Middle and Posterior Mediastinum: Grace C H Yang

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Middle and posterior mediastinum
Chapter · May 2012

DOI: 10.1017/CBO9781139023351.012
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12 MIDDLE AND POSTERIOR MEDIASTINUM
hong q. peng, m.d. and grace c. h. yang, m.d.
INTRODUCTION Radiologic studies for mediastinal mass lesions

Imaging studies used in the evaluation of mediastinal
Anatomy
masses include chest X-ray, computed tomograms (CT
As the widest part of the interpleural space, the middle scan), positron emission tomography (PET) scan, mag-
mediastinum contains the heart, the ascending aorta, the netic resonance imaging (MRI), and radionuclide scan-
superior vena cava, the bifurcation of the trachea into two ning imaging. Chest X-ray is often the first study to detect
bronchi, pulmonary artery and veins, phrenic nerve and a mediastinal mass. Lateral chest X-ray is particularly
lymph nodes. An irregular triangular space running parallel helpful for determining the compartment of the media-
with the vertebral column, the posterior mediastinum, con- stinum involved. CT scan can determine the size, shape
tains esophagus, thoracic duct, lymph nodes, descending (irregular vs. circumscribed), tissue density (cystic vs.
aorta, veins, spinal nerves and ganglions, sympathetic solid), and the precise location of the mediastinal mass
trunk, and associated ganglia and paraganglia. The boun- and its relationship to adjacent structures. It can also
dary for the posterior mediastinum anteriorly is the pericar- differentiate a mass originating in the mediastinum from
dium, posteriorly is the paravertebral sulci from the lower a mass encroaching on the mediastinum from neigh-
border of the T4 to T12, laterally is the mediastinal pleura, boring structures. PET scan measures the fluoro-
inferiorly is the diaphragm, and superiorly is the transverse deoxyglucose (FDG) uptake which correlates with meta-
thoracic plane (Fig. 12.1). bolic activity of the lesion. In addition to malignant
lesions, PET avid lesions also include benign neoplastic
Clinical features and metabolically active non-neoplastic lesions such as
sarcoidosis. PET/CT scan superimposes CT image over
Diverse mass lesions can occur in middle and posterior PET image so that the precise location, size, and shape, as
mediastinum. The majority of these lesions present as well as the metabolic activity of the mass can be deter-
an asymptomatic mass on chest X-ray. When symptoms mined. MRI provides superior vascular imaging and can
occur, they are usually related to impingement on local delineate the relationship of the mediastinal mass to
structures, resulting in chest pain, dyspnea, dysphagia, nearby vascular structures. MRI can also detect the exten-
cough, superior vena cava syndrome, or neurologic deficits. sion of neurogenic tumors into the spinal canal or tumors
Middle mediastinum is the primary site for pericardial cysts, closely associated with the heart. Radionuclide scanning
bronchogenic cysts, and lymphomas. Posterior mediasti- imaging localizes neuroendocrine tumors. It shows high
num is the site for neurogenic tumors. Soft tissue tumors sensitivity and specificity in detecting neuroblastomas,
and metastatic tumors occur in both middle and posterior pheochromocytomas, and paragangliomas. Many radio-
mediastinum. Children tend to get lymphomas, neuroblas- labeled ligands targeting neuroendocrine biomarkers have
toma, ganglioneuroblastoma, and sarcomas, whereas in been developed for tumor localization and therapy pur-
adults, the most common tumors are carcinomas from the poses. 123I-MIBG is the agent of choice for diagnostic
lung and esophagus followed by neurogenic tumors and imaging.
lastly cysts and soft tissue tumors.
Lung and Mediastinum Cytohistology, ed. Syed Z. Ali and Grace C. H. Yang. Published by Cambridge University Press. © Cambridge University Press 2012.
227
LUNG AND MEDIASTINUM CYTOHISTOLOGY
surgery, cases of acute mediastinitis usually arose from

either perforation of the esophagus or from contiguous
spread of odontogenic or retropharyngeal infections.
However, in modern practice, most cases of acute mediasti-
nitis result from complications of cardiovascular or endo-
scopic surgical procedures. Treatment usually involves
aggressive intravenous antibiotic therapy and hydration. If
abscesses have formed, surgically drainage is indicated.
Radiographic features
Posterior
mediastinum CT scan is more sensitive than chest X-ray for detecting the
Anterior
mediastinum presence and extent of mediastinal fluid collections and
the presence of extraluminal air. CT is helpful in assessing
the relationships of fluid collections to adjacent thoracic or
Middle
mediastinum extrathoracic structures. It may play a role in guiding pro-
cedures to drain the mediastinal fluid collections.
Sympathetic
trunk, Cytologic features
ganglia, Spinal nerves Aspirates obtained from acute mediastinitis are fluid speci-
paraganglia Spinal ganglia
mens characterized by numerous neutrophils and purulent
Figure 12.1 Anatomy of mediastinum.
exudate, i.e., abscess. The aspirated material may be smeared
Diagnostic modalities directly on a slide, processed as a cytospin or LBC. Cell block
preparations provide tissue for special stains for organisms.
The development of minimally invasive techniques such as Some sample should always be submitted for culture.
image guided fine needle aspiration (FNA) or core biopsy
has largely replaced open surgical biopsy of mediastinal Chronic mediastinitis
tumors as the first diagnostic procedure. FNA or core biopsy Clinical features
of the masses of the middle and posterior mediastinum can Chronic mediastinitis can be granulomatous or sclerosing
be reached percutaneously under CT guidance or through fibrotic or a combination of the two. The typical location is
the esophagus with endoscopic ultrasound (EUS), and the superior/anterior mediastinum, in front of the tracheal
through the bronchus with endobronchial ultrasound bifurcation or at the lung hilum. Granulomatous mediasti-
(EBUS) or transbronchial with bronchoscope (TBNA), and nitis is most commonly due to fungal infection. Histoplasma
ultimately tissue biopsy via mediastinoscopy. The advan- is most common. Rare species include aspergillosis, crypto-
tages and disadvantages of various diagnostic modalities are coccosis, and mucormycosis (rhizopus). Mycobacterial
summarized in Table 12.1. infection, especially tuberculosis, is the second most com-
mon cause. See Chapter 43 for a detailed discussion of
LESIONS OF THE MIDDLE AND POSTERIOR infection.
