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Benign lung tumors and tumor-like lesions

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5 BENIGN LUNG TUMORS AND

TUMOR-LIKE LESIONS

grace c. h. yang, m.d.

INTRODUCTION Radiographic features

Pulmonary hamartoma typically presents as an incidental
Of all the organs, lung is the most likely to have a false-
“coin lesion” on CT scan (Fig. 5.1) and with rounded
positive cytologic diagnosis, because irritated type 2 pneu-
abnormality with a popcorn pattern of calcification on
mocytes can become markedly atypical with enlarged
chest X-ray. It frequently occurs subpleurally. The nodule
hyperchromatic nuclei and prominent nucleoli, mimicking
bounces away from the advancing needle like a marble due
adenocarcinoma. This chapter deals with benign lung
to the cartilaginous component.
tumors and non-infectious tumor-like lesions. In most hos-
pitals, approximately 30% of the transthoracic fine needle
aspiration (FNA) biopsies are benign. Some benign lesions, Cytologic features
i.e., sarcoidosis, radiologically mimick malignancy, present-
Aspirates obtained from pulmonary hamartoma are char-
ing as lung masses with hilar adenopathy. Positive positron
acterized by fragments of metachromatic mesenchymal tis-
emission tomography (PET scan) in a metastatic work-up
sue with or without associated sheets of small bland
can be alarming clinically. One needs to remember that a
epithelium (Fig. 5.2). The metachromatic substances are
PET scan measures metabolic activity. Increased uptake can
fibromyxoid tissue or less frequently cartilage, which is
occur in metabolically active but benign lesions.
located deeper and harder to reach with the needle.
Cytopathologists are sometimes under pressure from clini-
Sometimes, bundles of spindly smooth muscle cells inter-
cians to overcall a lesion so the diagnosis matches clinical
spersed with fat are present (Fig. 5.3). Pulmonary hamar-
impression. One needs to remember that the truth lies in the
toma are sometimes underdiagnosed by FNA, since the lung
cells and substances that are sampled from the lesion.
nodule may bounce off the needle and only metachromatic
Although bronchial brushes and transbronchial FNA are
substance is sampled without associated epithelium. The
done by pulmonologists, the vast majority of the diagnostic
cytologist may be focusing on looking for epithelial cells
cases in this author’s experience were obtained by radiolog-
while ignoring the stromal fragments. However, if one
ists using a percutaneous transthoracic approach.
pays attention to the metachromatic mesenchymal sub-
stance on Diff-Quik stain, and it correlates with the radio-
logy, the diagnosis of pulmonary hamartoma is
PULMONARY HAMARTOMA
straightforward.

Clinical features
Pulmonary hamartomas account for about 75% of benign
lung tumors. Grossly, the tumor is a sharply delineated and
lobulated ovoid nodule, measuring up to 4 cm. It most
commonly occurs in adults, usually men. It sometimes
presents as an intrabronchial polypoid mass causing
obstruction.
Key features: pulmonary hamartoma
* Metachromatic mesenchymal tissue (fibromyxoid tissue,
less frequently cartilage)
* Sheets of small bland epithelium (present or absent)
* Smooth musle cells interspersed with fat (present or
absent)

Lung and Mediastinum Cytohistology, ed. Syed Z. Ali and Grace C. H. Yang. Published by Cambridge University Press. © Cambridge University Press 2012.

