curative, although rare lesions recur locally. The
histologic features are as at other sites.
■ Initial misdiagnosis is common, potentially leading to
inappropriate treatment. The differential diagnosis
includes other reactive lesions such as postoperative
spindle cell nodule (Chapter 3) and soft tissue tumors,
including sarcoma (Chapter 2).
POSTOPERATIVE SPINDLE CELL NODULE
■ Rare vulvar examples of this lesion have been reported
(Chapter 3).
Fig. 1.28 Multinucleated vulvar keratinocytes (see text).
Fig. 1.30 Nodular fasciitis.
16 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
LESIONS RELATED TO LYMPHEDEMA,
IMMOBILIZATION, AND REPETITIVE
TRAUMA (Figs. 1.31–1.34)
■ Vulvar lymphedema, often due to obesity and/or
immobilization, may lead to vulvar enlargement that
can be massive. In other cases there is isolated
hypertrophy of the labia minora.
• Findings may include giant cells, dermal fibrosis,
vascular proliferation, lymphangiectasia, perivascular
lymphocytes and plasma cells, and reactive epidermal
changes. Lawrance et al. reported a case complicated
by vulvar lymphangiomas.
• Features favoring vulvar lymphedema vs aggressive
angiomyxoma include obesity or immobilization,
bilaterality, superficial location, reactive epidermal
changes, perivascular inflammation, and absence of
Fig. 1.31 Massive localized lymphedema. A large yellow mass is
traversed by fibrous septa.
Fig. 1.33 Massive localized lymphedema. Small stellate cells without
atypia in an edematous background is seen on higher power.
the following: lesional vessels of varying caliber,
perivascular smooth muscle, alcianophilic stroma,
and ER+ cells.
■ A vulvar lesion in a paraplegic woman, interpreted as
ischemic fasciitis (atypical cubital fibrodysplasia),
showed ulceration, fibrinoid necrosis, and a proliferation
of small vessels and atypical fibroblasts.
■ Unilateral solitary nodules up to 6 cm in size occur in
the labium majus in competitive cyclists (‘cyclist’s
nodule’) or equestrians. One lesion recurred.
• There is a haphazard admixture of bland
spindle-shaped fibroblasts, blood vessels (that may
include dilated lymphatics), nerves, fat, and
keloid-like foci. Other findings may include epithelioid
or plasmacytoid myofibroblasts, lymphocytes, fat
necrosis, and elastic fibers.
• The lesional cells are ER+ and the epithelioid cells are
SMA+.
Fig. 1.32 Massive localized lymphedema. The mass is composed of a
proliferation of bland spindled cells set in a focally edematous fibrous
matrix.
Fig. 1.34 Massive localized lymphedema. Prominent small blood
vessels some of which have conspicuous cuffs of smooth muscle.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 17
OTHER NON-NEOPLASTIC LESIONS
ENDOMETRIOSIS
■ Endometriosis is covered in detail in Chapter 19, but
specific comments related to vulvar endometriosis are
included here.
■ Vulvar endometriosis typically occurs within a surgical
site (episiotomy, Bartholin gland excision) due to
menstrual or intraoperative implantation of endometrial
tissue.
■ The usual presentation is a vulvar nodule, or
occasionally a sizable mass, sometimes with catamenial
symptoms, or rarely dyspareunia. Occasional cases occur
in adolescents. The gross and microscopic findings are
similar to those of endometriosis in general.
■ Rarely, neoplasms (clear cell adenocarcinoma,
endometrial stromal sarcoma) have arisen within vulvar
endometriosis.
MULTINUCLEATED STROMAL GIANT CELLS
(Fig. 1.35)
■ MSGCs, like those in fibroepithelial polyps (Chapter 3),
are a common incidental microscopic finding within the
loose subepithelial stroma of the lower FGT, especially
the vulva, being present in as many as ~75% of such
specimens.
■ MSGCs have eosinophilic cytoplasm with tapering
cytoplasmic processes and multiple nuclei (often in a
wreath-like arrangement) that are mitotically inactive,
and a vimentin+/cytokeratin−/desmin− immunoprofile.
ADENOSIS
■ Rare cases of introital adenosis of tuboendometrioid type
have occurred in Stevens–Johnson syndrome or after
Fig. 1.35 Multinucleated stromal giant cells. Note wreath-like
arrangement of the nuclei in some cells.
CO2 laser treatment; there has been no association with
in utero DES exposure.
■ A case of vulvar adenosis (‘mucinous metaplasia’)
appeared as a 1 cm depressed red periclitoral lesion in a
60-year-old. Microscopic examination showed
replacement of the squamous epithelium by columnar
mucinous cells.
ECTOPIC BREAST TISSUE AND RARER
ECTOPIAS (Fig. 1.36)
■ Vulvar breast tissue and mammary-type lesions have
been traditionally considered to arise from the
embryonic milk line; an origin from anogenital
mammary-like glands is currently favored.
• Ectopic breast tissue usually forms a unilateral or
bilateral, solid to cystic, subcutaneous mass on the
labium majus; rarely there is an associated nipple.
The lesions present at puberty or during pregnancy,
sometimes with postpartum regression.
• Microscopic findings have included pregnancy-related
lactational changes, fibrocystic changes, sclerosing
adenosis, lipomatous change, pseudoangiomatous
stromal hyperplasia, and benign or malignant tumors
(Chapter 2).
■ Rare vulvar cases of prostatic-type tissue have
included a 4.5 cm mass considered of Skene’s gland
origin.
■ A 6 cm vulvar mass (‘choristoma’) was comprised of
salivary gland tissue and a minor component of
cartilage and respiratory epithelium.
■ Several cases of intestinal (or enteric) heterotopia have
been reported in which the epidermis was replaced by
colonic mucosa, with CDX2+ cells in one case. In
another case, a vulvar lesion resembled a juvenile
colonic polyp.
Fig. 1.36 Ectopic breast tissue with lactational changes in the vulva of
a pregnant woman.
18 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
NODULAR HYPERPLASIA OF BARTHOLIN’S
GLAND (Fig. 1.37)
■ This lesion has occurred in women of reproductive and
postmenopausal age as a solid or solid and cystic,
nonencapsulated mass usually <5 cm in size. It may be
related to duct obstruction. None of the lesions has
recurred, even after incomplete excision.
■ A proliferation of benign mucinous acini has an irregular
lobulated contour with maintenance of the normal
relationship of ducts to acini, in contrast to adenomas
(see Benign Epithelial Tumors). Inflammation, cysts, and
squamous metaplasia of the ducts are often present.
VARICES
■ Vulvar varices may occur alone or associated with leg varices,
venous malformations (Klippel–Trenaunay–Weber and
Parkes–Weber syndromes), or pelvic congestion syndrome.
■ The lesions vary from small protrusions, mainly in the
labium majus, to large vulvar or perivulvar masses, and
can be misdiagnosed clinically as a Bartholin duct cyst.
AMYLOIDOSIS
■ Vulvar amyloidosis is rarely the presenting manifestation
of systemic amyloidosis, and may clinically mimic cancer.
■ Quddus et al. studied 26 cases of localized vulvar
amyloidosis and compared them with vulvar
involvement by systemic amyloidosis.
• The amyloid in the localized cases stained for Congo
Red, CK5, and CK14. As the cytokeratins were absent
BENIGN EPITHELIAL TUMORS
PAPILLARY HIDRADENOMA
(HIDRADENOMA PAPILLIFERUM) AND
OTHER APOCRINE TUMORS (Figs. 1.38–1.39)
■ Vulvar examples of papillary hidradenoma likely arise
from anogenital mammary-like glands that occasionally
abut the tumor.
• The tumors usually present in reproductive or
postmenopausal women as a painless vulvar nodule,
usually on the labium majus or minus, less commonly
the fourchette or clitoris.
• Most are <2 cm in size; rarely they are multiple. In
one study, 55% were cystic and 17% were ulcerated.
• Microscopically, a well-circumscribed to slightly
infiltrative, complex proliferation of papillae, tubules,
cysts, and solid areas are composed of epithelial and
myoepithelial cells.
• The apocrine and nonapocrine epithelial cells may
exhibit mild atypia, stratification, and occasional
mitoses. The myoepithelial cells, which typically
Fig. 1.37 Nodular hyperplasia of Bartholin’s gland.
in vulvar involvement by systemic amyloidosis, they
were presumed to be of epidermal origin.
• 85% of the localized cases were associated with ISqCC
or HSIL; the remaining cases were associated with
LSIL, seborrheic keratosis, or squamous hyperplasia.
MISCELLANEOUS OTHER LESIONS
■ Rare vulvar examples of sebaceous hyperplasia,
rheumatoid nodule, calcinosis, lymphoid hamartoma,
sclerosing lipogranuloma, and arteriovenous
malformation have been reported.
■ Roma et al. reported a series of cases of vulvar
sebaceous hyperplasia; none had evidence of the
Muir–Torre syndrome or MMR protein loss.
subtend the epithelial cells, are usually flattened and
inconspicuous, but may be larger and polygonal with
clear cytoplasm.
• Unusual features include sebaceous or squamous
differentiation; foci resembling sclerosing adenosis,
ductal adenoma, or sclerosing intraductal papilloma
of the breast; numerous mitotic figures;
inflammation; and calcification.
• Goto et al. found PIK3CA and AKT1 are mutated in
29% and 14% of tumors, respectively, further
supporting their origin from mammary-like glands.
• Rare cases of malignant transformation have included
adenocarcinoma in situ, intraductal apocrine carcinoma,
and a rapidly fatal adenosquamous carcinoma.
• The differential diagnosis is with intraductal
papilloma arising in ectopic breast tissue (see below).
However, Konstantinova et al. consider papillary
hidradenoma the cutaneous counterpart of
mammary intraductal papilloma.
■ Other benign apocrine vulvar tumors include apocrine
cystadenoma, papillary apocrine fibroadenoma, apocrine
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 19
Fig. 1.38 Hidradenoma papilliferum. Papillary formations with
slit-like spaces ramify within the subepithelial stroma.
Fig. 1.40 Syringoma. Relatively uniform small tubules are scattered
throughout the dermis without alteration of the surrounding stroma