MEDIASTINUM
Mediastinal cysts
Non-neoplastic mediastinal lesions Non-neoplastic cysts in the middle and posterior mediasti-
num are developmental cysts including pericardial cyst and
Acute mediastinitis foregut cysts. Foregut cysts are derived from an embryonic
Clinical features abnormality, with enterogenous cysts (50 to 70%) and bron-
Acute mediastinitis is usually bacterial and due to rupture of chogenic cysts (7 to 15%) being the most common subtypes.
organs in the mediastinum. Patients with acute mediastinitis In the middle mediastinum 61% of presenting masses are
present with chills, high fever, tachycardia, and chest pain. cysts. Pericardial and bronchogenic cysts are the second
The infection can progress rapidly with a high mortality most common masses of the middle mediastinum after
rate. Before the development of modern cardiovascular lymphomas. Esophageal and gastroenteric cysts are located
228
MIDDLE AND POSTERIOR MEDIASTINUM
Table 12.1 Diagnostic modalities of middle/posterior mediastinal lesions
Percutaneous
FNA and core
biopsy guided by Mediastinoscopy or thoracoscopy
CT/US EUS-FNA TBNA or EBUS-TBNA tissue biopsy
Advantages Access to virtually Lesions in lower paratracheal, Endobronchial lesions The standard of reference for pre-operative
any esphageal regions, subcarinal, associated with staging in non-small cell lung carcinoma. It
mediastinal aortopulmonary. Able to monitor enlarged lymph nodes allows direct visualization and sampling of
regions the biopsy in real-time adjacent to the airways mediastinal lesions
Disadvantages Inaccessible to lesions anterior to the TBNA: inability to Limited access to the posterior and inferior
trachea and the main bronchi and visualize the LN and mediastinum
anterior portion of the middle needle tip during Need general anesthesiaComplications in 1–
mediastinum sampling 3% of patients
EBUS-TBNA: Inaccessible
to subaortic and
paraesophageal lymph
nodes
Diagnostic FNA: 75–90% 82–96% TBNA: 25–81% 95–98%
accuracy Core bx: 94% EBUS-TBNA: 90–94%
Sensitivity FNA: 90% 92–93% EBUS-TBNA: 93–94% 92–98%
Core bx: 96%
Specificity FNA: 100% 97–100% EBUS-TBNA: 88–100% 100%
Core bx: 100%
Complications Pneumothorax:4– Solid lesions Hemoptysis, Hematoma Vascular injury, esophageal perforation,
60% 0–1% tracheobronchial injury, mediastinitis,
Hematoma Cystic lesion higher transcient Infection chylothorax, pericardial rupture,
Hemoptysis hypotention, postprocedure fever, pneumothorax, phrenic nerve injury,
infection, hemorrhages arrhythmias
FNA: fine needle aspiration; CT/US: CT scan/ultrasound; TBNA: transbronchial fine needle aspiration; EBUS: endobronchial ultrasound-guided fine
needle aspiration.
combination of the clinical and radiologic studies and

Table 12.2 Characteristics of mediastinal cysts
examination of cyst contents may allow a specific diagnosis
Type of cyst Location Cyst fluid Lining cells in some cases. EUS-FNA of mediastinal cysts with antibiotic
Pericardial Middle Watery Mesothelial prophylaxis can safely provide a definitive diagnosis in
Bronchogenic Middle/ Mucoid Respiratory/squamous atypical mediastinal cystic lesions. The location, features of
posterior ± cartilage cyst fluid, and lining cells of various mediastinal cysts are
Esophageal Posterior Mucoid Respiratory/squamous shown in Table 12.2.
Gastroenteric Posterior Bloody, Gastrointestinal
inflammation
Pericardial cyst
Clinical features
Pericardial cysts are an uncommon congenital anomaly in
in the posterior mediastinum. Children and adults have a the middle mediastinum. They represent 6% of mediastinal
similar incidence. Most mediastinal cysts are asymptomatic, masses, and 33% of mediastinal cysts. Pericardial cysts are
but children are more often symptomatic at discovery due to typically located close to the diaphragm, near the cardio-
compression on the surrounding structures. The cysts may phrenic angle, adjacent to the pericardium. They are usually
simulate a neoplasm on chest X-ray. FNA can demonstrate unilocular and solitary, but can be multiple, ranging from
the cystic nature of the lesion and relieve the compression. one to several centimeters in diameter. Patients are often
Although in many cases, the aspirates are paucicellular, asymptomatic and are identified in the fourth to fifth decade
containing only macrophages or inflammatory cells, the of life. The cysts are usually detected incidentally on chest
229
X-ray. Rare cardiac compression may occur, causing hemo- masses with a homogeneous density similar to water; how-
dynamic compromise. Excision via thoracotomy is an opti- ever, some bronchogenic cysts are mucoid and can give the
mal treatment for pericardial cysts, and percutaneous cyst impression of being a solid mass. Bronchogenic cysts are
aspiration may be, in selected patients, an attractive alter- non-enhancing, and, when there is a direct communication
native to surgery. Clinically asymptomatic patients may be with the tracheobronchial tree, air-fluid levels may be seen.
observed without intervention. MRI can differentiate the lesion from other masses.
Radiographic features Cytologic features

Pericardial cysts are well-circumscribed spherical or tear Aspirates of bronchogenic cysts contain clear, mucoid, or
drop-shaped masses that abut the heart, anterior chest opalescent fluid. Respiratory-type ciliated columnar cells
wall, and diaphragm. On CT scan, these masses appear as (Fig. 12.2A,E) or squamous metaplastic cells may be seen.
unilocular and non-enhancing cysts. If the wall of the cyst is sampled, cartilage (Fig. 12.2C),
smooth muscle, mucous glands (Fig. 12.2B,D), nerves, or
Cytologic features
focal calcification may be found. Bipolar, birefringent,
Aspirates mostly show a clear or straw colored watery fluid needle-shaped crystals, reminiscent of Charcot-Leyden
with a few chronic inflammatory cells. Pericardial cyst is the crystals, have also been described.
only mediastinal cyst that is lined by mesothelial cells.