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BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS
Figure 5.1 CT-guided FNA biopsy of a coin lesion. A “coin lesion” on
imaging study correlates to a well-circumscribed border on gross pathology.
Figure 5.3 Hamartoma. Aspirate is composed of respiratory
epithelium, lobulated fibromyxoid stroma, and sometimes smooth
muscle and fat. Papanicolaou, 400×.
* Potential to undercall as non-diagnostic in the absence of
epithelium
* Correlation with radiology
Histologic features
Pulmonary hamartoma are characterized by hyaline
cartilage covered by mesenchymal stroma with clefts lined
by bronchial epithelium (Fig. 5.4), beneath which are fat and
smooth muscle sometimes. The periphery of cartilage may
contain myxomatous tissue. In 15% of the hamartomas,
epithelium-lined myxoid fibroadipose stroma form papil-
lary projections that resemble immature placental villi.
Ancillary techniques
Immunohistochemistry is not necessary to diagnose pulmo-
nary hamartoma.
Figure 5.2 Hamartoma. Aspirates contain fragments of metachromatic
mesenchymal tissue associated with sheets of epithelium with small
uniform nuclei. Diff-Quik, 100×.
SOLITARY FIBROUS TUMOR
Clinical features
Solitary fibrous tumor originates from submesothelial mes-
enchymal cells, which are characterized by CD34 expres-
sion. Solitary fibrous tumors occur at all ages but have a peak
in the sixth and seventh decades of life; they occur equally in
men and women. Solitary fibrous tumors are asymptomatic
when small and found incidentally. Symptoms of chest pain,
cough, and dyspnea occur in about half of patients. Larger
solitary fibrous tumors may be associated with effusion,
hypoglycemia, and pulmonary osteoarthropathy.
Radiographic features
In addition to its classic presentation as a pleura-based mass,
solitary fibrous tumor can occur in many other sites, includ-
ing the lung as an intraparenchymal mass.
Cytologic features
Aspirates obtained from solitary fibrous tumor show vary-
ing degrees of cellularity. The majority of this type of lesion
yield keloid-like collageneous fibrous tissue (Fig. 5.5).
Aspirate taken near the edge of the lesion may show sheets
of mesothelium intimately associated with collagen fibers
(Fig. 5.6). A minority of solitary fibrous tumor yield spindle
cell-rich aspirate (Fig. 5.7), which may be overcalled as
sarcoma due to hypercellularity. However, overt malignant
nuclear features are absent.
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LUNG AND MEDIASTINUM CYTOHISTOLOGY
Figure 5.4 Hamartoma. Histology showing respiratory epithelium
lined by fibromyxoid stroma over hyaline cartilage (arrow). H&E, 400×.
(A) (B) (C)
Figure 5.6 Solitary fibrous tumor. (A) Mesothelium entrapped by
collagen bands. Papanicolaou, 100×. (B) Higher magnification showing
intranuclear inclusions in some of the mesothelial cells. Papanicolaou,
400×. (C) Note the nuclear inclusions in the rows of mesothelial cells
entraped within collagen bands in the resected tumor. H&E, 100×.
Key features: solitary fibrous tumor
* Variable cellularity
* Fibrous tissue with keloid-like collagen in most lesions
* Spindle cell-rich aspirate in some lesions
* Mesothelium entrapped by fibrous tissue may have
nuclear inclusions
* Potential overcall in spindle cell-rich region as sarcoma
due to patchy CD34 expression
Histologic features
Solitary fibrous tumor is characterized by fibroflast-like cells
with variable cellularity ranging from collagenous, keloid-
82
Figure 5.5 Solitary fibrous tumor. Majority of the tumors show
keloid-like collagenous fibrous tissue. (A) Papanicolaou, 400×. (B) Diff.
Quik, 40×.
(A) (B)
Figure 5.7 Solitary fibrous tumor. A minority of tumors have spindle
cell-rich aspirate. (A) Diff-Quik, 40×. (B) Papanicolaou, 400×.
like stroma to areas with numerous spindle cells. The tumor
has hemangiopericytoma-like blood vessels (Fig. 5.8), myx-
oid change with bland spindle cells in myxoid, vascularized
stroma, and may entrap mesothelium at the periphery of the
tumor (see Fig. 5.6, right).
Ancillary techniques
CD34 immunohistochemistry is helpful to confirm the
diagnosis of solitary fibrous tumor. However, CD34
expression can be focal and patchy; therefore, in small
samples such as FNA or core biopsy, CD34 may be neg-
ative. Vimentin should be diffusely positive confirming the
mesenchymal nature and Ki67 proliferation index should
be low.
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(A) (B)
Figure 5.8 Solitary fibrous tumor. Resected tumor measured 22 cm,
and showed region with sparse cellularity (A), intermediate cellularity
(B), and high cellularity (C). The spindle cell-rich aspirate shown in
Fig. 7.6 correlated to the area with high cellularity. H&E, 100×.
SCLEROSING PNEUMOCYTOMA
Clinical features
Sclerosing pneumocytoma used to be termed sclerosing
“hemangioma,” which has been proven to be scientifically
inaccurate, because the neoplastic cells express pneumocyte
marker and are negative for any of the blood vessel markers.
The tumor cells have progesterone receptors and typically
occur in older women with a mean age of 46 years.
Sclerosing pneumocytoma is almost always benign,
although regional lymph node metastases have been
reported in 2–4% of cases. Both surface epithelial cells and
the underlying mesenchymal cells derive from a common
pneumocyte precursor cell through divergent differentiation
during tumorigenesis.
Radiographic features
Sclerosing pneumocytoma typically presents as an inciden-
tal finding of PET (+) “coin lesion” on chest imaging, usually
smaller than 3 cm. When the needle is withdrawn from the
nodule, a resistance can be felt by the aspirator due to the
sclerosing nature of the mesenchymal element.
Cytologic features
Aspirates obtained from sclerosing pneumocytoma are char-
acterized by anastomosing small-caliber sclerotic stromal
fragments studded with many mesenchymal cells
BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS
(C) (Figs. 5.9B,C and 5.11A,B), which are in turn wrapped by a
layer of surface epithelium. In Diff-Quik stained smears, the
branching stromal fragments are metachromatic. Cross sec-
tion of the metachromatic core appears like rosettes on the
smears (see Fig. 5.9A and 5.10B). Surface epithelium stripped
off from the sclerotic stromal fragments by the smearing
showed small sheets of epithelium, ranging from bland (see
Fig. 5.11) to marked atypical with prominent nucleoli and
intranuclear inclusions, mimicking bronchioloalveolar carci-
noma (see Figs. 5.9D and 5.10C). However, the arrangement
of tumor cells is entirely different and the radiologic features
are coin lesion rather than ground glass opacity. Frequently,
the tumor cells may be separated by the smearing, mimicking
carcinoid (Fig. 5.10A). Cell block is especially helpful to
confirm the diagnosis of sclerosing pneumocytoma.
Key features: sclerosing pneumocytoma
* Branching small-caliber sclerotic stromal fragments
studded with mesenchymal cells which in turn are cov-
ered by a layer of surface epithelium
* The surface epithelial cells range from bland to markedly
atypical, mimicking bronchioloalveolar carcinoma –
potential for overcall
* The underlying mesenchymal stromal cells may be sep-
arated by smearing, mimicking carcinoid
* Cell block is especially helpful in confirming sclerosing
pneumocytoma.
Histologic features
Sclerosing pneumocytoma is a well circumscribed, but non-
encapsulated tumor (see Fig. 5.11C,D), with papillary or
islands of polygonal mesenchymal cells with indistinct cell
borders studded in the sclerotic stroma. The surface of
papillae is covered by a layer of fat (see Fig. 5.10D) to
cuboidal (see Fig. 5.11D) epithelium. The spaces between
papillae are narrow and slit-like. Trapped red blood cells
from the procedure may be present, giving the wrong
impression of hemangioma (see Fig. 5.10D).
Ancillary techniques
Immunohistochemistry on cell block is very helpful in the
specific diagnosis of sclerosing pneumocytoma (Fig. 5.12).
Both surface epithelial cells and the underlying mesenchy-
mal stromal cells coexpress TTF-1 and Progesterone
Receptor, while only surface epithelial cells are type 2 pneu-
mocytes with a CK7+/CK20 immunoprofile.
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LUNG AND MEDIASTINUM CYTOHISTOLOGY

(A) (C)

(B) (D)

Figure 5.9 Sclerosing pneumocytoma. Aspirated from a 49-year-old Chinese woman with a 1.3 cm PET (+) coin lesion. (A) Cross-sectional view of
stromal fragment (arrow). Note a group of epithelial cells in left lower corner. Diff-Quik, 400×. (B) Anastomosing branching stromal fragment
associated with tumor cells. Papanicolaou, 100×. (C) Longitudinal view of stromal fragment studded by mesenchymal cells. Papanicolaou, 400×. (D)
Surface epithelial cells with marked atypical nuclei with hyperchromasia, prominent nucleoli, and nuclear inclusions. Papanicolaou, 1000×.

SQUAMOUS PAPILLOMA contain small nuclei (Fig. 5.13). In addition, large cohesive
fragments of squamous epithelium with benign nuclei are
Clinical features present (Fig. 5.14A).
Squamous papillomas of the lung are an uncommon feature
of recurrent papillomatosis of the respiratory tract, occur- Key features: squamous papilloma
ring in fewer than 1% of cases. It occurs in large bronchi,
often associated with tracheal or laryngeal lesions. * Benign squamous cells with thin and translucent keratin
Squamous papillomas is caused by human papilloma virus and small nuclei
infection, often associated with dysplasia, carcinoma in situ, * Cohesive fragments of squamous epithelium with small
or invasive squamous cell carcinoma. nuclei
* Potential to overcall as well-differentiated squamous cell
carcinoma
Radiographic features * History of laryngeal papillomatosis
No data available.

Cytologic features
Aspirates obtained from squamous papilloma are charac-
terized by numerous benign squamous cells. The squamous
cells have abundant flat, thin, and translucent keratin and
Histologic features
Pulmonary squamous papillomas are characterized by cavi-
tary papillomas lined by squamous epithelium with under-
lying nests of non-invasive squamous cells within intact
alveolar spaces (Fig. 5.14B).

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BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS

(A) (C)

(B) (D)

Figure 5.10 Sclerosing pneumocytoma. Aspirated from a 33-year-old Chinese woman with a PET (+) 1.6 cm coin lesion. (A) Plasmacytoid tumor
cells, artificially separated by smearing, mimicking another coin lesion, carcinoid. Diff-Quik, 400x. (B) Mesenchymal cells attaching to stromal core,
imparting rosette-like appearance. Papanicolaou, 400x. (C) Markedly atypical epithelial cell with intranuclear inclusions. Papanicolaou, 400x.
(D) Mesenchymal cells embedded in sclerosing stroma, coated by epithelial lining cells, creating slit-like spaces. Red blood cells are contaminants
from aspiration. Cell block. H&E, 400x.