(top). The tubules lack cytologic atypia (bottom).
Fig. 1.39 Hidradenoma papilliferum. The glands and papillae are lined
by an inner layer of columnar cells and outer layer of myoepithelial
cells.
Fig. 1.41 Pleomorphic adenoma (benign mixed tumor). The neoplasm
has a lobulated architecture (left) and is composed of small tubules
within a conspicuous myxoid stroma. Note the bland cytologic features
of the cells lining the tubules (right).
tubular adenoma, pigmented apocrine hamartoma,
poroma, and spiradenoma.
OTHER BENIGN TUMORS OF SKIN
APPENDAGE ORIGIN (Figs. 1.40–1.41)
■ Tumors of sweat gland origin include syringoma (rarely
with deep dermal extension) including mixed tumors of
eccrine type, clear cell hidradenoma, poroid
hidradenoma, and benign mixed tumors (pleomorphic
adenomas). The mixed tumors may also arise from
myoepithelial cells in Bartholin’s gland, ectopic breast
tissue, or mammary-like glands.
■ Tumors of hair follicle origin (trichogenic tumors)
include pilar tumor (proliferating trichilemmal tumor,
trichilemmoma), trichoepithelioma, trichoblastic
fibroma, trichofolliculoma, keratoacanthoma, inverted
follicular keratosis, polomatricoma, and sebaceoma.
20 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
Fig. 1.42 Seborrheic keratosis.
• Regauer and Nogales compared vulvar trichogenic
tumors (mean age, 65 years) and vulvar basal cell
carcinomas (BCCs) (mean age, 78 years). The former
formed a plaque or nodule, and unlike BCCs, had an
organized mesenchymal component and lacked
ulceration and clefting at the epithelial–stromal
interface. BCCs lacked trichogenic differentiation and
had a mucinous or granulation tissue-like stroma.
• As in extravulvar sites, vulvar keratoacanthoma and
inverted follicular keratosis occasionally can be
confused with SqCC.
• Three cases of vulvar trichofolliculoma were
associated with synchronous high-grade VIN; two
were initially misdiagnosed as invasive carcinoma.
SEBORRHEIC KERATOSIS (Fig. 1.42)
■ Bai et al. found HPV (usually HPV 6) in 72% of cases of
vulvar seborrheic keratosis (SK), leading to the
designation ‘condyloma with features of SK’. MIB1
helped identify those lesions that were most likely to
harbor HPV. In a similar study, Reutter et al. found HPV
in only 14% of vulvar SKs; there were no histologic
differences between those with and without HPV.
BENIGN MAMMARY-TYPE TUMORS (Fig. 1.43)
■ Benign vulvar mammary-type tumors, which have arisen
or presumed to arise from anogenital mammary-like
glands, have included hamartomas, fibroadenomas,
phyllodes tumors, and intraductal papillomas.
■ Rajguru et al. reported a well-circumscribed vulvar
tumor resembling microglandular adenosis of the breast
but with a prominent chondromyxoid stroma.
BENIGN TUMORS OF BARTHOLIN’S GLAND
AND MINOR VESTIBULAR GLANDS
■ Rare adenomas and adenomyomas of Bartholin’s gland
have, in contrast to nodular hyperplasia (see
Fig. 1.43 Fibroadenoma of mammary type.
corresponding heading), exhibited a haphazard
proliferation of acini and tubules with loss of the
normal duct-to-acini relationship. Rare adenoid
cystic carcinomas have arisen from Bartholin’s
gland adenomas; one was mixed with an
epithelial-myoepithelial carcinoma.
■ Two benign vulvar mixed tumors were considered
of probable Bartholin’s gland origin. Another
report described a papilloma arising in a Bartholin’s
cyst.
■ Rare adenomas (or nodular hyperplasias) of minor
vestibular glands, which are typically an incidental
finding in tissue removed for vestibulitis, consist of a
proliferation of small glands lined by mucinous
columnar cells.
MYOEPITHELIOMA-LIKE TUMORS
■ Yoshida et al. described nine such tumors involving the
vulvar subcutis or adjacent sites in women 24–65 years
of age. The tumors were 2–7.7 cm in size, well
circumscribed, focally encapsulated, and lobulated.
Three tumors recurred locally; none were clinically
malignant.
■ The epithelioid to spindled tumor cells had amphophilic
cytoplasm and uniform nuclei with vesicular chromatin
and visible nucleoli. The stroma was focally to
extensively myxoid. In the nonmyxoid areas the
tumor cells were in sheets or storiform arrangements
but were singly disposed or loosely cohesive in the
myxoid areas.
■ The typical immunoprofile was vimentin+/EMA+/ ER+/
actin+/CK−/SMARCB1 deficient. None showed EWSR1,
FUS, or NR4A3 rearrangements.
TUBULOVILLOUS ADENOMA
■ An enteric-type tubulovillous adenoma of the vulva
occurred in 66-year-old woman; a similar rectal tumor
had been removed 6 months previously.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 21
BENIGN AND LOCALLY AGGRESSIVE MESENCHYMAL TUMORS OF THE LOWER
GENITAL TRACT
■ A variety of mesenchymal tumors composed of bland
fibroblastic and myofibroblastic cells occur within the
soft tissues of the lower FGT. These tumors can be
diagnostically problematic because of their overlapping
histologic and immunohistochemical features.
■ At least some of the tumors likely arise from indigenous
hormonally responsive fibroblastic or myofibroblastic
stromal cells that are variably positive for vimentin,
smooth muscle markers, CD34, ER, and PR.
■ Fibroepithelial polyps, which may be histogenetically
related to the tumors in this group, are considered in
Chapter 3 as they are most common in the vagina.
AGGRESSIVE ANGIOMYXOMA
Clinical features
■ Over 90% of these tumors (AAs, deep angiomyxoma)
occur in the reproductive era typically as a mass that is
Fig. 1.44 Aggressive angiomyxoma. The tumor is poorly
circumscribed and glistening.
Fig. 1.46 Aggressive angiomyxoma. Note admixture of thin- and thick-
walled vessels of varying caliber within a sparsely cellular stroma.
vulvar, suburethral, perineal, vaginal, inguinal, gluteal,
ischiorectal, retroperitoneal, or combinations thereof.
The initial clinical impression is often that of a
Bartholin’s cyst or hernia.
■ AAs are often much larger and deeper than initially
appreciable on pelvic examination; imaging studies
may help delineate the mass. Large tumors may fill the
pelvis, tending to displace rather than invade pelvic
viscera.
Pathologic features (Figs. 1.44–1.47)
■ The typically bulky, rubbery, and solid tumors have a
lobulated to poorly circumscribed contour. The cut
surface is usually glistening, gelatinous, and
homogeneous, with occasional small cysts and focal
hemorrhage.
■ AAs are sparsely cellular with small oval, spindle, and
stellate cells interspersed in a loose edematous to weakly
myxoid stroma.
Fig. 1.45 Aggressive angiomyxoma. The tumor infiltrates adipose
tissue.
Fig. 1.47 Aggressive angiomyxoma. Tumor cells with scanty
cytoplasm and bland nuclear features are widely separated by a
sparsely cellular stroma.
22 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
■ The stroma typically contains delicate collagen fibrils
and numerous, haphazardly scattered, variably sized
vessels with thin to thick walls; the latter may be
hyalinized or muscular. Perivascular cuffs of collagen
and bundles of smooth muscle are common; the latter
may also occur unrelated to vessels.
■ The tumor cells have scanty pale eosinophilic cytoplasm,
small uniform nuclei, and small indistinct nucleoli; rare
cells are multinucleated. Mitotic figures are absent or
rare.
■ The intercellular component stains weakly with Alcian
blue and colloidal iron. Extravasated erythrocytes and
sparse mast cells are commonly present.
■ AAs lack a capsule and infiltrate the surrounding soft
tissue, often with entrapment of fat, skeletal muscle, and
nerves.
■ Unusual findings include foci resembling
angiomyofibroblastoma (see below), focal cellularity,
fibrotic areas (especially in recurrences), and admixed
endometriosis.
■ The tumor cells are vimentin+ and stain variably for
smooth muscle markers (desmin, SMA, MSA), CD34,
and CD44. Nuclear staining for ER and PR is usually
present. Unlike most other vulvovaginal mesenchymal
tumors, nuclear expression for HMGA2 is found in 50%
of the tumors.
■ Rearrangements of the HMGA2 locus on chromosome
12 are found in a third of tumors; in some such cases
chromosomal translocations have been identified.
■ McCluggage et al. found strong diffuse expression of
HMGA2 by immunohistochemistry in 10 of 12 AA.
However, while staining appears sensitive and may be of
value in primary diagnosis as most lesions that mimic
AA are negative, it is not specific as expression may be
seen in other mesenchymal tumors, such as leiomyomas.
Behavior
■ AAs are typically indolent but have a tendency to recur
locally because of frequent incomplete excision. Early
studies found a ~40% recurrence rate vs ~10% in more
recent series.
Fig. 1.48 Angiomyofibroblastoma, showing a well-circumscribed
mass.
■ The recurrences may appear many years
postoperatively and multiple recurrences are
common. Fibrotic recurrent tumor may be difficult to
differentiate from normal or scar-related connective
tissue.
■ Only one well-documented case with hematogenous
spread has been reported (Blandamura et al.), in which
fatal pulmonary metastases appeared after multiple local
recurrences.
■ GnRH-agonists or aromatase inhibitors can successfully
treat unresectable primary or recurrent tumor in some
cases.
Differential diagnosis
■ Angiomyofibroblastoma (see next heading).
■ Superficial angiomyxoma (cutaneous myxoma) (see
corresponding heading). These tumors differ from
AAs by their superficial location, small size,
circumscription, absence of thick-walled muscular
vessels, presence of neutrophils, and nonreactivity for
desmin, ER, and PR.
■ Myxoma, spindle cell lipoma, myxoid neurofibroma,
fibroepithelial polyp, fibromatosis, myxoid liposarcoma,
myxoid smooth muscle tumors, embryonal
rhabdomyosarcoma (sarcoma botryoides), and myxoid
malignant fibrous histiocytoma.
• These tumors often have differing gross features, and
aside from a myxoid stroma, all lack AA’s
characteristic histologic appearance, including its