However, the mesothelial lining cells are rarely present in Histologic features
the aspirate.
The walls of bronchogenic cysts are lined by ciliated pseu-
Histologic features dostratified respiratory epithelium or metaplastic squa-
Pericardial cysts are characterized by a simple, thin-walled mous cells and have focal areas of hyaline cartilage,
mesothelial-lined cyst wall composed of loose connective tissue. smooth muscle, and bronchial glands within their walls
(Fig. 12.2F).
Bronchogenic cyst
Clinical features Esophageal cyst
Bronchogenic cysts are the most common foregut cysts Clinical features
found in the middle mediastinum. They are closed sacs Esophageal cysts are much less common than bronchogenic
considered to be the result of an abnormal budding of the cysts and present within the wall of or in close association
tracheobronchial tree during embryonic development. with the esophagus. Embryologic duplication of specific
While it can be found at any age, it is more frequently elements of the esophageal wall causes cysts. Simple cysts
found in young adults. In the pediatric population, bron- are duplication of the epithelium, whereas true esophageal
chogenic cysts present with fever or dyspnea. Adults with duplications are duplications of the submucosa and the
bronchogenic cysts are usually asymptomatic. Patients with muscle wall without duplication of the epithelium. Most
large cysts may present with cough, dyspnea, stridor, dys- esophageal cysts develop in the right posteroinferior media-
phagia, or chest pain resulting from a mass effect on the stinum. Maldevelopment of the posterior division of the
trachea or esophagus. The management of infants and chil- primitive foregut is the embryologic defect responsible for
dren with bronchogenic cysts and adult patients with symp- esophageal cysts. The cysts are spherical and unilocular and
tomatic cysts is surgical removal. With the development of lined by stratified squamous epithelium with or without foci
more precise diagnostic techniques and a better understand- of ciliated columnar epithelium. The epithelium is sup-
ing of the variable natural history of these lesions, it is ported by the lamina propria with esophageal glands and
acceptable to treat asymptomatic bronchogenic cysts in surrounded by a double layer of smooth muscle, the lamina
adults in a conservative manner. Observation alone may be muscularis propria. Many children with esophageal cysts are
indicated for small, classic, asymptomatic cysts. asymptomatic. Most cysts are diagnosed during childhood.
Most adults (67%) with cysts are symptomatic. Chest pain
Radiographic features (tightness or fullness) is the most common presentation.
Bronchogenic cysts are spherical, usually unilocular but may Dysphagia may also occur. Hematemesis can occur if gastric
be multiloculated. These cysts are well-defined round epithelium is present in the cyst. Although rare, malignant
230
(A) (B) (C)
(D) (E) (F)
Figure 12.2 Bronchogenic cyst aspirated from a 9 cm posterior mediastinal mass of a 67-year-old man who presented with chest pain.
(A). Detached ciliated bronchial cells in mucoid background. Diff-Quik, 400× (B). Bubbly mucous gland. Diff-Quik, 400×. (C). Metachromatic
cartilage. Diff-Quik, 40×. (D). Mucous gland. Papanicoloau, 400×. (E). Many detached bronchial cells and rare mucous cells. Cell block. H&E, 400×.
(F). Histology of bronchogenic cyst showing ciliated respiratory epithelium-lined cystic cavity with submucosal mucous glands and hyaline
cartilage. H&E, 100×
transformation can occur. Plain chest radiographs can Histologic features

reveal a cyst within the mediastinum. Barium swallow stud- Esophageal cysts are differentiated from bronchogenic cysts
ies reveal compression of the esophagus without ulcer- by location, the presence of muscularis propria and the
ation. Nearly 75% of patients with esophageal cysts absence of cartilage.
eventually become symptomatic; therefore, cysts should
be surgically excised when they are diagnosed and Gastroenteric cyst
video-assisted thoracic surgery is the treatment of Clinical features
choice. Gastroenteric cyst is a rare developmental unilocular cyst
found in the posterior mediastinum, frequently connected
Radiographic features to the vertebral column with fibrous tissue. They are often
CT scan reveals a fluid-filled cystic structure originating found in infants as well as adults. Gastroenteric cysts are
from the esophagus. Endoscopy demonstrates extrinsic reported to be frequently associated with malformations of
compression with intact mucosa. Endoscopic ultrasonogra- the cervical and thoracic vertebrae such as hemivertebrae,
phy (EUS) reveals a cystic, fluid-filled structure in connec- posterior spina bifida, and scoliosis. Patients are sympto-
tion with the esophagus. MRI scans can also help in matic when diagnosed and present with pain due to com-
diagnosis of esophageal cysts. pression of nerves, peptic ulcers of the lining mucosa, and
other symptoms due to involvement of surrounding media-
Cytologic features stinal structures. Peptic digestion of the wall produces
Aspirates of esophageal cysts show squamous or ciliated sinuses and fistulae into the chest wall and thoracic
columnar cells, or both with mucoid fluid. organs and can be fatal. Development of adenocarcinoma
231
of the colonic type in gastroenteric cyst has been reported. schwannoma. Paraganglia associated with the sympathetic
Gastroenteric cysts are distinguished by their location and are chain give rise to paraganglioma. Neurogenic tumors com-
associated with congenital vertebral malformation. prise 40% of pediatric and 20% of adult mediastinal tumors.
Treatment of choice is usually surgical resection by In children, most neurogenic tumors are malignant arising
video-assisted thoracic surgery and should be individualized from sympathetic nervous system, whereas 95% of these
according to the symptoms and complications. tumors in adults are benign and more likely to be peripheral
nerve sheath tumors and paragangliomas. The benign neu-
Cytologic features rogenic tumors will be described first, followed by malignant
Aspirates obtained from gastroenteric cyst usually contain neurogenic tumors.
bloody fluid with inflammation. The cyst lining cells are
gastric, intestinal, or both types of epithelial cells. Clinical features
Many mediastinal neurogenic tumors are incidental findings
Histologic features during imaging studies of the thorax for unrelated issues.