Ancillary techniques Radiographic features

Immunohistochemistry is unnecessary.
GRANULAR CELL TUMORS
Clinical features
Granular cell tumors are uncommon, usually benign neo-
plasms of putative Schwannian origin, most frequently orig-
inating from tongue, skin, and breast. In a study of 20 cases,
Deaver et al reported 6% to 10% of granular cell tumors
occur in the lung. Of the pulmonary granular cell tumors,
47% were incidental findings and 53% had obstructive
symptoms such as pneumonia or atelectasis, 16% had
hemoptysis, and 5% had weight loss. The granular cell
tumors were solitary in 75% of the patients, and multiple
in 25% of the patients.
Radiologically, granular cell tumors are usually smaller than
5 cm, but mimic malignancy on sonogram and CT scan due
to infiltrative borders, and MRI due to enhancement.
However, a PET scan is negative for metabolic activity.
Granular cell tumor has a hard consistency to the needle.
Cytologic features
Aspirates obtained from granular cell tumors are character-
ized by hypercellularity and are composed of uniform cells
with eccentric, round-to-slightly oval nuclei and abundant,
finely granular cytoplasm. The cells are fragile, with stripped
nuclei in a background of finely granular material
(Fig. 5.15A). The granularity is more pronounced in
Papanicolaou stain (Fig. 5.15B) than Diff-Quik stain.
Occasional cells with nuclear pleomorphism and small but

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LUNG AND MEDIASTINUM CYTOHISTOLOGY

(A) (C)

(B) (D)

Figure 5.11 Sclerosing pneumocytoma. Aspirated from a 44-year-old caucasian woman with a 2 cm PET (+) coin lesion. (A) Anastomosing stromal
fragment. Diff-Quik, 100×. Inset: Sheet of surface epithelium with nuclei ~1.5× RBC. 400×. (B) Anastomosing stromal fragment. Papanicolaou, 100×.
Inset: Surface epithelium with bland nuclei. 400×. (C) Circumscribed, but non-encapsulated tumor. H&E, 40×.(D) Long branching sclerotic stromal
papillary fragments coated by cuboidal surface epithelium. H&E, 400×.

conspicuous nucleoli were identified. Rare intranuclear tumor cells have the ultrastructural features of
cytoplasmic inclusions can be found. Schwannian cells with intertwining long cytoplasmic pro-
cesses, except the cytoplasm is filled with numerous
phagolysosomes.
Key Features: Granular cell tumors
* Syncytium of large granular cells with small nuclei with
distinct nucleolus Ancillary techniques
* many stripped nuclei of tumor cells bursted by the S-100 immunoreactivity is essential in confirming the cyto-
smearing logic diagnosis of granular cell tumors.
* S-100 positivity
* Suspicious radiologic features
CLEAR CELL “SUGAR” TUMOR (PECOMA)
Histologic features
Clinical features
Granular cell tumors are characterized by syncytial tumor
cells with abundant eosinophilic cytoplasm and small Clear cell “sugar” tumor is part of a family of tumors derived
nuclei, infiltrating surrounding tissue (Fig. 5.16). The from perivascular epithelioid cells (PEComas), including

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BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS

(A) (C)

(B) (D)

Figure 5.12 Sclerosing pneumocytoma immunoprofile. (A) Sclerosing stromal fragments with slit-like spaces lined by epithelium. Cell block
H&E, 400. (B) Progesterone receptor expression found in both epithelial cells and mesenchymal cells. 400×. (C) TTF-1 immunostain is diffusely
positive in both epithelial cells and mesenchymal cells, 100×. (D) CK7 immunostain is limited to surface epithelial cells, 100×.

(A) (B) (A) (B)

Figure 5.13 Squamous papilloma. (A) Aspirate showing superficial

squamous cells and an inflammatory background. Papanicoloau 100×. Figure 5.14 Squamous papilloma. (A) Large cohesive fragments of
(B) The squamous cells have abundant flat, thin, and translucent keratin benign squamous epithelium seen in other regions of the same aspirate.
and contain small nuclei. Papanicoloau, 400×. Papanicoloau, 40×. (B) Resected tumor showed papillary proliferation of
squamous epithelium with concentric whorls of squames. H&E, 40×.

renal and hepatic angiomyolipoma, pulmonary lymphan- express myogenic and melanocytic markers, i.e., actin and
gioleiomyomatosis, clear cell myomelanocytic tumor of HMB45.
falciform ligament, and abdominopelvic sarcoma of peri- Clear cell “sugar” tumor can occur in any age group with
vascular epithelioid cells. The tumor cells of PEComas a slight female predominance. Rarely, this tumor is

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LUNG AND MEDIASTINUM CYTOHISTOLOGY
(A) (B)
Figure 5.15 Granular cell tumor. (A) Cohesive cells with abundant
granular cytoplasm and indistinct cell borders in a background of
stripped nuclei and granular cytoplasmic contents. Diff-Quik, 100×.
(B) Large cells with small ovoid nuclei with distinct nucleolus and
granular cytoplasm with indistinct cell borders. Many stripped nuclei
in background of cytoplasmic contents. Papanicolaou, 400×.
associated with tuberous sclerosis. These tumors are impor-
tant to diagnose pre-operatively, since simple wedge exci-
sion is usually curative.
Radiographic features
Clear cell “sugar” tumors are incidentally discovered as
solitary, small, sharply outlined PET (+) “coin lesions”
located within the peripheral lung.
Cytologic features
Aspirates obtained from clear cell “sugar” tumors are char-
acterized by cohesive clusters of clear tumor cells with trans-
gressing blood vessels (Fig. 5.17). The amount of clear
cytoplasm ranges from abundant (Fig. 5.18). to moderate
(see Fig. 5.17) to scanty (Fig. 5.19). In Diff-Quik stained
smears, clear (glycogen) vacuoles and naked nuclei released
by bursted tumor cells can be seen in the background (see
Fig. 5.17A). In most cases of clear cell “sugar” tumor, the
nuclei range from small round to oval nuclei to occasional
elongated nuclei with indistinct nucleoli (see Fig. 5.18B).
Rarely, a immunohistochemistry confirmed clear cell
“sugar” tumor shows bizzare nuclei with nuclear enlarge-
ment, anisonucleosis, hyperchromasia, prominent nucleoli,
and nuclear inclusions (Fig. 5.19D).
Key features: clear cell “sugar” tumors
* Cohesive groupings of epithelioid cells associated with
transgressing vessels
88
Figure 5.16 Granular cell tumor. Syncytial tumor cells with abundant
eosinophilic cytoplasm and small nuclei, infiltrating surrounding
tissue. H&E, 100×.
* Clear vacuoles within the cytoplasm and in the back-
ground of Diff-Quik stained smear
* Nuclei ranged from small uniform to atypical with
inclusions
* HMB-45 immunostain is positive, S-100 is focally
positive
* Potential to overcall as clear cell carcinoma
Histologic features
Clear cell “sugar” tumors are characterized by well-
circumscribed, but unencapsulated, sheets of polygonal
cells with clear to eosinophilic cytoplasm and numerous
PAS+ glycogen granules. The vascularity is prominent
with staghorn blood vessels. Frequently, the tumor cells
are large to medium sized polygonal cells with clear cyto-
plasm (see Fig. 5.18) and distinct cell borders. A wide spec-
trum of nuclear features can be seen, ranging from small,
uniform, round and oval, to elongated, to bizarre nuclei with
anisonucleosis, hyperchromasia, prominent nucleoli, and
frequent nuclear inclusions (see Fig. 5.19D). Extracellular
amorphous material with variable calcification may be
present.
Ancillary techniques
Immunoexpression is essential in the specific diagnosis of
clear cell “sugar” tumors. Clear cell “sugar” tumors are
HMB45 (+), S-100 (focal +), pancytokeratin (–), and
vimentin (+).
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BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS

(A) (C)

(B) (D)

Figure 5.17 Clear cell “sugar” tumor (PEComa) with small uniform nuclei. FNA of a coin lesion aspirated from a 68-year-old man. (A) On
Diff-Quik stained FNA smear, minute clear vacuoles (glycogen) released from cytoplasm of the tumor cells by the smearing. 200×. (B) Loosely
cohesive small tumor cells associated with transgressing blood vessels. Papanicolaou, 100×. (C) Cohesive fragments of clear cells with small nuclei.
H&E stain of cell block. H&E, 200×. (D) Positive HMB45 immunostain on cell block. 200×. (Courtesy of Dr. Kristen A. Atkins.)

(A) (B) MENINGIOMA

Figure 5.18 Clear cell “sugar” tumor (PEComa) moderate atypical
nuclei. (A) Wedge resection of the coin lesion from a 22-year-old female
showed well-circumscribed tumor with staghorn blood vessels. H&E,
40×. (B) High magnification showed sheets of sharply delineated large
cells with clear cytoplasm filled with glycogen. Inset: Moderate atypical
elongated nuclei. H&E, 400×.
Clinical features
Meningioma can occur outside the central nervous system,
usually involving the head and neck region or the para-
vertebral soft tissues. Pulmonary meningiomas may derive
from ectopic intrapulmonary arachnoidal cells, from the
pluripotential subpleural mesenchyme or from the pulmo-
nary meningothelial nodules. Pulmonary meningiomas
show morphological, immunohistochemical, and ultra-
structural features similar to their central nervous system
counterparts with fibroblastic, meningothelial, or transi-
tional subtypes. The largest series of pulmonary meningio-
mas was reported by Moran et al who studied seven
transitional type and three fibrous type pulmonary menin-
giomas in four women and six men with ages ranging
from 30 to 72 years (mean 51 years). Nine patients were

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LUNG AND MEDIASTINUM CYTOHISTOLOGY

(A) (C)

(B) (D)

Figure 5.19 Clear cell “sugar” tumor (PEComa) with marked atypical nuclei. (A) A 38-year-old man presented with a coin lesion. The aspiration
smear showed many bizarre nuclei with frequent intranuclear inclusions Papanicolaou, 400×. (B) Smear also shows rare cells with clear cytoplasm and
oval, mildly atypical nuclei. Papanicolaou, 400×. (C) Sharp delineated round tumor, correlated to “coin lesion” on chest imaging. Note the staghorn
blood vessels. Wedge resection. H&E, 40×. (D) Most tumor cells have marked atypical, round to oval, hyperchromatic nuclei with prominent
intranuclear inclusion. Some nuclei have prominent nucleoli. H&E, 400×.

asymptomatic except for one patient who had persistent
cough, which led to the discovery of the smallest tumor of
1.5 cm. The incidentally discovered tumors ranged in size
from 2 to 4 cm. There is no predilection to any particular
lobe or segments in the lung.
spindly (Fig. 5.20) or epithelioid cells (Fig. 5.21) in perivas-
cular arrangements. Occasional nuclear pseudoinclusions
(Fig. 5.21A) as well as binucleated cells with wispy cyto-
plasmic extensions were also noted. Psammoma bodies may
be seen.

Radiographic features Key features: pulmonary meningioma

Radiologically, pulmonary meningioma most commonly
presents as a PET (+) solitary well-circumscribed solid nod-
ule, incidentally found on chest imaging. However, it can
also present as multiple lung nodules, which need to be
distinguished from metastatic meningiomas from the cen-
tral nervous system. On CT scan, pulmonary meningioma
has soft tissue attenuation, lobulated margins, and no calci-
fications, but has increased uptake in PET scan.
Cytologic features
Aspirates obtained from pulmonary meningioma are hyper-
cellular with whorled nests of concentrically arranged bland
* Hypercellularity
* Whorled nests of concentrically arranged bland epithe-
lioid cells, often in perivascular arrangements in transi-
tional meningioma, which may be associated with
psammoma bodies
* Bundles of bland spindle cells
Histologic features
Meningiomas are characterized by whorled nests of con-
centrically arranged bland-appearing spindle cells accom-
panied by psammoma bodies. Both transitional and fibrous
types of meningiomas have been reported in the lung as

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BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS
(A) (B)
Figure 5.20 Meningioma. (A) Spindle cells with small oval nucleus
(1× RBC) in fibrous meningioma. Diff-Quik, 400×. (B) Fragment of
bland spindly cells with oval nucleus in fibrous meningioma.
Papanicolaou, 100×.
(A) (B)
Figure 5.22 Amyloidoma. (A) Metachromatic amorphous substance
Diff-Quik, 40×. (B) Amorphous substance associated with plasma cells.
Papanicolaou, 400×. Inset: Foreign body giant cell reaction with
innumerable nuclei may be present.
previously mentioned. The transitional type is associated
with psammoma bodies. Ultrastructurally, mengiomas
have abundant intermediate cytoplasmic filaments, com-
plex interdigitating cell processes, and desmosome-like cell
junctions.
Ancillary techniques
Meningiomas are immunoreactive for vimentin and EMA.
Approximately one-third of meningioma were reactive for
cytokeratin and one-third for S-100. Meningiomas have no
immunoreactivity for GFAP.
(A) (B)
Figure 5.21 Meningioma. (A) Syncytial whorls composed of
concentrically arranged meningial cells wrapped by spindly nuclei in
transitional meningioma. Arrow points to the nuclear inclusion. Diff-
Quik, 400×. (B)Cohesive fragments of epithelioid cells in transitional
meningioma. Papanicolaou, 100×.
AMYLOIDOMA
Clinical features
Amyloidoma is tumor-like nodular deposit of amyloid
fibrils. Pulmonary amyloidoma is a rare condition which is
usually found incidentally in asymptomatic, elderly individ-
uals. There is no association with generalized amyloidosis.
In some instances, amyloidomas may relate to pre-existing
chronic inflammatory conditions or may be associated with
autoimmune conditions such as Sjögren’s syndrome.
Radiographic features
Amyloidoma presents as multiple or much less commonly
solitary, PET (–), well-defined solid nodules with calcifica-
tions incidentally found during chest imaging.
Cytologic features
Aspirates obtained from amyloidoma are characterized by
abundant amorphous substance (Fig. 5.22) associated with
plasma cells and foreign body type giant histiocytes with
innumerable nuclei (Fig. 5.22, inset).
Key features: amyloidoma
* Abundant amorphous material
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* Giant histiocytes with innumerable nuclei (present or
absent)
* Plasma cells (present or absent)
Histologic features
Amyloidoma are characterized by sharply demarcated dense
amyloid deposits in the lung parenchyma and blood vessels
associated with a scant lymphoplasmacytic infiltrate that is
more prominent at the periphery of the nodule than in its
center. A foreign body type giant cell reaction is seen asso-
ciated with amyloid deposits.
Ancillary techniques
Congo Red stain is essential to confirm the diagnosis of
amyloidoma, which is Congo red positive with birefringence
under a polarized microscope.
SARCOIDOSIS
Clinical features
Sarcoidosis is a systemic granulomatous disease affecting the
lungs, lymph nodes, skin, eyes, liver, heart, and nervous,
musculoskeletal, renal and endocrine systems. The lungs
are involved in more than 90% of cases. The etiology is
unknown, but currently thought to be associated with an
abnormal immune response, triggered by unknown stimu-
lus. An association with Type IV hypersensitivity has been
Figure 5.23 Sarcoidosis. Hard granulomas in a clean background
without necrosis. Papanicolaou, 40×. Left inset: Close-up of the minute
granuloma indicated by the arrow, showing epithelioid histiocytes with
spindly nuclei. Right Inset: Diff-Quik, 100×.
92
described. Tests of delayed cutaneous hypersensitivity have
been used to measure progression. Sarcoidosis may be
asymptomatic or chronic. It commonly improves or clears
up spontaneously. More than two-thirds of people with lung
sarcoidosis are asymptomatic. About 50% have relapses and
about 10% develop serious disability. Certain tests, such as
the Kveim test where sarcoid material is injected into the
skin and elevated serum angiotensin converting enzyme, are
associated with sarcoidosis.
Radiographic features
Sarcoidosis presents as PET+ lung mass associated with hilar
lymphadenopathy mimicking malignancy radiologically.
Cytologic features
Aspirates obtained from sarcoidosis are characterized by
well-formed “hard” granulomas composed of epithelioid
histiocytes in a clean background (Fig. 5.23) and with neg-
ative AFB and fungal stains. The FNA diagnosis of non-
necrotizing granuloma is straightforward. It is up to the
clinician to confirm sarcoidosis by performing additional
tests and look for findings in other organs.
Key features: sarcoidosis
* Tightly packed compact and “hard” granulomas com-
posed of epithelioid histiocytes
* Clean background
(A) (B)
Figure 5.24 Sarcoidosis. Sarcoid type granulomas with Schaumann
bodies, asteroid bodies, and calcium oxalate crystals within giant cell
cytoplasm. Lymph node biopsy of the above case. (A) H&E, 40×. (B)
H&E, 400×.
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BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS

Histologic features (A) (B)

Classic sarcoid granulomas are “hard” granulomas replacing

the lymph node with Schaumann bodies, asteroid bodies,
and calcium oxalate crystals within giant cell cytoplasm
(Fig. 5.24).

Ancillary techniques
AFB stain and GMS stain are routinely requested to rule out
mycobacterial and fungal infection. However, host response
to infectious agents will show necrosis or neutrophilic infil-
tration, which are absent in sarcoidosis.
Figure 5.25 Wegener’s granulomatosis. (A) Rare reactive bronchial
epithelium (inset: 400×) seen among numerous inflammatory cells
(neutrophils, macrophages, and lymphocytes) and necrotic collagenous
WEGENER’S GRANULOMATOSIS fibrous tissue. Diff-Quik, 100x. (B) A poorly formed ganuloma
composed of a loose aggregate of epithelioid histiocytes below a large
Clinical features fragment of pathergic necrosis. Papanicolaou, 400×.

Wegener’s granulomatosis is a necrotizing granulomatous

inflammation accompanied by vasculitis, involving the
upper respiratory tract, lung, and kidneys. The disease
peaks at middle age with slight male predominance. Early
diagnosis and treatment can prevent renal failure and sub-
sequent death. Prompt institution of steroids and cyclo-
phosphamide result in remission in more than 90% of
patients. Although open lung biopsy may be necessary for
the definitive diagnosis of this disease, FNA can suggest this
entity and is confirmed by anti-neutrophil cytoplasmic anti-
body (ANCA) serology, sparing the patient open lung
biopsy.
disease as described below, and of the potential pitfalls of
overcalling irritated epithelial cells as adenocarcinoma.
Key features – Wegener’s granulomatosis
* Suppurative granulomas
* Loose aggregate of epithelioid histiocytes
* Collagen necrosis (pathergic necrosis)
* Irritated bronchial epithelial cells, potential to overcall as
adenocarcinoma
* Anti-neutrophil cytoplasmic antibodies (ANCA) in the
serum

Radiographic features
Wegener’s granulomatosis can present as a solitary lung
lesion or more commonly as multifocal lung lesions on
chest imaging studies.
Cytologic features
Aspirates obtained from Wegener’s granulomatosis are char-
acterized by distinctive collagen necrosis, poorly formed
granulomas composed of loose aggregates of elongated,
often palisading epithelioid histiocytes, and multinucleated
histiocytes (Fig. 5.25). Additionally, markedly atypical epithe-
lial cells can be seen. Cytopathologists need to be aware of the
variability of the FNA samples from different phases of this
Histologic features
Wegener’s granulomatosis is characterized by pathergic
necrosis, defined as irregular-shaped necrosis involving the
collagen and reticulum of vascular wall and the parenchyma
(Fig. 5.26). At the initial phase of the disease, palisading
granuloma and microabscesses predominate, followed by
widespread necrosis and then t the final phase of fibrosis.
Ancillary techniques
AFB and GMS stains are routinely requested to rule out
infectious etiology, since this entity is necrotizing granulom-
atous inflammation.

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LUNG AND MEDIASTINUM CYTOHISTOLOGY
Figure 5.26 Wegener’s granulomatosis. Pathergic necrosis on the right
showing distinctive eosinophilic, collagen necrosis. The poorly formed
granulomata on center left are composed of loose aggregates of
elongated, often palisading epithelioid histiocytes, and multinucleate
histiocytes. H&E, 40×.
(A) (B)
Figure 5.28 Inflammatory pseudotumor. (A) Cellular aspirate
composed of single cells scattered singly and in tissue fragments.
Papanicolaou, 100×. (B) The single cells are composed of mainly plasma
cells with eccentric nucleus, perinuclear hof, and blue cytoplasm. A few
lymphocytes and spindle cells are also present. Diff-Quik, 400×.
INFLAMMATORY PSEUDOTUMOR
Clinical features
Inflammatory pseudotumor often occurs in children and
young adults (age 30 or less) and is the most common
lung tumor in the 16 and younger age group. Progression
from organizing pneumonia to fibrous histiocytoma or to
plasma cell granuloma has been reported. Most patients are
aymptomatic, but approximately 25% may have cough,
dyspneas, fever, hemoptosis, or chest pain. Some patients
94
(A) (B)
Figure 5.27 Inflammatory pseudotumor. (A) Spindly myofibroblasts,
accompanied by plasma cells, lymphocytes, and histiocytes in a
collagenous or hyalinized stroma. Diff-Quik, 200×. (B) Spindly
myofibroblasts, accompanied by plasma cells, lymphocytes, and
histiocytes in a collagenous stroma. The spindle cells have bland nuclear
features. Papanicolaou, 400×.
may have hypergammaglobulinemia, leukocytosis, or ane-
mia that is reversible when the lesion is excised.
Radiographic features
Inflammatory pseudotumor typically presents as a solitary,
peripheral, sharply circumscribed mass with a tendency to
involve the lower lobes. In 3% of cases, the lesion is bilateral.
Involvement of adjacent parenchyma, mediastinum, and
hilar structures is a rare manifestation.
Cytologic features
Aspirates obtained from inflammatory pseudotumor
showed varying proportions of myofibroblasts, lympho-
cytes, plasma cells, eosinphils, and histiocytes. Some cases
contain many spindly myofibroblasts (Fig. 5.27), while other
cases may show sparse spindle cells in an aspirate with
predominance of plasma cells and lymphocytes (Fig. 5.28).
Some cases have myomatous stroma or dense fibrosis.
Inflammatory pseudotumor may also occur as a reaction
around a malignancy, resulting in a false-negative diagnosis.
Key features: inflammatory pseudotumor
* Varying proportion of spindle cells, plasma cells, lym-
phocytes, eosinophils, macrophages
* Children and young adults
* Solitary, peripheral, sharply circumscribed mass with
tendency to involve the lower lobes
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BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS

Histologic features (A) (B)

Inflammatory pseudotumors are characterized by a wide

variation of histologic appearances. The stroma ranges from
edematous to myxoid to fibrous to hyalinized. Myofibroblasts
are spindle-to-stellate-shaped and sometimes form whorls
and have thin, delicate cytoplasmic processes extending
from the main body of the cell. Histiocytes can be multi-
nucleated, and may contain lipid or hemosiderin. Alveolar
macrophages may be present.

Ancillary techniques
AFB and GMS stains are routinely ordered to rule out
Figure 5.29 Alveolar hemorrhagic syndrome. The aspirate showed a
infectious etiology. few clusters of irritated type 2 pneumocytes mimicking adenocarcinoma,
hemosiderin-laden macrophages in a bloody background (seen only in
Diff-Quik-stained smears) hemolysed and clarified in Papanicolaou-
stained smears. (A) 400×. (B) 1000×.
ALVEOLAR HEMORRHAGIC SYNDROME
(A) (B)
Clinical features
Diffuse alveolar hemorrhage is a clinical syndrome with
acute onset of leakage of red blood cells and fluid into the
alveolar spaces from the capillaries lining alveolar sacs. The
syndrome is associated with a broad spectrum of conditions
and includes leukemia patients undergoing chemotherapy,
radiation or bone marrow transplant; cocaine inhalation,
toxic exposures, drug reactions; pulmonary infections; auto-
immune diseases; bone marrow and organ transplantation;
mitral stenosis; coagulation disorders; pulmonary paucii-
mune capillaritis; and idiopathic pulmonary hemosiderosis.
Symptoms and signs range from dyspnea, cough to acute
respiratory failure. However, hemoptysis may be absent in Figure 5.30 Alveolar hemorrhagic syndrome. (A) Wedge biopsy
up to one-third of patients. showing hemorrhagic lung parenchyma. H&E, 40×. (B) Areas of irritated
type 2 pneumocytes. H&E, 400×.

Key features: alveolar hemorrhagic syndrome

Radiographic features
* Exceedingly bloody aspirate
Chest X ray and CT scan of alveolar hemorrhagic syndrome * Hemosiderin-laden macrophages
shows bilateral micronodular opacities. * Irritated type 2 pneumocytes, mimicking adenocarci-
noma may be found
* CT scan shows bilateral micronodular opacities
Cytologic features
Aspirates of lung nodules of alveolar hemorrhagic syndrome Histologic features
as expected are exceedingly bloody, and may contain
hemosiderin-laden macrophages and a few clusters of irri- Wedge resection of alveolar hemorrhagic syndrome is char-
tated type 2 pneumocytes, mimicking adenocarcinoma acterized by hemorrhagic lung parenchyma with irritated
(Fig. 5.29). type 2 pneumocytes (Fig. 5.30).

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LUNG AND MEDIASTINUM CYTOHISTOLOGY
Ancillary techniques
Immunohistochemistry is not useful in alveolar hemorrha-
gic syndrome.
RESERVE CELL HYPERPLASIA
Clinical features
Reserve cell hyperplasia typically results from chronic
irritation or injury of mucosal surface of bronchi or bron-
chioles by an offending agent. Examples include the toxic
effects associated with cigarette smoking or air pollution.
Inflammatory processes or infections such as sarcoidosis,
tuberculosis, chronic bronchitis, organizing pneumonia, or
bronchiectasis may also result in reserve cell hyperplasia and
squamous metaplasia. Reserve cell hyperplasia is increased
in smokers in proportion to smoking history.
Radiographic features
Reserve cell hyperplasia is not a mass lesion, thus undetect-
able by chest imaging.
Cytologic features
Reserve cell hyperplasia is seen in bronchial brushings and
washings with small hyperchromatic nuclei and invisible
cytoplasm (Fig. 5.31), similar to small cell carcinoma.
However, the reserve cells are more rigid lacking nuclear
streaking or nuclear molding. There is no pyknosis in the
background.
Figure 5.31 Reserve cell hyperplasia. Bronchial brushing. Basaloid cells
with high N/C ratio and rigid nuclei are present. Papanicolaou, 400×.
96
Key features: reserve cell hyperplasia
* Seen in bronchial brushing and washings
* Basaloid cells with high N/C ratio, mimicking small cell
carcinoma
* Rigid nuclei lacking nuclear streaking and molding
* Clean background without necrosis or pyknotic nuclei.
Histologic features
Reserve cell hyperplasia is characterized by the thickening of
basal cell layers.
Ancillary techniques
Immunohistochemistry can easily distinguish reserve cell
hyperplasia from small cell carcinoma. Unlike small cell
carcinoma, reserve cell hyperplasia is negative for neuro-
endocrine immunomarkers and low in Ki-67 proliferation
index.
CLINICAL VIGNETTES
Case 1
A 51-year-old woman presented with a large lung mass in
the right lower lobe (Fig. 5.32A). CT-guided FNA yielded
markedly atypical epithelial cells with enlarged nuclei and
prominent nucleoli (Fig. 5.32B,C). A diagnosis of adenocar-
cinoma was rendered. No lobectomy was performed because
of the patient’s poor health at the time. The lung mass had
completely disappeared at the 4 months follow-up CT scan.
Review of the FNA smears showed the atypical epithelium
to be sparse in quantity and occurred in flat sheets, and there
were numerous alveolar macrophages and debris in the
background of the smears (Fig. 5.32D). The marked atypical
epithelium cells in retrospect were type 2 pneumocyte
hyperplasia in resolving pneumonia. This illustrates the
importance of cellularity and biased mind set seeing a
large lung mass on CT scan.
Case 2
An 81-year-old woman, status post chemotherapy for acute
myeloid leukemia, developed mass-like consolidation in the
right lower lobe measuring 5 × 3.3 cm and with a radiodensity
of 23 Hounsfield Units. A CT-guided FNA was performed
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(A) (C)

(B) (D)

Figure 5.32 Case 1. A 52-year-old woman presented with a large lung mass. (A) CT-guided FNA. (B) Irritated type 2 pneumocytes with nuclei 6× RBC.
Diff-Quik, 400×. (C) Irritated type 2 pneumocytes with prominent nucleoli in flat sheets, Papanicolaou, 400×. (D) Scattered macrophages and
lymphocytes. Diff-Quik, 100×.