distinctive vascular component.
• Additionally, myxoid sarcomas usually contain
nonmyxoid areas and cells with nuclear
pleomorphism and mitoses.
ANGIOMYOFIBROBLASTOMA (Figs. 1.48–1.52)
■ These tumors (AMFs) occur in the reproductive and
postmenopausal eras. A painless vulvar, or less
commonly, vaginal mass <5 cm in size is usually present
that may clinically mimic a Bartholin’s cyst.
Fig. 1.49 Angiomyofibroblastoma, low-power view. Note well-
circumscribed border.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 23
Fig. 1.50 Angiomyofibroblastoma. Note the epithelioid cells, many of
which are perivascular.
Fig. 1.52 Angiomyofibroblastoma, ‘lipomatous’ variant. Perivascular
epithelioid tumor cells lie within adipose tissue, which was abundant in
this tumor.
■ AMFs are well circumscribed and composed of
hypercellular zones alternating with hypocellular
edematous and fibrous zones in which numerous
small-to-medium sized, thin-walled arborizing vessels
(predominantly capillaries) are irregularly distributed.
Perivascular fibrosis is common.
■ The tumor cells, which may be spindled, oval,
plasmacytoid (due to eccentric nuclei), or epithelioid
(with eosinophilic cytoplasm), are separated by wavy
strands or thick bundles of collagen. The cells form
perivascular aggregates, nests, or cords, or are loosely
dispersed in the hypocellular areas. Scattered
lymphocytes and mast cells are common.
■ Fat may be present and is occasionally prominent
(lipomatous variant), in some cases accounting for >90%
of the tumor.
■ The nuclear features are typically bland, but in 40% of
the cases rare nuclei are enlarged and hyperchromatic.
Fig. 1.51 Angiomyofibroblastoma, ‘lipomatous’ variant. Note the
scattered yellow areas, which correspond to adipose tissue.
Occasional cells are multinucleated. Mitotic figures are
absent or rare.
■ The cells typically stain for vimentin and desmin,
frequently for ER and PR, and occasionally for actin and
CD34. HMGA2 reactivity has not been demonstrated.
Unlike cellular angiofibromas and myofibroblastomas
(see corresponding headings), Magro et al. found no loss
of FOXO1(13q14) in AMFs.
■ AMFs are benign but occasionally recur after local
excision. One tumor consisting of typical AMF and
high-grade sarcoma (‘angiomyofibrosarcoma’) recurred
2 years later as pure sarcoma (Nielsen et al., 1997).
Differential diagnosis
■ Aggressive angiomyxoma. In contrast to this tumor,
AMF is circumscribed and focally more cellular, has
more blood vessels (usually without thick walls), and has
plump to epithelioid tumor cells that are often
perivascular. Rare hybrid neoplasms have features of
both tumors.
■ Cellular angiofibroma. Features favoring this diagnosis
include greater cellularity, numerous vessels with
hyalinized walls, and an absence of perivascular
epithelioid cells.
■ AMF-like stromal reaction. A reactive lesion resembling
AMF has been described in prolapsed fallopian tubes (see
Chapter 11).
■ Lipomatous tumors. The lipomatous variant of AMF
should be excluded by thorough sampling before
considering a vulvar lipomatous tumor. ER positivity
favors AMF.
SUPERFICIAL ANGIOMYOXOMA
(CUTANEOUS MYXOMA) (Figs. 1.53–1.55)
■ Patients with these tumors, which are more common in
extragenital sites, are usually of reproductive age (mean,
21 years) who present with a slowly growing painless
24 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
Fig. 1.53 Superficial angiomyxoma. Irregular tongues of myxoid
tissue are conspicuous.
Fig. 1.55 Superficial angiomyxoma. Small bland spindle to stellate
cells lie within a myxoid matrix and a few delicate capillaries are seen.
mass. Multiple extragenital tumors have been a
manifestation of Carney’s complex, an association not
yet found in vulvar tumors.
■ The tumors are usually <5 cm in size,
well-circumscribed, nodular or multinodular or polypoid
masses that involve skin or subcutis, with a gelatinous
sectioned surface.
■ Microscopic examination reveals sparsely cellular
nodules of spindle to stellate cells, delicate capillary-like
vessels, and an alcianophilic myxoid matrix. The tumor
cells have bland to mildly pleomorphic nuclei, with
occasional multinucleated cells; mitotic figures are rare
to absent.
■ Other findings include inflammatory cells, especially
neutrophils, and in some tumors, entrapped cystic
epithelial inclusions likely of adnexal origin.
■ The tumor cells are usually reactive for vimentin, CD34,
and less commonly, actin, S100 protein, and Factor
XIIIa.
Fig. 1.54 Superficial angiomyxoma. Cystic epithelial inclusions are a
common finding.
■ The tumors are benign but 30–40% of them recur due
to incomplete excision, sometimes many years later.
■ The differential diagnosis is with aggressive angiomyxoma
(see above). The stroma of superficial angiomyxoma is
much more myxoid than that of aggressive angiomyxoma.
CELLULAR ANGIOFIBROMA (Figs. 1.56–1.57)
■ These tumors occur in the reproductive or
postmenopausal eras as a superficial mass, most
commonly in the vulva; rare tumors have arisen in the
vagina, paravaginal region, perineum, inguinal region,
or urethra. They are successfully treated by local
excision; one recurred locally.
■ The usually well-circumscribed tumors are ≤12 cm in
size (median 2.8 cm in one series) and have a solid,
white, tan, or grey sectioned surface.
■ Microscopic features of typical cellular angiofibromas:
• A cellular proliferation is comprised of spindle cells in
short intersecting fascicles; numerous small to
medium-sized, thick-walled, often hyalinized, blood
vessels; and short wispy collagen bundles. The spindle
cells have scanty eosinophilic cytoplasm, bland
nuclei, and rare mitoses.
• Fat is present in ~25% of cases but usually accounts
for <5% of the tumor. Hypocellular areas of edema,
myxoid change, or hyalinization may be present.
• Uncommon findings include an infiltrative border,
absence of thick-walled vessels, dilated
hemangiopericytomatous vessels, vague nuclear
palisading, mild cytologic atypia, multinucleated
(symplastic) cells, numerous mitoses (up to 11 mf/10
hpf), and stromal lymphoid aggregates.
• The spindle cells stain for vimentin, CD34, SMA, and
desmin in approximately 100%, 50%, 20%, and 10%
of cases, respectively, suggesting a fibroblastic rather
than a myofibroblastic phenotype. Nuclear staining
for ER and/or PR is found in 50% of the tumors.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 25
Fig. 1.56 Cellular angiofibroma. A well-circumscribed cellular
proliferation of spindled with interspersed small to medium-sized
vessels lies within the superficial dermis.
• Two tumors contained FOXO1(13q14) deletions,
suggesting a link with spindle cell lipoma and
extramammary myofibroblastoma.
■ Chen and Fletcher found that ~8% of vulvar cellular
angiofibromas contained foci of severe atypia or
sarcomatous transformation.
• In those with severe atypia, the atypical cells were
usually scattered throughout the tumor but in one
tumor were localized to a discrete nodule.
• Sarcomatous transformation took the form of
atypical lipomatous tumor, pleomorphic liposarcoma,
or nonspecific pleomorphic sarcoma.
• The atypical and sarcomatous cells were multifocally
or diffusely p16+ in contrast to absent staining in the
typical areas of the tumor.
• Limited clinical follow-up found no recurrences or
metastases.
Differential diagnosis
■ Aggressive angiomyxoma (AA). AA is usually larger,
deeper, and has infiltrative borders, diffuse
hypocellularity, less prominent hyalinized blood vessels,
and a more myxoid, less fibrous, intercellular
component. A desmin+/CD34− phenotype favors AA.
■ Angiomyofibroblastoma (AMF). AMF has more variable
cellularity, perivascular epithelioid or plasmacytoid
tumor cells, and a predominance of thin-walled vessels.
A desmin+/CD34− phenotype favors AMF.
■ Spindle-cell lipoma. These tumors are rare in the vulva
and contain CD34+ spindle cells similar to those of
cellular angiofibroma. However, unlike most of the latter,
they typically contain a prominent adipocytic
component and inconspicuous thin-walled vessels.
■ Solitary fibrous tumor (SFT) (see below). SFTs are rare in
the FGT. They have overlapping features with cellular
Fig. 1.57 Cellular angiofibroma. A cellular proliferation of
monotonous bland ovoid to spindle cells contains many small and
medium-sized vessels, some with thick walls.
angiofibroma, including the presence of fat and CD34
and STAT6 positivity. SFTs, however, usually have more
variable cellularity, dense hyaline collagen bundles, areas
of hyalinization, and hemangiopericytoma-like vessels.
SUPERFICIAL MYOFIBROBLASTOMA
■ The patients have been aged 23–80 (median 54) years,
who typically present with a superficial polypoid or
nodular mass, usually in the vagina, or uncommonly in
the cervix or vulva. Occasionally there is a history of use
of tamoxifen or other hormonal preparations. One
vulvar tumor recurred locally 9 years after incomplete
excision.
■ The tumors range up to 6.5 cm in size (mean, 2.3 cm);
one patient had two synchronous vaginal lesions. The
well-circumscribed but unencapsulated tumors are
covered by unremarkable or hyperplastic squamous
epithelium that is usually separated from the tumor by a
Grenz zone.
■ Microscopic examination reveals a moderately cellular
proliferation of bland, mitotically inactive, ovoid, spindle,
or stellate cells, often with a wavy nucleus, separated by
a finely collagenous stroma.
■ A patternless arrangement of the spindle cells usually
predominates, but lace-like, fascicular and storiform
patterns, as well as myxoid, edematous, or hyalinized foci
with thick dense collagen bundles are also common. The
deep aspects of larger tumors are often hypercellular, and
may even suggest a small round blue cell tumor.
■ Thin-walled blood vessels, sometimes with perivascular
hyalinization, are often concentrated within the center