Gastroenteric cyst is lined by either gastric mucosa with Symptoms are present in almost one-third of adult patients
parietal and chief cells; or small to large intestinal mucosa; and nearly two-thirds of the pediatric patients. In adults,
or squamous or ciliated columnar epithelium. Outside the asymptomatic mediastinal masses are more likely to be
mucosa, there are layers of muscularis mucosa, submucosa, benign. Symptoms associated with the respiratory tract,
and muscularis externa. including persistent cough, dyspnea, and stridor, predomi-
nate in pediatric patients because of the malleability of the
airway structures and the small size of the chest cavity.
Neoplastic mediastinal lesions
Constitutional symptoms, such as weight loss, fever, malaise,
Primary neoplastic mediastinal lesions are far less frequent and vague chest pain commonly occur with malignant
than secondary neoplastic lesions. The most common ori- tumors. Paravertebral tumors in the posterior mediastinum
gins of metastasis are lung and esophagus followed by are amenable to endoscopic removal, even in hard to reach
breast, thyroid, nasopharynx, larynx, kidney, testicular locations. Tumors with intraspinal extension can be removed
germ cell tumors, melanoma, and sarcomas. Small cell concurrently by performing a hemilaminectomy, followed by
carcinoma of the lung often appears as a huge mediastinal thoracoscopy, without the need for a thoracotomy.
mass in the presence of a small, radiographically undetect-
able bronchial lesion. Non-small cell carcinoma of the lung Neurofibroma
may also present as mediastinal mass, by direct extension Clinical features
or nodal metastases. Direct mediastinal extension can also Neurofibromas derive from axis-cylinder, endoneurium,
occur with tumors of esophagus, pleura, chest wall, verte- and nerve sheath tissues. These tumors are non-
bra, or trachea. Clinical history, imaging features, and encapsulated, thus mimicking a malignant tumor during
ancillary studies are usually helpful to reach a correct surgical procedures. Solitary neurofibroma rarely develops
diagnosis. See Chapter 10 for detailed description for meta- malignant transformation and surgical resection leads to
stastic tumors. cure. Multiple neurofibromas are often part of von
Recklinghausen’s disease, with approximately 8% of such
Neurogenic tumors cases undergoing malignant transformation.
Neurogenic tumors are the most common neoplasm of
the posterior mediastinum and may occasionally occur in Radiographic features
the middle mediastinum. As illustrated in Fig. 12.1, spinal Neurofibromas have infiltrative borders on CT scan and are
nerves and ganglions as well as sympathetic trunk and hypermetabolic on PET scan.
ganglions are all located in the paravertebral sulci in
the posterior mediastinum. Spinal nerves give rise to neuro- Cytologic features
fibroma, schwannoma, granular cell tumor, and Aspirates obtained from neurofibroma are characterized by
malignant peripheral nerve sheath tumor (MPNST). sparse large cohesive fragments of mesenchymal tissue with
Sympathetic nervous system gives rise to neuroblastoma, haphazardly oriented spindle nuclei reminiscent of “carrot
ganglioneuroma, ganglioneuroblastoma, and melanotic peels” in a loose connective tissue matrix (Fig. 12.3A,B). The
232
(A) (C)
(B) (D)
Figure 12.3 Neurofibroma aspirated from paraspinal mass of a 60-year-old female. (A). Cohesive fragment of spindle cells in lightly metachromatic
matrix. Diff-Quik, 100×. (B). Cohesive fragment of neoplastic spindle cells. Papanicolaou, 100×. (C). Comma-shaped nuclei haphazardly arranged like
“carrot peels” in a loose fibrillar connective tissue stroma. Papanicolaou, 1000×. (D). Histology of neurofibroma showing unencapsulated tumor with
haphazardly arranged spindly cells in a loose fibrillar connective tissue stroma. H&E, 100×.
From Yang GCH, Tao L-C. Transabdominal Fine-Needle Aspiration Biopsy. A Color Atlas and Monograph (with CD.ROM); 2007, Copyright 2007
Reproduced with permission from World Scientific Publishing Co. Pte. Ltd.
nuclei are elongated with a wavy, serpentine shape and The cells are intimately associated with wire-like strands of
pointed ends (Fig. 12.3AC). The cytomorphology of neuro- collagen that have been likened to “shredded carrots.” Small
fibromas is similar to their histology except it is three- to moderate amount of mucoid material separate the cells
dimensional in aspirates. Unlike schwannomas, there is no and collagen.
palisading or parallel arrangements of the spindly nuclei.
Ancillary techniques
Key cytomorphologic features: neurofibroma
S-100 immunoexpression is more focal and less intense than
* Hypocellular aspirate with large cohesive clusters that of schwannomas. Neurofilament is positive and fibro-
of wavy spindle cells in an amorphous myxoid stroma blasts are CD34 positive in neurofibromas.
* Elongated, comma-shaped nuclei with evenly distrib-
uted, finely granular chromatin Schwannoma
* Background mucoid material may contain small frag- Clinical features
ments of collagen bundles Schwannomas (neurilemmoma) are encapsulated. Such
tumors originate from Schwann cells. They grow slowly
Histologic features and regressive changes within such tumors (e.g., fatty
Neurofibromas are characterized by interlacing bundles of change and cystic formation) are common. In the cases of
elongated cells with wavy, dark-staining nuclei (Fig. 12.3D). cystic Schwannoma, the cavities were filled with inspissated
233
(A) (C)
(B) (D)
Figure 12.4 Schwannoma, cohesive type, aspirated from the paraspinal area of a 30-year-old female. (A). Cohesive mesenchymal tissue fragments
in a clean background. Diff-Quik, 100×. (B). Cohesive mesenchymal tissue with spindly nuclei in haphazard arrangement. Papanicolaou, 100×.