(A) (C)

(B) (D)

Figure 5.33 Case 2. An 81-year-old woman developed mass-like consolidation in right lower lobe, following chemotherapy for acute myeloid
leukemia. (A) CT-guided FNA using 22 gauge needle. (B) Cytologic smears showing network of alveoli. Diff-Quik, left 20×, right, 100×. (C) Cell block
showed diffusely plugged alveolar spaces, H&E, 40×. (D) Plugs of fibroblastic connective tissue fulfiled the histologic criteria for bronchiolitis obliterans
with organizing pneumonia (BOOP). H&E, 100×.
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LUNG AND MEDIASTINUM CYTOHISTOLOGY
(Fig. 5.33A). The smears showed fragments of alveolar net-
work without pathologic change during on-site evaluation
(Fig. 5.33B). Additional pass was requested and placed in
CytoRich Red solution, which dissolved aspirated blood.
After centrifugation, the sediment was colored with request
of “no trim” by histology. Cell block study (Fig. 5.33C,D)
showed alveolar spaces plugged with fibroblastic connec-
tive tissue, diagnostic for bronchiolitis obliterans with
organizing pneumonia (BOOP). This case illustrates the
importance of cell block preparation for optimal patient
care. BOOP is typically diagnosed by open lung biopsy. A
good cell block study correlated with the clinical and radio-
logic data can sometimes avoid open lung biopsy.
FURTHER READING
Pulmonary hamartoma
DeMay RM. The art and science of cytopathology. Chicago: ASCP Press;
1996.
Tao, L-C. Guide to clinical aspiration biopsy: lung, pleura, mediastinum.
New York: Igaku-Shoin; 1988.
Xu R, Murray M, Jagirdar J, et al. Placental transmogrification of the lung
is a histologic pattern frequently associated with pulmonary
fibrochondromatous hamartoma. Arch Pathol Lab Med 2002; 126:
562–566.
Solitary fibrous tumor
Ali, SZ, Hoon, V, Hoda S, et. al. (1997). Solitary fibrous tumor: A
cytologic-histologic study with clinical, radiologic, and
immunohistochemical correlations. Cancer 81, 116–21.
Baliga, M, Flowers, R, Heard, K, et al. (2007). Solitary fibrous tumor of
the lung: A case report with a study of the aspiration biopsy,
histopathology, immunohistochemistry, and autopsy findings.
Diagn. Cytopathol. 35, 239–44.
de Saint Aubain Somerhausen, N, Rubin, BP, Fletcher, CD. (1999).
Myxoid solitary fibrous tumor: a study of seven cases with
emphasis on differential diagnosis. Mod. Pathol. 12, 463–71.
Sclerosing pneumocytoma
Devouassoux-Shisheboran, M, Hayashi, T, Linnoila, RI, et al. (2000). A
clinicopathologic study of 100 cases of pulmonary sclerosing
hemangioma with immunohistochemical studies: TTF-1 is
expressed in both round and surface cells, suggesting an origin from
primitive respiratory epithelium. Am. J. Surg. Pathol. 24, 906–16.
Einsfelder, BM & Müller, KM (2005) [“Pneumocytoma” or “sclerosing
hemangioma”: Histogenetic aspects of a rare tumor of the lung.]
Pathologe. 26, 367–77.
Kaw, YT & Nayak, RN (1993) Fine needle aspiration biopsy cytology of
sclerosing hemangioma of the lung: A case report. Acta Cytol. 37:
933–7.
98
Miyagawa-Hayashino, A, Tazelaar, HD, Langel, DJ, et al. (2003).
Pulmonary sclerosing hemangioma with lymph node metastases:
Report of four cases. Arch. Pathol. Lab. Med. 127, 321–5.
Ng, WK, Fu, KH, Wang, E, et al. (2001). Sclerosing hemangioma of lung:
A close cytologic mimicker of pulmonary adenocarcinoma. Diagn.
Cytopathol. 25, 316–20.
Wojcik, EM, Sneige, N, Lawrence, DD, et al. (1993) Fine needle
aspiration cytology of sclerosing hemangioma of the lung: A case
report with immunohistochemistry. Diagn. Cytopathol. 9, 304–9.
Yoo, SH, Jung, KC, Kim, JH, et al. (2005) Expression patterns of markers for
type 2 pneumocytes in pulmonary sclerosing hemangiomas and fetal
lung tissues. Arch. Pathol. Lab. Med. 129, 915–9.
Squamous papilloma
Cook., JR, Hill, DA, Humphrey, PA, et al. (2000). Squamous cell
carcinoma arising in recurrent respiratory papillomatosis with
pulmonary involvement: Emerging common pattern of clinical
features and human papilloma virus serotype association. Mod.
Pathol. 13, 914–8.
Katial, RK, Ranlett, R, Whitlock, WL (1994). Human papilloma virus
associated with solitary squamous papilloma complicated by
bronchiectasis and bronchial stenosis. Chest 106, 1887–9.
Granular cell tumor
Deavers, M, Guinee, D, Koss, MN, et al. (1995). Granular cell tumors of
the lung: Clinicopathologic study of 20 cases. Am J Surg Pathol 19,
627–35.
Hoess, C, Freitag, K, Kolben, M, et al. (1998). FDG PET evaluation of
granular cell tumor of the breast. J Nucl Med 39, 1398–401.
Liu, K, Madden, JF, Olatidoye, BA, et al. (1999). Features of benign
granular cell tumor on fine needle aspiration. Acta Cytol 43,
552–7.
Seo, IS, Azzarelli, B, Warner, TF, et al. (1984). Multiple visceral
and cutaneous granular cell tumors: Ultrastructural and
immunocytochemical evidence of Schwann cell origin. Cancer 53,
2104–10.
Clear cell “sugar” tumor (PEComa)
Bonetti, F, Pea, M, Martignoni, G, et al. (1994). Clear cell “sugar” tumor
of the lung is a lesion strictly related to angiomyolipoma: The
concept of a family of lesions characterized by the presence of the
perivascular epithelioid cells (PEC). Pathology 26, 230–6.
Edelweiss, M, Gupta, N, Resetkova, E (2007). Pre-operative diagnosis of
clear cell “sugar” tumor of the lung by computed tomography-
guided fine-needle biopsy and core-needle biopsy. Ann. Diagn.
Pathol. 11, 421–6.
Gaffey, MJ, Mills, SE, Askin, FB, et al. (1990). Clear cell tumor of the lung:
A clinicopathologic, immunohistochemical, and ultrastructural
study of eight cases. Am. J. Surg. Pathol. 14, 248–59.
Nguyen, GK (1989). Aspiration biopsy cytology of benign clear cell
“sugar” tumor of the lung. Acta Cytol. 33, 511–5.
Policarpio-Nicolas, ML, Covell, J, Atkins K (2008). Fine needle
aspiration cytology of clear cell “sugar” tumor (PEComa) of the