of the tumor. Larger tumors may contain occasional
thick-walled vessels.
26 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
■ The myofibroblastic immunoprofile includes usual
reactivity for vimentin, desmin, ER, and PR; staining for
CD34, CD99, CD10, SMA, bcl-2, and calponin is present
in some cases.
■ Using FISH, Magro et al. found monallelic deletion of
FOXO1 (13q14) in 3 of 5 vaginal tumors.
Differential diagnosis
■ Fibroepithelial polyp (Chapter 3). This lesion, unlike
myofibroblastoma, lacks an expansile nodular
appearance and a distinct margin, is usually less cellular,
often contains multinucleated stromal giant cells, and
lacks both a Grenz zone and a multipatterned
architecture. Distinction from cellular fibroepithelial
polyps is more difficult and the lesions may be part of a
spectrum.
■ Angiomyofibroblastoma. This tumor, unlike superficial
myofibroblastoma, typically contains perivascular
aggregates of epithelioid or plasmacytoid cells, and
usually lacks the multipatterned architecture of
myofibroblastoma. Their immunoprofiles are similar.
■ Aggressive angiomyxoma. These tumors, in contrast to
superficial myofibroblastomas, are usually more deeply
seated, have infiltrative borders, are more myxoid and
less cellular, and have blood vessels that are more
prominent and variable in size.
■ Cellular angiofibroma. These tumors are more diffusely
cellular than superficial myofibroblastomas, contain
many thick-walled vessels and sometimes fat, and
lesional cells that typically are desmin-negative.
■ Solitary fibrous tumor. This tumor has a consistent
STAT6+/CD34+/desmin− phenotype.
PREPUBERTAL VULVAR FIBROMA
(Figs. 1.58–1.59)
■ This tumor (PVF; aka ‘childhood asymmetric labium
majus enlargement’) usually presents as a painless,
Fig. 1.58 Prepubertal fibroma. The tumor is composed of hyalinized
fibrous tissue, adipose tissue, and blood vessels. (Courtesy of Dr.
Christopher Fletcher)
unilateral, subcutaneous vulvar mass (usually in the
labium majus) in girls 3–13 years of age. One
postmenopausal case has been reported.
■ PVFs are 2–8 cm in size and poorly circumscribed.
Microscopically, there is a hypocellular proliferation of
bland, mitotically inactive spindle cells that are separated
by a variably collagenous (short bundles of thick wavy
collagen), edematous, or myxoid matrix.
■ The lesional cells typically infiltrate and entrap
surrounding vessels, fat, and nerves, and may extend to
the epidermal–stromal interface.
■ The spindle cells are typically CD34+, but are negative
for SMA, desmin, and S100, suggesting a purely
fibroblastic lesion.
■ About 30% of the tumors have recurred after local
excision that was usually incomplete.
■ PVF has been considered either a hormonally induced
physiologic proliferation of indigenous tissues or a
hamartoma.
Differential diagnosis
■ Aggressive angiomyxoma. These tumors occur in a
postpubertal age group, are usually deeply seated, and
have a diffusely myxoid matrix, perivascular smooth
muscle, and desmin+ cells.
■ Angiomyofibroblastoma. These tumors are well
circumscribed and contain perivascular desmin+
epithelioid cells.
■ Cellular angiofibroma. These tumors, unlike PVFs, are
well circumscribed, cellular, and contain numerous
blood vessels with hyalinized walls.
■ Neurofibroma. These tumors, unlike PVFs, contain
S100+ cells with wavy nuclei and many small nerve
fibers.
■ Fibroepithelial polyp. These lesions, unlike PVFs, are
polypoid, do not entrap surrounding tissues, and
have a more heterogeneous morphology that may
include hypercellular areas, multinucleated cells,
and mitoses.
Fig. 1.59 Prepubertal fibroma. Hyalinized fibrous tissue. (Courtesy of
Dr. Christopher Fletcher)
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 27
LIPOBLASTOMA-LIKE TUMOR
■ These rare tumors, which present as a vulvar mass in
young women (13–46 years of age), have a median size
of 5.6 cm and are usually grossly myxoid, lobulated, and
well defined.
■ Variable proportions of mature adipocytes, bland uni-/
bivacuolated lipoblasts, and spindle cells lie within a
myxoid stroma with prominent branching vessels.
Nuclear atypia is minimal, mitoses are rare, and necrosis
is absent.
■ The typical lack of PLAG1 and HMGA2 differs from true
lipoblastoma, and the usual loss of nuclear Rb
expression suggests a possible role of 13q chromosomal
alterations and a relationship with spindle cell lipoma.
■ A few tumors have recurred locally but none has
metastasized.
LEIOMYOMA AND RHABDOMYOMA
■ See Chapter 2 and Chapter 3.
FIBROUS, ADIPOCYTIC, VASCULAR, AND
NEURAL TUMORS (Fig. 1.60)
■ Fibrous tumors include rare examples of fibrous
hamartoma, desmoid tumor, fibromatosis of soft-tissue
type, and solitary fibrous tumor (SFT). SFT is considered
separately below as the case series by Yang et al. shows
that it appears to be more common in the vulva than
elsewhere in the female genital tract.
■ Adipocytic tumors include lipomas and lipoma-variants,
including spindle-cell lipoma, pleomorphic lipoma,
adenolipoma, and lipoblastoma-like tumors (see
corresponding heading).
■ Vascular tumors include glomus tumor, capillary and
cavernous hemangioma, hemangioendothelioma,
Fig. 1.60 Angiokeratoma. Typical dilated vessels, some with thrombi,
are seen in the superficial dermis.
angiokeratoma, and lymphangioma (including
lymphangioma circumscriptum).
• In some cases, vulvar hemangiomas have been part
of the blue rubber bleb nevus syndrome or the
congenital dysplastic angiopathy (Klippel–
Trenaunay–Weber) syndrome.
• Vulvar lymphangioma circumscriptum (acquired
lymphangiectasia) is usually related to a prior vulvar
operation, lymphadenectomy, and/or radiotherapy;
less common associations have included Crohn’s
disease, vulvar cellulitis, and lower limb lymphedema.
Striking dermal lymphangiectasia is typically
associated with marked reactive epidermal
hyperplasia.
• One case of vulvar spindle cell hemangiomatosis
occurred in a woman with Maffucci’s syndrome.
■ Vulvar examples of solitary (sometimes giant)
neurofibroma, neurofibromatosis, schwannoma, and
paraganglioma have been reported. Vulvar involvement
is rarely the presenting manifestation of
neurofibromatosis.
SOLITARY FIBROUS TUMOR
■ The largest series of this entity involving the female
genital tract found that 14 of 25 occurred in the vulva.
The patients were all adults, and eight were in the
reproductive age group.
■ The tumors in the series noted above ranged from 1 to
13.5 cm, most being <5 cm. They were typically well
circumscribed with a firm, uniform yellow–tan cut
surface.
■ Microscopic features are similar to those seen in the
general soft tissue location – bland spindle cells with no
particular pattern associated with prominent branching
ectatic blood vessels and a hyalinized stroma.
■ Occasional tumors are hypercellular and uncommon
features include fat, myxoid stroma, giant cells, and
cytologic atypia.
■ In the largest series the mitotic rate was ≤1 per 10
high-power fields in half the cases, brisk activity (up to
15 per 10 high-power fields) being seen in the other
cases.
■ Stat 6 and cd34 immunohistochemical stains are
typically positive.
■ Despite worrisome histologic features that led to 6 of 14
tumors in the noted series to be considered
morphologically malignant, metastases were not
documented albeit follow-up information was overall
suboptimal.
■ The differential diagnosis includes aggressive
angiomyxoma which is typically more myxoid and lacks
the large stag-horn-like vessels of solitary fibrous tumor.
Angiomyofibroblastoma may be considered but it
typically has a cuff of epithelioid cells around blood
vessels of a smaller caliber in contrast to solitary fibrous
tumor. In these and other rare issues in differential
diagnosis, staining for stat 6 may be an important
diagnostic aid.
28 • Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva
GRANULAR CELL TUMOR (Figs. 1.61–1.64)
■ Five to fifteen percent of granular cell tumors arise in
the vulva. Especially when multifocal, they may be
associated with similar tumors in extravulvar sites.
■ The patients, who are usually of reproductive or
postmenopausal age, present with solitary or
occasionally multiple subcutaneous nodules typically in
the labium majus, less commonly the clitoris or
perineum. Most tumors are <4 cm in size.
■ Irregular nests and sheets of eosinophilic, granular cells
with bland nuclei and usually <2 mf/10 hpf are
intermingled with strands of collagen and occasional
chronic inflammatory cells. The tumors may have a
pushing or infiltrative border. The neoplastic cells
Fig. 1.61 Granular cell tumor.
Fig. 1.63 Granular cell tumor. The granular nature of the cytoplasm
is evident on high power.
typically stain with PAS and immunoreact for S100,
α-inhibin, and calretinin.
■ The overlying epidermis or squamous epithelium often
shows striking degrees of pseudoepitheliomatous
hyperplasia that can mimic SqCC, especially in a
superficial biopsy specimen in which the granular cells
are sparse or absent.
■ The tumors are almost always clinically benign,
although some tumors recur locally. In one study, local
recurrence was only associated with tumors that had an
infiltrative border.
■ Six malignant vulvar granular cell tumors have
occurred in women 17–56 years of age; four had
nodal and/or hematogenous spread. No microscopic
features reliably correlated with malignant
behavior.
Fig. 1.62 Granular cell tumor, H&E and S100. Typical granular cells
are shown and demonstrate entrapment of skin appendages (left).
Strong immunoreactivity for S100 is typical (right).
Fig. 1.64 Granular cell tumor with pseudoepitheliomatous
hyperplasia. The underlying neoplasm (best seen lower right) has
elicited striking pseudoepitheliomatous hyperplasia, which could be
misdiagnosed as carcinoma. (Courtesy of Dr. Julie Irving)
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 29