(C). Bland spindly nuclei associated with stroma. Papanicolaou, 400×. (D). Histology of schwannoma showing encapsulation spindle cell tumor with
Antoni A and Antoni B areas. H&E, 100×.
proteinaceous fluid or a gelatin-like material. Schwannomas may be observed in cell block preparation. In the aspirates
are usually solitary and exceedingly rarely malignant, dif- of ancient schwannoma (Fig. 12.6A–C), some of the nuclei
fuse, prominent cytologic atypia, or mitoses suggest malig- are large and hyperchromatic, which represents degenera-
nant change. tive change. If a cytologic specimen has been aspirated from
a cystic cavity of the tumor, the fluid in aspirate smears takes
Radiographic features the form of finely granular debris, resembling caseating
On CT scan, schwannomas typically present as circum- necrosis from a tuberculous lesion. Collections of foamy
scribed mass, and on PET scan, have a high level of FDG macrophages are often seen. Differential diagnoses include
uptake. ganglioneuroma and neurofibroma. The former has gan-
glion cells, while the latter can produce some palisading
Cytologic features effect but usually the cells are similar to fibroblasts and do
Aspirates obtained from schwannomas are characterized not produce the characteristic Verocay bodies.
by numerous spindle cells in both cohesive groupings
(Fig 12.4A–C), or loose groupings (Fig. 12.5ABC). Their Key cytomorphologic features: schwannomas
nuclei are ovoid, elongated, or spindle-shaped with pointed * Variable cellularity with large thick fragments, smaller
ends and are often arranged in a parallel or palisading clusters, and single spindle cells
fashion. Fine fibrillary matrix (Fig. 12.5B) between nuclei * Characteristically cellular Antoni A tissue fragments and
may be seen in smear preparations. Cell structures that degenerative/myxoid Antoni B tissue fragments with
resemble the Verocay bodies seen in histologic sections scant spindle cells often present
234
(A) (C)
(B) (D)
Figure 12.5 Schwannoma aspirated from a paraspinal mass in a 66-year-old female. (A). Spindly nuclei enmeshed in metachromatic fibrils. Diff-
Quik, 400×. (B). Bland spindly nuclei with pointed ends in finely fibrillar background. Unlike neurofibroma, there is no loose connective tissue stroma.
Note the twisted appearance of some nuclei. Papanicolaou, 400×. (C). The fibrillary cytoplasm is immunoreactive to S-100, which was applied directly
on a Papanicolaou-stained smear (400×). (D). Histology of schwannoma shows palisading rows of spindly nuclei (Verocay body). H&E, 100×.
* Tumor cells are spindle-shaped with tapering ends. Nuclei Ancillary techniques
are uniform in size and oval with rounded ends and fine Immunohistochemistry is helpful in the specific diagnosis of
chromatin. No distinct nucleoli or small single nucleoli schwannomas. Tumor cells strongly and diffusely express
* Ill-defined, fragile cytoplasm, easily stripped, forming S-100, negative for fibroblast marker CD34 and negative for
fibrillary ground substance neurofilaments.
Histologic features Granular cell tumor

Unlike neurofibroma, schwannomas are encapsulated Clinical features
(Fig. 12.4D) and are characterized by Antoni A and Granular cell tumor (GCT) is a common peripheral nerve
Antoni B areas (Fig. 12.5D). Antoni type A area consists of sheath tumor characterized by abundant granular cyto-
bands of spindle cells with the nuclei in a parallel or polar plasm. It can occur in posterior mediastium. The over-
arrangement, which sometimes form characteristic Verocay whelming majority of granular cell tumors are benign.
bodies, where tumor cell nuclei are arranged in parallel Malignant granular cell tumor is a well established but rare
stacks. Antoni type B area consists of loose myxoid cystic entity, with fewer than 100 reported cases in the literature
spaces that contain the proteinaceous material. Histology of and constitutes fewer than 2% of granular cell tumors in the
ancient schwannoma is shown in Fig. 12.6D. literature. Malignant GCTs tend to be larger. A history of
235
(A) (C)
(B) (D)
Figure 12.6 Ancient schwannoma, aspirated from a 19-year-old female with a 3 cm cystic paraspinal mass. The FNA diagnosis was confirmed by
surgical excision 3 months later. (A). Low power of the aspirate smear shows cohesive fragments of stromal tissue. Papanicolaou, 100×. (B). Large nuclei
(arrow) interspersed among small nuclei. Papanicolaou, 1000×. (C). Metachromatic mesenchymal tissue studded with large and small nuclei. Diff-
Quik, 400×. (D). Histology of ancient schwannoma showing atypical nuclei secondary to degenerated changes. Resected tumor. H&E, 400×.
long clinical duration and recent rapid growth in some cases in shape. The tumor cells may burst upon smearing, releas-
suggests malignant transformation from a pre-existing ing stripped nuclei and granular material in the background.
benign GCT. Clinically, this tumor occurs in patients of Occasional cells with nuclear pleomorphism and small but
any age, but is most common in the fourth to sixth decades conspicuous nucleoli can occur. In a study of three malig-
of life. It is twice as common in women than men. Black nant GCT and 17 benign GCT, Wieczorek et al reported
patients outnumber white patients by a considerable mar- malignant GCTs have typical cytologic features, including
gin. Grossly, GCT has infiltrative margins and is closely increased N/C ratio, spindle nuclei, hyperchromasia, coarse
associated with peripheral nerves. chromatin, nuclear pleomorphism, or vesicular nuclei with
enlarged nucleoli. However, morphologic heterogeneity
precludes definitive classification of some tumors by cyto-
Granular cell tumors have infiltrative borders on CT scan
logic features alone. A multifocal GCT of the esophagus with
and increased accumulation of FDG on PET scan.
gastric metastasis showing spindly nuclei is shown in
Cytologic features Fig. 12.7. Differential diagnosis of GCT include rhabdo-
Aspirates obtained from GCT are cellular and composed of myoma and fibroxanthomas and any cells with abundant
large, polygonal cells with granular cytoplasm forming syn- granular cytoplasm may look like GCT. However, only GCT
cytium (Fig. 12.7A–C). The nuclei are round to slightly oval cells have invisible cell borders on light microscopy.