lung: Report of a case. Diagn. Cytopathol. 36, 89–93.
C:/ITOOLS/WMS/CUP-NEW/2780976/WORKINGFOLDER/ALIY/9780521516587C05.3D 99 [80–99] 16.11.2011 3:15PM
BENIGN LUNG TUMORS AND TUMOR-LIKE LESIONS
Meningioma
Baisden, BL, Hamper, UM, Ali, SZ (1999). Metastatic meningioma in
fine-needle aspiration of the lung: Cytomorphologic finding. Diagn.
Cytopathol. 20, 291–4.
Falleni, M, Roz, E, Dessy, E, et al. (2001). Primary intrathoracic
meningioma: Histopathological, immunohistochemical and
ultrastructural study of two cases. Virch. Arch. 439, 196–200.
Gaffey, JJ, Mills, SE, Askin, FB (1988). Minute pulmonary
meningothelial-like nodules. A clinicopathologic study of so-called
minute pulmonary chemodectoma. Am. J. Surg. Pathol. 12, 167–75.
Gomez-Aracil, V, Mayayo, E, Alvira, R, et al. (2002). Fine needle
aspiration cytology of primary pulmonary meningioma associated
with minute meningothelial-like nodules: report of a case with
histologic, immunohistochemical and ultrastructural studies. Acta
Cytol. 46, 899–903.
Meirelles, P, Souza, G, Ravizzini, G, et al. (2006). Primary pulmonary
meningioma manifesting as a solitary pulmonary nodule with a
false-positive PET scan. J. Thorac. Imaging 21, 225–7.
Moran, CA, Hochholzer, L, Rush, W, et al. (1996). Primary
intrapulmonary meningiomas: A clinicopathologic and
immunohistochemical study of ten cases. Cancer 78, 2328–33.
Radley, MG, di Sant Agnese, PA, Eskin, TA, Wilbur, DC (1989).
Epithelial differentiation in meningiomas. An immunohistochemi-
cal, histochemical, and ultrastructural study – with review of the
literature. Am J Clin Pathol. 92, 266–72.
Ueno, M, Fujiyama, J, Yamazaki, I, et al. (1998). Cytology of primary
pulmonary meningioma: Report of the first multiple case. Acta
Cytol. 42, 1424–30.
Amyloidoma
Hui, AN, Koss, MN, Hochholzer, L, et al. (1986). Amyloidosis presenting
in the lower respiratory tract: Clinicopathologic, radiologic,
immunohistochemical, and histochemical studies on 48 cases.
Arch. Pathol. Lab. Med. 110, 212–8.
Möllers, MJ, van Schaik, JP, van der Putte, SC (1992). Pulmonary
amyloidoma; Histologic proof yielded by transthoracic coaxial fine
needle biopsy. Chest 102, 1597–8.
Podbielski, FJ, Nelson, DG, Pearsall, GF, et al (1997). Nodular
pulmonary amyloidosis. J. Thorac. Cardiovasc. Surg. 114: 289–91.
Sarcoidosis
Hendrickx, BW, van Herpen, CM, Bonenkamp, JJ, et al. (2005). Positive
positron emission tomography scan in sarcoidosis and two
challenging cases of metastatic cancer. J. Clin. Oncol. 23, 8906–7.
Morell, F, Levy, G, Orriols, R, et al. (2002). Delayed cutaneous
hypersensitivity tests and lymphopenia as activity markers in
sarcoidosis. Chest 121, 1239–44.
Kumar, V Robbins and Cotran pathologic basis of disease, 7th ed.
Philadelphia: Elsevier/Saunders; 2005.
Wegener’s granulomatosis
Katzenstein, AL & Locke, WK (1995). Solitary lung lesions in Wegener’s
granulomatosis: Pathologic findings and clinical significance in 25
cases. Am. J. Surg. Pathol. 19, 545–52.
View publication stats
Mark, EJ, Matsubara, O, Tan-Liu, NS, et al. (1988). The pulmonary
biopsy in the early diagnosis of Wegener’s (pathergic)
granulomatosis: A study based on 35 open lung biopsies. Hum.
Pathol. 19, 1065–71.
Pitman, MB, Szyfelbein, WM, Niles, J, et al. (1992). Clinical utility of fine
needle aspiration biopsy in the diagnosis of Wegener’s
granulomatosis. A report of two cases. Acta Cytol. 36, 222–9.
Uppal, S, Saravanappa, N, Davis, JP, et al. (2001). Pulmonary Wegener’s
granulomatosis misdiagnosed as malignancy. Brit. Med. J. 322, 89–
90.
Inflammatory pseudotumor
Bahador, M & Liebow, AA (1973). Plasma cell granulomas of the lung.
Cancer 31, 191–208.
Bakhos, R, Wojcik, EM, Olson, MC (1998). Transthoracic fine-needle
aspiration cytology of inflammatory pseudotumor, fibrohistiocytic
type: A case report with immunohistochemical studies. Diagn.
Cytopathol. 19, 216–20.
Berardi, RS, Lee, SS, Chen, HP, et al. (1983) Inflammatory pseudotumor
of the lung. Surg. Gynecol. Obstet. 156, 89–96.
Machicao, CN, Sorensen, K, Abdul-Karim, FW, et al. (1989).
Transthoracic needle aspiration biopsy in inflammatory
pseudotumors of the lung. Diagn. Cytopathol. 5, 400–3.
Matsubara, O, Tan-Liu, NS, Kenney, RM, et al. (1988). Inflammatory
pseudotumors of the lungs: Progression from organizing
pneumonia to fibrous histiocytoma or to plasma cell granuloma in
32 cases. Hum. Pathol. 19, 807–14.
Thunnissen, FB, Arends, JW, Buchholtz, RT et al. (1989). Fine needle
aspiration cytology of inflammatory pseudotumor of the lung (plasma
cell granuloma): Report of four cases. Acta Cytol. 33, 917–21.
Alveolar hemorrhagic syndrome
Gallouj, K, Brichet, A, Lamblin, C, et al. (1999). Pulmonary
hemorrhagic syndrome after inhalation of cocaine. Rev Mal
Respir 16, 560–2.
Lynch, JP (1998). Alveolar hemorrhage syndromes. In: Fishman’s
pulmonary diseases and disorders. 3rd ed. (Ed. AP Fishman)
McGraw-Hill, New York.
Robbins, RA, Linder, J, Stahl, MG, et al. (1989). Diffuse alveolar
hemorrhage in autologous bone marrow transplant recipients. Am.
J. Med. 87, 511–8.
Specks, U (2001). Diffuse alveolar hemorrhage syndromes. Curr. Opin.
Rheumatol. 13, 12–7.
Weisdorf, DJ (2003). Diffuse alveolar hemorrhage: an evolving problem?
Leukemia 17, 1049–50.
Reserve cell hyperplasia
Auerbach, O, Hammond, C, Garfinkel, L (1979). Changes in bronchial
epithelium in cigarette smoking: 1955–1960 vs 1970–1977. N. Engl.
J. Med. 300, 381–6.
Grefte, JM, Salet-van de Pol MR, Gemmink, JH, et al. (2004).
Quantitation of Ki-67 expression in the differential diagnosis of
reserve cell hyperplasia vs. small cell lung carcinoma. Acta Cytol.
48, 608–12.
Laucirica, R & Ostrowski, ML (2007). Cytology of nonneoplastic
occupational and environmental diseases of the lung and pleura.
Archiv. Pathol. Lab. Med. 131, 1700–8.
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