Abbreviations and Acronyms

Access Expertconsult.com for a complete
list of all references
AA aggressive angiomyxoma
AGN atypical genital nevus
aka also known as
AMF angiomyofibroblastoma
BCC basal cell carcinoma
CMV cytomegalovirus
dVIN differentiated vulvar intraepithelial neoplasia
ER estrogen receptor
FGT female genital tract
GVHD graft-versus-host disease
HIV human immunodeficiency virus
HPV human papilloma virus
HSV herpes simplex virus
ISqCC invasive squamous cell carcinoma
LP lichen planus
LS lichen sclerosus
LSIL low-grade intraepithelial lesion
MSGC multinucleated stromal giant cell
NOS not otherwise specified
PCR polymerase chain reaction
PLV provoked localized vulvodynia
PR progesterone receptor
PVF prepubertal vulvar fibroma
SFT solitary fibrous tumor
SK seborrheic keratosis
SqCC squamous cell carcinoma
SCH squamous cell hyperplasia
SFT solitary fibrous tumor
SMA smooth muscle actin
VIN vulvar intraepithelial neoplasia
vs versus
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 29.e1
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myofibroblastoma: Expanding the morphological and
immunohistochemical spectrum. A clinicopathologic study of 10
cases. Hum Pathol 2012;43:243–253.
Magro G, Righi A, Casorzo L, et al. Mammary and vaginal
myofibroblastomas are genetically related lesions: Fluorescence in
situ hybridization analysis shows deletion of 13q14 region. Hum
Pathol 2012;43:1887–1893.
Stewart CJR, Amanuel B, Brennan BA, et al. Superficial cervicovaginal
myofibroblastoma: A report of five cases. Pathology 2005;37:
144–148.
Prepubertal vulvar fibroma
Ajibona OO, Richards CJ, Davies Q. A distinctive vulval fibroma of
so-called prepubertal type in a postmenopausal patient. J Clin
Pathol 2007;60:437–438.
Iwasa Y, Fletcher CDM. Distinctive prepubertal vulval fibroma: a
hitherto unrecognized mesenchymal tumor of prepubertal girls.
Analysis of 11 cases. Am J Surg Pathol 2004;28:1601–1608.
Vargas DO, Kozakewich HPW, Boyd TK, et al. Childhood asymmetric
labium majus enlargement mimicking a neoplasm. Am J Surg
Pathol 2005;29:1007–1016.
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the vulva: Report of three cases of a distinctive mesenchymal
neoplasm of adipocytic differentiation. Histopathology 2002;40:
505–509.
Mirkovic J, Fletcher CDM. Lipoblastoma-like tumor of the vulva:
Further characterization in 8 new cases. Am J Surg Pathol
2015;39:1290–1295.
Fibrous, adipocytic, vascular, and neural tumors
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pregnancy. Arch Pathol Lab Med 1997;121:512–514.
Biedrzycki OJ, Singh N, Habeeb H, et al. Solitary fibrous tumor of the
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Gynecol Pathol 2007;26:259–264.
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Obstet Gynecol 1989;73:877–879.
 Non-Neoplastic Lesions and Benign and Locally Aggressive Tumors of the Vulva • 29.e7

Busand B, Stray-Pedersen S, Iversen OH, et al. Blue rubber bleb nevus Sonobe H, Ro JY, Ramos M, et al. Glomus tumor of the female external
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hemangiomatosis associated with enchondromatosis: A rare Tjaden BL, Buscema J, Haller JA Jr, et al. Vulvar congenital dysplastic
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 CHAPTER 2

Malignant Tumors of the Vulva

SQUAMOUS CELL Adenocarcinomas of Skin Rare Sarcomas, Including

CARCINOMA AND ITS Appendage Origin Carcinosarcomas
PRECURSORS Rare Miscellaneous
Adenocarcinomas
Vulvar Intraepithelial
Neoplasia YOLK SAC TUMOR AND
Invasive Squamous Cell OTHER GERM CELL TUMORS
Carcinoma, Usual Type BASAL CELL CARCINOMA
Verrucous Carcinoma
Sarcomatoid Squamous Cell HEMATOLYMPHOID TUMORS
Carcinoma
MERKEL CELL TUMOR
Other Rare Variants of
Squamous Cell Carcinoma
LANGERHANS’ CELL
MALIGNANT MELANOMA HISTIOCYTOSIS
PAGET’S DISEASE

SMOOTH MUSCLE TUMORS OTHER RARE NEOPLASMS

CARCINOMA OF Myoepithelioma
BARTHOLIN’S GLAND Carcinoid Tumor
OTHER SARCOMAS Primitive Neuroectodermal
Tumor
Rhabdomyosarcoma
OTHER ADENOCARCINOMAS Liposarcoma
Adenocarcinomas of Epithelioid Sarcoma and
SECONDARY TUMORS
Mammary Type Malignant Extrarenal
Rhabdoid Tumor
Another random document with
no related content on Scribd:
„Houdt den misdadiger!” riep Mr. Geis.

„Ja zeker!” sprak Baxter, „wij zullen hem vasthouden!

„In naam der Engelsche wet neem ik u in hechtenis, [27]Mr. Geis, u

noemende Stein. De misdadiger zijt gij en niet Raffles!”

Baxter gaf den detectives een wenk, om Geis te boeien. Maar nog
voordat zij een hand naar den bedrieger konden uitsteken, haalde
deze een revolver te voorschijn, zette die tegen zijn voorhoofd—een
schot knalde en de bankdirecteur viel dood neer.

Eenige seconden lang staarden allen elkaar verschrikt aan, daarop

sprak Baxter, die zich het eerst had hersteld:

„Laat het lijk gerechtelijk schouwen! Hij is dood en heeft zijn misdaad
geboet!”

Charly Brand had gebruik gemaakt van de algemeene ontsteltenis

door ongemerkt de kamer te verlaten. Niemand, lette op hem en een
uur later zat hij, zooals hij met Raffles had afgesproken, in diens
studeerkamer, waar hij zijn vriend den tragischen dood van den
bankdirecteur meedeelde.