236
(A) (C)
(B) (D)
Figure 12.7 Granular cell tumor aspirated from a 30-year-old black female with progressive constriction of esophagus since age 20. The tumor was
found at multiple foci along the esophagus and was also present in the stomach at the time of surgery. (A). Spindly nuclei associated with metachromatic
cytoplasm. Diff-Quik, 100×. (B). Spindly nuclei in abundant cytoplasm, wrapping around atrophic skeletal muscle. Papanicolaou, 400×. (C). Spindly
nuclei in abundant granular cytoplasm with invisible cell borders. Papanicolaou, 1000×. (D). Histology showed syncytium of spindly nuclei in abundant
eosinophilic granular cytoplasm. Resected tumor. H&E, 400×.
Key cytomorphologic features: granular cell tumor ultrastructural features of Schwann cells with long cytoplas-
mic processes and basal lamina, but the cytoplasm is dis-
* Abundant granular cytoplasm with indistinct cell bor-
tended by numerous phagolysosomes.
ders, forming syncytium
* Cytoplasm is metachromatic in Diff-Quik, gray in Ancillary techniques
Papanicolaou, and eosinophilic in H&E Immunohistochemistry is helpful in the specific diagnosis
* Round to oval bland nuclei in benign GCT, spindly of GCT. GCTs show diffuse cytoplasmic staining for S-100,
nuclei or markedly atypical nuclei in malignant GCT NSE, leu-7, inconsistent expression of vimentin, and nega-
tive staining for cytokeratins.
Histologic features
As shown in Fig. 12.7D, GCT are characterized by ribbons Ganglioneuroma
or nests of eosinophilic tumor divided by slender fibrous Clinical features
connective tissue or in large sheets. The tumor cells are Ganglioneuromas represent the fully differentiated mem-
rounded, polygonal, or slightly spindled with nuclei ranging bers of the neuroblastic tumors and are invariably benign.
from small and dark to large with vesicular chromatin. They occur in old individuals. They can be multiple. Similar
Malignant granular cell tumor shows spindling nuclei and to ganglioneuroblastomas, they occur much more fre-
cytoplasm and nuclear atypia. The tumor cells have the quently in posterior mediastinum and retroperitoneum
237
(A) (C)
(B) (D)
Figure 12.8 Ganglioneuroma aspirated from an 18-year-old female with a T3-5 spinal mass in the posterior mediastinum. (A). Cohesive spindly
stroma containing ganglion cells (arrow). Diff-Quik, 100×. (B). Ganglion cells popped out from the schwannian stroma by the smearing. Papanicolaou,
100×. (C). Some of the ganglion cells are binucleated. Ganglion cells without the spindle cell stroma are sometimes misinterpreted as oncocytic cells.
Papanicolaou, 400×.(D). Histology of ganglioneuroma shows ganglion cells within the schwannian spindly stroma. Resected tumor. H&E, 100×.
than adrenal medulla. These tumors are encapsulated and out of the mesenchymal tissue as isolated cells (Fig. 12.8B,
curable by excision. Catecholamine synthesis by the gan- C) by the force of smearing. Some ganglion cells are gigan-
glions is an almost constant feature of all tumors, and, in tic and have large round or ovoid nuclei, prominent nucle-
most cases, catecholamine precursors and metabolites can oli, and an abundance of dense cytoplasm. Other ganglion
be demonstrated in the urine. cells have several peripherally placed nuclei. Occasional
loose groups of maturing ganglion cells with relatively
scanty cytoplasm may also be present. The elongated or
Ganglioneuromas typically are incidental findings of space- spindle-shaped nuclei of spindle Schwannian stroma are
occupying posterior mediastinal masses during radiologic often in parallel or polar arrangements. The fibrillary
study for other causes. On PET/CT scan, ganglioneuromas material between elongated or spindle-shaped nuclei
are weakly FDG avid lesions. resembles that seen in schwannomas. The differential diag-
Cytologic features nosis is schwannoma, if ganglion cells are hidden within
the spindly stroma.
Aspirates obtained from ganglioneuromas are characterized
by ganglion cells embedded within spindle cell stroma
Key cytomorphologic features: ganglioneuroma
(Fig. 12.8A). Like all mesenchymal tumors, ganglioneuroma
are challenging to aspirate by inexperienced aspirators. The * Large cohesive fragment of spindly mesenchymal tissue
large fragment of mesenchymal tissue in the aspirates * Scattered ganglion cells
frequently masks ganglion cells. Ganglion cells may pop * Spindly schwannnian stroma containing ganglion cells
238
Histologic features to rubbery consistency. They are highly vascular tumors and
may have a deep red color grossly.
Ganglioneuromas are characterized by islands of ganglion
The majority of these neoplasms are benign. Malignant
cells, which may be multinucleated, surrounded by neurom-
and benign paragangliomas may have similar microscopic
atous stroma (Fig. 12.8D)
appearances. Diagnosis of malignant paraganglioma is
Ancillary techniques based on clinical behavior, i.e., distant metastasis or invasive
destructive growth pattern. Metastases occur most frequently
Ganglion cells are positive for neuroendocrine antigens and
in the regional lymph nodes, liver, lungs, and bones.
Schwannian stroma are positive for S-100. However, immuno-
However, clinical and pathologic evidence of malignancy
histochemistry is unnecessary in diagnosing ganglioneuroma.
often develops years after resection of the original tumor.
Paraganglioma Radiographic features
Clinical features Paragangliomas appear as homogeneous or heterogeneous
Paragangliomas arise from paraganglia associated with the hyperenhancing soft tissue mass at CT scan, multiple areas of
sympathetic chain and may occur anywhere along the mid- signal void interspersed with hyperintense foci (salt and pepper
line of the posterior mediastinum. Such tumors may secrete appearance) within tumor mass at MRI, and an intense tumor
epinephrine and/or norepinephrine. Patients with function- blush with enlarged feeding arteries at angiography. FNA is
ing tumors may have paroxysmal or persistent hyperten- contraindicated if paraganglioma is suspected clinically.
sion, orthostatic hypotension, palpitation, headaches, and
flushing or sweating spells in various combinations. The Cytologic features
paragangliomas appear grossly as sharply circumscribed, Aspirates obtained from unsuspected paragangliomas are
well or partially encapsulated, polypoid masses with a firm characterized by tumor cells in loose groupings (Fig. 12.9)
(A) (C)
(B) (D)
Figure 12.9 Paraganglioma aspirated from a 10 cm left-sided, subcarinal posterior mediastinal mass of a 22-year-old female with paroxysmal
tachycardia. (A). Loosely cohesive ovoid nuclei. NucleI,2–5× RBC. Diff-Quik, 400×. Inset: Red neuroendocrine granules in the cytoplasm. Diff-Quik,
1000×. (B). The cells are connected by long cytoplasmic processes. Papanicolaou, 400×. (C). Anisonucleosis and long cytoplasmic tails. Papanicolaou,
1000’. (D). Histology of paraganglioma showing “Zellballen” of tumor wrapped by blood vessels. Resected tumor. H&E, 100×.