Ellenlange berichten stonden over deze zaak in de avondbladen en

de „Times” schreef, dat het tijd werd om een standbeeld op te richten
voor John Raffles. Honderden kleine luiden, voor wie hij de
spaarpenningen had gestolen om ze uit de klauwen van een schurk
te redden, zegenden hem.

McIntosh zat alleen, vervuld van haat, in de villa van zijn

medeplichtige en dacht erover na, hoe hij weer in het bezit zou
kunnen komen van zijn schat, dien Raffles van het eiland had
meegenomen.
Uit de couranten vernam hij den dood van Mr. Geis en daar hij in het
bezit was van een testament, waarin Mr. Geis hem had benoemd tot
erfgenaam van diens geheele nalatenschap, kon hij zichzelf
beschouwen als eigenaar der villa.

Maar hij bezat geen cent aan baar geld. Hij was niet eens in staat om
zijn bedienden te eten te geven.

McIntosh verkocht echter eenige kostbare schilderijen, betaalde zijn

bedienden en ontsloeg hen.

Alleen den chauffeur hield hij in dienst.

Hij kende uit vroegere dagen een misdadigerskroeg, aan het Strand
gelegen, waarvan de eigenaar, een Ier, een oud schoolkameraad van
hem was.

Dezen ging hij opzoeken.

„Tom,” sprak hij tot den grooten, sterk gebouwden man, die achter
zijn toonbank stond en den meest vervalschten brandewijn uit geheel
Londen voor zijn klanten tapte, „Tom, je moet mij helpen.”

De eigenaar der kroeg keek bij het hooren dezer stem zijn bezoeker
scherp aan en antwoordde:

„Bij den heiligen St. Patrick! Patt Jimmy, ben jij het zelf?”

Patt Jimmy was in vroegere jaren de boevennaam van McIntosh

geweest.

„Zooals je ziet,” antwoordde deze.

„Voor den duivel, wie heeft je losgesneden, toen je aan de galg

hing?” vroeg Tom. „Hebben de vogels je door de lucht gedragen? Ik
heb zelf in de couranten gelezen, dat je opgehangen zoudt worden
en op den morgen, waarop het met je was afgeloopen, dronken wij
een groot glas brandewijn van mijn beste soort op je gezondheid.
Ben je uit den dood herrezen? Dat is bij St. Patrick, een heel
zeldzame gebeurtenis!”

„Niet zoo merkwaardig als jij wel meent,” sprak McIntosh lachend.

„De strik, waaraan ik hing, was goed, maar zij hadden de galg een
beetje al te vlug in elkaar geslagen. Toen men de plank onder mijn
voeten wegtrok, om mij naar de eeuwigheid te sturen, viel ik wel in
een kuil, maar met mij plofte de heele galg naar beneden. Je weet
dat mijn keel niet veel te wenschen overlaat.

„Men schonk mij toen genade, omdat volgens de Engelsche wet,

niemand tweemaal mag worden opgehangen. Ik werd naar Australië
gezonden om daar de straten en wegen netjes te houden.

„Een duivelsche lol, als men een ketting met een kogel mee moet
sleepen aan zijn been, terwijl de zon zóó op je kop brandt, dat je
hersens bijna smelten.”

„En hoe ben je weer uit die braadpan geraakt?” vroeg Tom, terwijl hij
zijn ouden vriend nog een glas brandewijn inschonk.

McIntosh dronk het gemeene goedje in een enkelen teug leeg en

sprak met een vies gezicht:

„Geef mij eerst wat beters te drinken. Aan de galg te hangen is nog
heerlijk, vergeleken bij dit bocht! Dat doet meer kwaad aan de keel
dan een strop!”

„Wees blij, dat je mijn brandewijn nog kunt drinken”, bromde Tom.
„Maar hier heb ik een extra goed merk, dat ik alleen op feestdagen
schenk. Ik zal maar denken, dat jouw bezoek een feestdag voor mij
is. Drink en vertel mij dan, hoe je uit dien smeltoven bent gekomen.”
Hij schonk een nieuw glas vol, dat McIntosh onderzoekend proefde:

„Dit is beter. Je hadt dadelijk aan een feestdag moeten denken. Nu,
luister dan:

„Ik vond toevallig op den weg, waar ik werkte, een vijl en daarmee
bevrijdde ik mij.

„Het was een ellendig, verroest instrument. Maar in den nood vreet
de duivel vliegen. Elken nacht vijlde ik onder mijn deken aan den
ketting. Een vervloekt [28]moeilijk werkje! Het duurde twee maanden,
eer ik den ijzeren band had doorgevijld.

„Toen was ik vrij! Ik sloeg een oppasser, die zoo gek was om mij den
weg te willen versperren met een enkelen slag neer, nam hem zijn
geweer af en vluchtte het bosch in.

„De bereden politie zat mij achterna. Verduiveld, Tom, voor een
tweeden keer zou ik het niet hebben volgehouden.

„Zonder water, zonder brood zwierf ik verscheiden weken in de

wildernis rond, totdat het mij gelukte, een ouwen kameraad als
mijneigenaar terug te vinden. Hij ontfermde zich over mij en verborg
mij voor de speurhonden.

„Met hem ben ik nu naar Engeland teruggekomen en omdat de man

niet naar mijn raad wilde luisteren, is het slecht met hem gegaan en
—Scotland Yard heeft hem gisteren als lijk meegenomen.”

„Toch niet—niet—” Tom aarzelde.

„Ja zeker”, hielp McIntosh hem, „dezelfde, dien jij bedoelt!”

„Is het mogelijk? Mr. Geis die zich Stein noemde! Vroeger bekend
onder den naam „Dikke Leg”.
„Jawel, dezelfde!—Verduiveld, Dikke Leg, die kassier aan een groote
Bank is geweest, je weet wel. Nou, de kerel had een flink
zondenregister, dat verzeker ik je!”

„Dat geloof ik,” sprak de herbergier.

„Toch is het jammer van den kerel,” vond McIntosh. „Hij had goede
plannen en als die vervloekte Raffles ons dezen keer geen streep
door de rekening had gehaald, was ik nu in het bezit van millioenen
en behoefde ik jou slechten brandewijn niet te drinken.”

„Je schijnt een erg voornaam heer te zijn geworden. Ik vraag je

immers niet om mijn borrels te drinken!”

„Dat klopt,” bromde McIntosh.

„Je hebt zeker wel een doel voor je komst?” informeerde Tom.

„Schenk mijn glas nog eens vol met die goeie soort, dan zullen wij
met elkaar spreken. Ik denk wel, dat je mij zult begrijpen en
meedoen. Maar hier kan ik het je niet vertellen. Je hebt zeker wel een
andere kamer?”

Tom schonk het glas nog eens vol en nam zijn bezoeker mee naar
een vertrek, achter de gelagkamer gelegen.

„Nou, wat heb je op je hart?” vroeg Tom, nadat beiden in de

rommelige kamer hadden plaats genomen.

McIntosh onderzocht eerst of niemand hun gesprek zou kunnen

hooren.

„Het is hier veilig,” sprak de waard, „maak je niet ongerust.”

McIntosh boog zich naar hem toe en fluisterde:

„Heb je lust, een rijke kerel te worden?”

„Ik zou niet weten, waarom niet,” antwoordde Tom, „Hongerlijden is

lang geen pretje.”

„All right,” ging McIntosh fluisterend voort, „ik weet een zaakje, dat
millioenen oplevert.”

„Dat laat zich hooren,” antwoordde Tom begeerig. „Een moord?”

„Als het noodig is, ja. Gemakkelijk is het niet,” vertelde de Ier, een
sigaar opstekend.

„Ik heb niet graag met moorden te doen. Het geeft te veel herrie.”

„Zoo was je vroeger niet,” hoonde McIntosh, „ik zal je een kindermeid
sturen!”

„Vertel, wat het is. Als het moet, sla ik altijd nog een kop in tweeën.
Je kent mij. Ik heb voor slager gestudeerd.”

Zij staken de hoofden bijeen en McIntosh begon:

„Je herinnert je wel, dat ik twaalf jaar geleden den ouden bankier
Burns— — —”

„Ja, dat weet ik, dat hoef je niet te herhalen. Daarom zou je worden
opgehangen. Het was een beroerde geschiedenis voor je.

„Als dit zaakje niet heel goed in mekaar is gezet, neem dan liever een
ander mee dan mij, want ik bedank voor dergelijke stropdassen.”

„Als er gemoord moet worden, neem ik dat voor mijn rekening”,

antwoordde McIntosh, „en ik hoop, dat het zal gaan zonder roode
soep te maken.”
„Mooi!” sprak Tom met een breeden grijns, „vertel verder kerel.”

„Ik heb toen,” vervolgde McIntosh, „anderhalf millioen van den ouden
bankier gestolen en had de papieren en het geld begraven op een
eilandje in de buurt van IJsland.”

„Een mooie plaats,” lachte Tom, „daar zoeken de fijnste speurhonden

van Scotland Yard de centen niet.”

„Neen, dat spreekt,” antwoordde McIntosh, de glazen opnieuw

vullende.

Nadat zij gedronken hadden, ging hij verder:

„Ik had nooit gedacht, dat het iemand zou gelukken, de duiten te
vinden, maar”—hij sloeg met de vuist op tafel, „de duivel hale dien
hond.”

„Wien?”

„Raffles! De grootste gauwdief van deze eeuw!

„Het is Raffles gelukt, den buit te vinden!” [29]

Nu sloeg ook Tom met de vuist op tafel, zoodat de glazen rinkelden

en hij riep uit:

„Vervloekt, Patt Jimmy, wat zeg je daar? Raffles, de groote

onbekende, heeft je een poets gebakken?”

„Jawel,” riep McIntosh met van woede vonkelende oogen, „door een
grenzenlooze domheid van mij is het hem gelukt.”

Tom riep lachend:

„Jongens, wat ben jullie dom! Jullie waagt je leven en steelt en laat
den boel door Raffles weghalen. Dat is een grap voor een
humoristisch album! Jij hangt aan de galg en hij staat er bij een
havanna te rooken, die hij voor het geld heeft gekocht, dat jou aan de
galg bracht. Kerel, dat is al te mal! Hoe was dat mogelijk?”

„Vraag er niet naar,” sprak McIntosh, „ik zeg je immers dat ik een
stommiteit heb uitgehaald en nu moet jij me helpen, alles terug te
halen.”

„Als het mogelijk is, graag,” sprak Tom. „Ik ben nieuwsgierig, hoe je
dat wilt aanleggen. Jij zoudt de eerste wezen, wien het gelukte om
Raffles een poets te bakken.”

„Ik denk wel, dat het zal lukken,” sprak McIntosh op geruststellenden
toon.

„Luister. Ik zal vannacht te weten zien te komen, hoe de woning van

Raffles is gebouwd.”

Tom keek verrast op:

„Weet je, waar de hond woont? Dat is vijfduizend pond sterling

waard, die als belooning worden uitbetaald!”

„Wij moeten meer hebben dan vijfduizend pond.”

„Dat ben ik volkomen met je eens, als het kan! Maar hoe is het
mogelijk, dat jij weet, waar hij woont? Geheel Scotland Yard weet het
niet!”

„Dat ben ik van mijn kameraad te weten gekomen en daarop is mijn

plan gebouwd!”
„Ik neem aan, dat alles wat je zegt, waarheid is. Hoe denk je de zaak
aan te pakken? Het zal zeker niet gemakkelijk zijn.”

„Dat hangt van jou af,” antwoordde McIntosh. „De hoofdzaak is, dat ik
een flinke hulp heb. Want alleen geloof ik niet, met Raffles klaar te
zullen komen.”

„Goed,” sprak Tom, „als je je plan hebt opgemaakt, kom dan bij mij. Ik
zal je helpen. Maar eerlijk deelen!”

„Dat spreekt van zelf,” gaf McIntosh ten antwoord, „of houdt je mij
soms voor een bedrieger?”

„Ik hoop niet, dat je er een bent; daar heb je mijn hand, het zal aan
mij niet liggen, om de zaak klaar te spelen.”

Den dag daarna zat Raffles met Charly in zijn bibliotheek en was
bezig, de courantenuitknipsels met berichten over zijn daden te
rangschikken, toen hij een geritsel hoorde aan de groote glazen deur,
die toegang gaf tot den tuin.

Hij maakte Charly Brand er niet opmerkzaam op, maar stond op en

sprak op onverschilligen toon:

„Kom, laat ons het werk tot morgen laten rusten en naar een
restaurant gaan.”

„Zooals je wilt,” antwoordde de secretaris bereidwillig en samen

verlieten zij het huis.

Eerst tegen middernacht kwamen zij terug.

Charly was verbaasd, toen hij zag, dat Raffles geen gebruik maakte
van den gewonen ingang, maar om de villa heenliep naar het andere
gedeelte van het huis. De maan wierp haar zwakke stralen naar
beneden, maar voor de scherpe oogen van Raffles was dit licht
voldoende.

Als een Indiaan liep hij telkens bukkend langs de paden, die hij elken
dag door den bediende zorgvuldig liet harken. Elke voetstap liet
daardoor zijn spoor achter. Spoedig had Raffles dan ook gevonden
wat hij zocht.

Hij wees met zijn hand naar de duidelijke sporen van groote
mannenlaarzen.

„Houdt je kalm,” fluisterde hij tot Charly, „wij hebben nachtelijk bezoek
in huis.”

Hij onderzocht de voetstappen verder en bleef eenige meters verder

opnieuw staan.

„Zij zijn met hun beiden,” sprak hij, „hier ontdek ik andere sporen.
Deze voeten zijn kleiner dan de andere.”

„Wie kan het zijn?” fluisterde Charly nieuwsgierig.

„Ik denk, een oude kennis,” antwoordde Raffles, „als ik mij niet heel
erg vergis, is het de medeplichtige van Mr. Geis.”

„Aha!” fluisterde Charly, „de kerel zal willen probeeren om zijn

schatten, die wij van het eiland meenamen, terug te krijgen.”

„Juist, juist en ik denk, dat ik hem leelijk voor den gek zal kunnen
houden. Hij is dom genoeg om mij een bezoek te komen brengen. Ga
jij nu naar de straatdeur en ga met veel lawaai het huis binnen. De
schurken moeten hooren, dat je thuis komt. Zij zullen natuurlijk
denken, dat ik het ben. Ga naar mijn studeerkamer, neem een
revolver voor geval van nood en wacht daar op mij.” [30]
Charly Brand ging heen, terwijl Raffles, de voetstappen volgend, naar
het huis sloop.

Hij ging langs denzelfden weg het huis binnen, dien de inbrekers
hadden genomen en dat geschiedde zoo onhoorbaar, alsof een
schaduw door het venster de bibliotheek binnen gleed.

Lord Lister had den kraag van zijn jas hoog opgeslagen en een
zakdoek voor het gelaat gebonden.

Alleen zijn oogen waren te zien, zij fonkelden als sterren.

Zoodra hij in de kamer was, bleef hij, alsof hij een inbreker was,
schuw staan en luisterde eenige oogenblikken.

Als een dief sloop hij daarna voorwaarts, totdat hij midden in het
vertrek stond.

Nu liet hij de dievenlantaarn, die hij in zijn zak droeg haar licht
verspreiden en trok zijn pistool te voorschijn.

Met scherpen blik ontdekte hij bij het licht der lantaarn op het tapijt,
dat den geheelen vloer bedekte, de sporen van de natte schoenen
der inbrekers.

Zij liepen dwars door het vertrek naar een fluweelen gordijn, dat een
erker afsloot en waarachter de mannen zich waarschijnlijk hadden
verborgen.

Aan een geringe beweging van het gordijn bemerkte Raffles dat hij
zich niet vergist had en dat de mannen hem in het oog hielden.

Hij doofde de lantaarn uit, en een tevreden lachje speelde om zijn

mond.
Zacht sloop hij naar het venster terug, opende het en liet een zacht
misdadigersfluitje, zooals men dat in Eastend gebruikt, hooren.

Daarop wachtte hij eenige seconden en riep duidelijk uit het raam,
alsof hij tot iemand in boeventaal sprak:

„Alles is koscher! (in orde) niemand te zien. Ik zal de boel uit het
raam gooien!”

Dat was wel zacht, maar toch zoo duidelijk gesproken, dat de
mannen achter het gordijn het moesten hooren.

Nu sloop Raffles weer door de kamer terug, waar hij voor een groote
eikenhouten kast staan bleef. Daarop stonden zware zilveren
kandelaars en vazen.

Raffles klom op een stoel, liet zijn lamp schijnen en nam de zilveren
voorwerpen van hun plaats. Nu zette hij de lantaarn op tafel en
onderzocht de zilverwerken der verschillende stukken.

„Goede mazzematten,” zei hij hardop en ging met zijn buit naar het
venster.

Weer floot hij en sprak:

„He Jim, pak aan, ik taxeer ze op tien pond. Zwaar goed!”

Hij wierp de zilveren kandelaars en kannen uit het raam en met een
luiden slag vielen deze op den grond.

Dadelijk doofde hij het licht weer uit en kroop, alsof hij tengevolge van
het rumoer vreesde overvallen te worden, onder de tafel.

Na eenige seconden kwam hij weer te voorschijn en naar het venster

snellend, riep hij:
„Nu zal ik de andere kamers doorzoeken en als alles koscher is,
komen jij en Jacq binnen.”

Nu sloop Raffles naar de studeerkamer, waar Charly Brand

intusschen was binnengekomen.

Charly Brand schrikte, toen Raffles, dien hij niet dadelijk herkende,
plotseling in de kamer stond en haastig tot hem sprak:

„Snel naar buiten! Bind een zakdoek voor je gezicht, evenals ik en

kom door hetzelfde raam naar binnen. Je moet voor inbreker spelen”.

Nu sloop Raffles naar de bibliotheek terug en overtuigde zich met

een enkelen blik, dat de hem onbekende inbrekers nog steeds achter
het gordijn verborgen waren.

Weer ging hij naar het venster en opende het. Toen hij naar buiten
keek, zag hij Charly Brand.

„He, Jim,” riep Raffles, „ik heb overal gezocht Er zijn twee heeren in
huis. Beiden slapen. Nu kunnen wij de kamers uitruimen. Jij, Jim,
moet hierkomen en Jacq blijft oppassen en de wacht houden.”