239
(A) (C)
(B) (D)
Figure 12.10 Paraganglioma aspirated by an experienced radiologist with a 22-gauge Turner needle with rotating motion, resulting in tissue
fragments. (A). “Zellballen” pattern with tumor nests outlined by vascularized septa. Arrow point to the sustentacular cells stretching out at periphery.
Papanicolaou, 100×. (B). The tumor cells have moderate amounts of granular cytoplasm. Papanicolaou, 400×. (C). Note syncytial appearance due to
indistinct cell borders. Papanicolaou, 400×. (D). Histology showing “Zellballen” pattern. Resected tumor. H&E, 100×.From Yang GCH, Tao L-C.
Transabdominal Fine-Needle Aspiration Biopsy. A Color Atlas and Monograph (with CD.ROM); 2007, Copyright 2007 Reproduced with permission
from World Scientific Publishing Co. Pte. Ltd.
and, less frequently, in cohesive fragments of syncytial cells is shown in Fig. 12.11. The interconnecting cytoplasmic
with attached sustentacular cells similar to their histology processes can be seen as well (Fig. 12.11C). The differential
(Fig. 12.10). In the latter case, the experienced radiologist diagnosis includes other neuroendocrine tumors, which can
routinely rotates a 22 gauge Turner needle during aspira- be excluded by cytokeratin immunoreactivity.
tion. The tumor cells were round to oval, plasmacytoid and
spindled, and seen as scattered, in clusters, acinar and peri- Key cytomorphologic features: paraganglioma
vascular pattern. The most consistent feature was the pres- * Loosely cohesive or single cells with round to oval nuclei
ence of pink granules in Wright-Giemsa stained smears. with plasmacytoid and spindled cytoplasm
However, the granules are less obvious in Diff-Quik stain * Interconnecting cellular processes can be seen in direct
(Fig. 12.9A, inset). Anisokaryosis, a feature for neuroendo- smear free of obscuring red blood cells
crine cells, is also present in paraganglioma. The ultrastruc- * Pink cytoplasmic granules seen in Wright-Giemsa stain
tural feature of interconnecting cytoplasmic processes was * Variation in nuclear size (anisonucleosis)
recently reported in cytologic smears. Based on a study of six
paragangliomas, Gonzalez-Campora et al reported that par- Histologic features
adoxically, malignant paragangliomas show less anisokar- Paraganglioma are characterized by polygonal to oval tumor
yosis than do their benign counterparts. An example of cells, arranged in distinctive cell balls, termed “Zellballen”
malignant paraganglioma aspirated from the lung 11 years (Figs.12.9D to 12.11D). Cytoplasm is variable but often at
following resection of a paraganglioma thought to be benign least moderate in volume, and is frequently distinctly
240
(A) (C)
(B) (D)
Figure 12.11 Malignant paraganglioma aspirated from the lung of a 45-year-old man, 11 years post resection of paraganglioma. (A). Loosely
cohesive tumor cells with rare multinucleated cells in a bloody background. Diff-Quik, 100×. Inset: Rare multinucleated cell. Nuclei ~2–4 ×RBC. Diff-
Quik, 400×. (B). Interconnecting cytoplasmic processes. Papanicolaou, 100×. (C). The cells are connected by elongated cell processes. Papanicolaou,
400×. (D). Histology showed vague “Zellballen” pattern. Resected tumor. H&E, 200×.
granular. Their nuclei, although variable in size, are often 1 (NF1). About 10% of patients with NF1 present with
perfectly round, with or without nucleoli. These cell balls are MPNST, usually after a latent period of 10 to 20 years.
separated by fibrovascular stroma and surrounded by sus- Sporadic MPNST also exists. The median age at diagnosis of
tentacular cells. MPNST in NFl patients was 26 years, compared to 62 years in
patients with sporadic MPNST. The 5-year survival from
Ancillary techniques diagnosis was 21% for NFl patients with MPNST, compared
Immunohistochemistry can confirm the diagnosis of para- to 42% for sporadic cases of MPNST. Overall 5 year survival is
ganglioma. The tumor cells are negative for cytokeratins, about 50%, but it decreases to only 15% for tumors involving
while positive for neuroendocrine markers, i.e., chromog- the trunk. A high rate of local recurrence is caused by the
ranin, synaptophysin, and CD56. The sustentacular cells peculiar ability of the tumor cells to spread along nerve sheaths.
are S-100.
Malignant peripheral nerve sheath tumor CT scan and MRI can identify some malignant features such
Clinical features as a large infiltrative mass with irregular border and necrotic
Malignant peripheral nerve sheath tumor (MPNST) rarely and heterogeneous contrast enhancement. However, these
occur in the posterior mediastinum. It is often large and radiographic features are non-specific, which makes the
symptomatic when detected, compressing, displacing, or CT scan and MRI unreliable in accurately characterizing
invading the intrathoracic organs and thoracic wall. Most a lesion as benign or malignant. PET is very sensitive in
such tumors develop in patients with neurofibromatosis detecting MPNST in patients with NF1. However its
241
(A) (C)
(B) (D)
Figure 12.12 Malignant peripheral nerve sheath tumor, spindle cell type, aspirated from the lung of a 46-year-old man with resection of
atypical schwannoma. (A) Loosely cohesive and fragments of spindly nuclei. Diff-Quik, 40×. (B). Spindly nuclei in metachromatic background
substance. Diff-Quik, 100×. (C) Fibrillary background in an area of high cellularity. Papanicolaou, 100×. Inset: Bland spindly nuclei. Papanicolaou,
400×. (D). Histology of MPNST showed marked hypercellularity and the high mitotic activity in the absence of significant pleomorphism of spindle
cells in fascicles. H&E, 100×.