Bij deze woorden hielp hij Charly Brand door het venster naar binnen
klauteren en zamen slopen zij nu naar het aangrenzende vertrek.

Toen zij eenige kamers van de bibliotheek verwijderd waren, sprak

Raffles met een fijn lachje:

„Nu komt de grootste mop, die ik ooit in mijn leven heb beleefd. De
kerels staan achter het gordijn in de erker en zweeten bloed, omdat
er collega’s van hen bezig zijn. Nu zullen wij het tafelzilver uit de
eetkamer nemen en het ook uit het raam in den tuin gooien. Dan
keeren wij terug, jij neemt uit mijn kleedkamer een politiejas, je zet
een helm op en treedt op als beambte.”
Beiden namen een armvol zilveren schalen en borden en droegen
alles naar de bibliotheek.

„He, Jacq!” riep Raffles uit het raam, „Pas op, zeg!”

In het volgende oogenblik wierp hij de zilveren voorwerpen naar

buiten en Charly volgde zijn voorbeeld. [31]

„Duivelsch!” vloekte Charly! „niet zooveel lawaai, wij zijn hier niet
thuis!”

„Maak je niet ongerust”, antwoordde Raffles, „de heeren slapen vast.

Nu gaan wij de rest halen en dan er van door.”

Snel begaven zij zich naar de kleedkamer en nu verkleedde Raffles

zijn vriend in alle haast als politiebeambte. Daarop legde hij voor
zichzelf een tweede uniform en helm gereed, zonder ze aan te
trekken. Hij gaf Charly Brand een revolver en een paar boeien en
sprak tot hem, de eetkamer binnengaande:

„Nu ben jij een politieman en achtervolgt mij. Je blijft bij het venster
der bibliotheek staan, totdat ik als politiebeambte bij je terugkom.
Laat de kerels er niet uit. Houdt je flink, mijn jongen. Je moet bij het
raam der bibliotheek blijven staan tot ik je een teeken geef.”

Daarop nam hij het zilver, dat op het buffet stond, wierp het met groot
lawaai op den grond en beval op luiden toon, zoodat het door alle
kamers weerklonk:

„Sta stil! Handen in de hoogte!” terwijl hij zijn revolver tweemaal

afschoot.

Daarop fluisterde hij tot Charly Brand:

„Schreeuw, alsof je een ambtenaar van politie was en volg mij!”

Als vluchtende snelde Raffles nu door de kamers tot de bibliotheek,
op zijn weg stoelen en tafels omverwerpend.

Toen hij het raam der bibliotheek had bereikt, schreeuwde hij naar
buiten:

„Vlucht Jacq. De politie heeft ons overvallen. Zij hebben Jim

doodgeschoten!”

Bij die woorden sprong hij uit het raam en was verdwenen in de
duisternis.

In het volgende oogenblik snelde Charly Brand, verkleed als

politiebeambte, de bibliotheek binnen en riep een luid „Halt!” Hij liep
naar het raam en vloekte op woedenden toon:

„Vervloekt! De schurk is gevlucht, dat bezorgt mij een standje van

den inspecteur!”

Hij sloot het raam en om den tijd te dooden, totdat Raffles terug zou
komen, draaide hij het electrische licht in de kamer op en begon alles
door te zoeken.

„Aha!” riep hij uit, „zij hebben het zilver van de kast weggenomen.”

Daarop liep hij naar de deur en riep, alsof hij tot iemand sprak:

„Kapitein, de kerel is gevlucht!”

„Neen,” riep Raffles terug, die zich in dezen korten tijd had verkleed
als inspecteur van politie. „Wij hebben het geheele huis omsingeld,
niemand kan ontsnappen.”

Kort nadat hij deze woorden gesproken had, trad hij de bibliotheek
binnen en sprak:
„Wij zullen alles doorzoeken. Het moet een geheele bende zijn.
Revolvers gereed houden!”

Nauwelijks had hij deze woorden gesproken of van achter het

fluweelen gordijn kwamen McIntosh en Tom te voorschijn, een poging
doende om door het venster te vluchten.

„Halt!” riep Raffles, hun zijn revolver voorhoudend, „hier hebben wij
twee schurken van de bende.”

Door vrees voor de uniformen en de op hen gerichte revolvers gaven

de beide schurken zich zonder tegenstand over.

Raffles legde hun de boeien aan.

„Beste Scotland-Yard-armbanden,” schertste hij, „van uitstekend

Dublinsch staal gemaakt. En nu vooruit!”

Hij greep McIntosh bij den arm, terwijl Charly Brand Tom’s polsen
beetpakte.

Daarop brachten zij het tweetal de straat op.

Toen zij buiten waren, sprak Tom:

„Weet gij, inspecteur, dat gij een betere vangst daar in huis hadt
kunnen doen, dan ons mee te nemen?”

„Dat geloof ik niet,” antwoordde Raffles.

„Maar ik wel,” sprak Tom, „in dat huis woont Raffles, de meesterdief,
dien gij al zoo lang zoekt!”

„Je bent gek, kerel,” lachte Raffles, „in dat huis woont de ouder
professor Morton, dien ik heel goed ken. En nu je mond houden!”
Toen riep Tom, met een woedenden blik op McIntosh:

„Ik zei je dadelijk, dat je je wel zoudt vergissen. Nu breng je mij ter
wille van een ouden professor naar Scotland Yard.”

McIntosh knarste met de tanden.

Geis moest hem hebben voorgelogen, of Raffles had Geis iets op

den mouw gespeld.

Het spel was verloren.

Toen zij den naasten politiepost hadden bereikt, maakten zij halt.
Raffles gaf zijn gevangenen aan de beambten over:

„Ik heb een jacht op inbrekers gehouden voor Scotland Yard, neem
een berichtje van mij mee. Breng deze mannen aan inspecteur
Baxter. Weest voorzichtig, het zijn sterke kerels!”

Hij scheurde een blad papier uit zijn notitieboekje [32]en schreef een
briefje. Dat sloot hij in een couvert en gaf het aan een der beambten,
die het bij zich stak.

„Maak dadelijk gebruik van de wapens”, riep Raffles tot de zich

verwijderende mannen, „als gij merkt, dat de jongens willen vluchten!”

Een half uur later werden, tot groote verbazing van inspecteur Baxter,
de beide gevangenen bij hem binnengebracht.

Baxter opende het briefje van zijn collega en las:

„Inspecteur Baxter! Ik heb u moeten vertegenwoordigen. Ik zend u als

resultaat van mijn werk deze beide inbrekers. Gij zult in den een een lang
gezochten, ouden bekende terugvinden. Hij was de medeplichtige van
onzen vriend Mr. Geis.

Met collegialen groet!

 Raffles.”

„Wat?” lachte Marholm, „stuurt Raffles die twee?”

„Ja”, antwoordde Baxter, „Raffles!”

Toen McIntosh dit hoorde werd hij bijna krankzinnig van woede en
brulde hij als een bezetene.

Raffles echter zat in zijn gezellige studeerkamer en amuseerde zich

over zijn laatste werk, terwijl Charly Brand het zilver weer op zijn
plaats borg en met leedvermaak constateerde, dat het eenige deuken
had gekregen.

[Inhoud]

De volgende aflevering (No 26) bevat:

Inspecteur Baxter in het

Krankzinnigengesticht. [33]

[Inhoud]

Belooning: 1000 pond sterling.

 Wie heeft
Wie kent
hem
hem?
gezien?

Dat vraagt
men in Dat vraagt
Scotland heel Londen!
Yard!

Lord Lister genaamd John C. Raffles, de

geniaalste aller dieven

brengt alle gemoederen in beweging, is de schrik van woekeraars en

geldschieters; ontrooft hun door zijn listen hunne bezittingen,
waarmede hij belaagde onschuld beschermt en behoeftigen
ondersteunt.

Man van eer in alle opzichten

spant hij wet en gerecht menigen strik en heeft steeds de

voorvechters van edele levensbeschouwing op zijn hand, nl. allen,
die ervan overtuigd zijn, dat:
Ongestraft veel misstanden, door de wet beschermd,
blijven voortwoekeren.

Men leze, hoe alles in het werk wordt gesteld, Lord Lister, genaamd
John C. Raffles, den geniaalsten aller dieven, te vatten!

[Inhoud]

Vertaling:
WARRANT OF
ARREST. Bevel tot
aanhouding.

Be it known unto all men by these Wij verzoeken de aanhouding van

presents that we hereby charge den man, wiens beschrijving hier
and warrant the apprehension of volgt:
the man described as under:

DESCRIPTION: Beschrijving:

Name: Lord Edward Naam: Lord Edward

Lister, alias John Lister,
C. Raffles. genaamd John
Age: 32 to 35 years. C. Raffles.
Height: 5 feet nine Leeftijd: 32–35 jaar.
inches. Lengte: ongeveer 1,76
Weight: 176 pounds. meter.
Figure: Tall. Gewicht: 80 kilo.
C o m p l e x i o n : Dark. Gestalte: slank.
Hair: Black. G e l a a t s k l e u r : donker.
Beard: A slight Haar: zwart.
moustache. Baardgroei: kleine snor.
Eyes: Black. Oogen: zwart.
Language: English, French, Spreekt Engelsch,