specificity for MPNST in NF1 is only 70–80%. CT scans, Key cytomorphologic features: malignant peripheral
MRI, and PET are not specific alone for differentiating nerve sheath tumor
between benign and malignant neurogenic tumors but * Hypercellular aspirate co00mposed of spindly tumor
used in conjunction can improve the diagnosis. cells in aggregates and singly, less frequently, epithelioid
cells or pleomorphic cells
Cytologic features * Myxocollagenous stroma in Diff-Quik stain
In FNA smears, there are three types of MPNST. (1) Spindle * Indistinct cell borders with delicate and fibrillary cyto-
cell type (Fig. 12.12A–C). The spindle cells have comma-like plasm with tapering
naked spindly nuclei in a fibrillary matrix with increased * Nuclear shape varies from ovoid to elongated, comma-
cellularity. (2) Anaplastic type (Fig. 12.13A–C) with pleo- shaped, serpentine to pleomorphic
morphic cells in addition to spindle cells. (3) Epithelioid
type with eccentric nuclei and well-defined round to polyg- Histologic features
onal cytoplasm. The loss of cohesion with many individual Most MPNSTs resemble fibrosarcomas or other spindle cell
intact tumor cells is helpful in distinguishing benign and sarcomas in their overall organization (Figs. 12.12D and
malignant peripheral nerve sheath tumors. 12.13D). Specific categorization without immunhistochemistry
242
(A) (C)
(B) (D)
Figure 12.13 Malignant peripheral nerve sheath tumor, anaplastic type. (A). Cohesive mesenchymal tissue fragments rimmed by single cells
attached to the tumor fragment. Diff-Quik, 40×. (B). Metachromatic matrix between pleomorphic nuclei. Diff-Quik, 400×. (C). Large spindle and
convoluted nuclei (arrow) with fibrillary cytoplasm with invisible cell borders. Papanicolaou, 400×. (D). Histology of resected tumor showing cellular
Antoni A area on the right and less cellular Antoni B area on the left. H&E, 100×.
is possible only when some of the schwannian features can be interdigitating dendritic cell sarcomas express histiocytic
recognized. Heterologous elements, such as cartilage, bone, markers (CD68, CD163) to some degree.
skeletal muscle, and mucin-secreting glands, are more com-
mon in MPNST than in other sarcomas. A small portion of Melanotic schwannoma
MPNSTs closely resemble neurofibromas, except that they Clinical features
have a higher cellularity and, most importantly, mitotic activ- Melanotic schwannoma is a rare malignant tumor that orig-
ity, or high proliferation index. inates from the sympathetic chain and is closely related to
neural crest-derived pigmented cells in other parts of the
Ancillary techniques body. In the trunk, neural crest cells give rise to pigmented
MPNST is diffusely positive for vimentin. S-100 reactivity is cells, sympathetic ganglion and dorsal spinal ganglion, and
variable. In 50–70% of MPNSTs, scattered tumor cells adrenal medulla. There are two types of melanotic schwan-
express S-100 protein. Immunoexpression for p53 is present noma: the sporadic type and the psammomatous type of
in a majority of MPNSTs. High Ki67 proliferation index is Carney complex. The dorsal location represents 30.5% of the
also present. spinal melanotic schwannoma. In a review of 47 spinal mel-
Most spindle cell neoplasms can be excluded by S-100 anotic schwannomas in the literature, De Cerchio reported
positivity, except for spindle cell melanoma and interdigitat- patients’ age ranged from 12 to 70 (mean 40 years) with slight
ing dendritic cell sarcoma. Many spindle cell melanomas female predominance. The clinical presentation is radicular
lack expression for melanocytic markers, thus clinical pain, dysesthesias, progressive sensorial-motor deficits.
history is important. In addition to S-100 positivity, Grossly, melanotic schwannomas are well-circumscribed or
243
encapsulated and vary from black-brown to gray-blue, clusters, with ill-defined boundaries. Cytologically, the differ-
depending on the amount of melanin pigments. Prognosis ential of melanotic schwannoma is spindle cell melanoma.
of melanotic schwannoma is usually poor. It may recur or Both are dyscohesive and spindly. However, the cytoplasmic
metastasize after more than 5 years, even in the absence of processes of melanotic schwannoma are thread-like, longer,
overt malignant morphological features. Only one of five and more slender.
patients had no recurrence and was free of disease 6 years
after initial diagnosis. Marco et al reported two patients with Key cytomorphologic features: melanotic
melanotic schwannoma, one was located in the neck and the schwannoma
other in the mediastinum. Both patients died from metastasis. * Solitary and loosely cohesive groupings
* Large ovoid nuclei (~5–8× RBC) and “thread-like” long
Radiographic features and narrow cytoplasmic processes
PET scan shows increased metabolic activity with stand- * Melanin pigments present in many, but not all, of the
ardized uptake of 6.4 (normal range < 1.5) spindly cells
Cytologic features Histologic features

Aspirates obtained from melanotic schwannoma are charac- Melanotic schwannoma are characterized by variation in
terized by: (1) solitary spindle cells with polarized nucleus and cell shape from polygonal to spindled and blend gradually
thread-like tapered, very long and thin cytoplasmic ends into one another. This feature, coupled with the ill-defined cell
(Fig. 12.14A–C); (2) large three-dimensional clusters with borders often imparts a syncytial quality. Occasionally, there is
heavy melanin deposits; and (3) loose syncytial monolayered vague palisading or formation of whorled structures that are
sheets without melanin deposit. The cells were arranged in reminiscent of a schwannoma or neurofibroma (Fig. 12.14D).
(A) (C)
(B) (D)
Figure 12.14 Melanotic schwannoma of the posterior mediastinum in a 23-year-old female who later developed liver metastasis. (A). Tadpole-like
cells with oval nuclei and green-black pigments and long wavy tails. Nuclei 7–8× RBCs. Diff-Quik, 400×. (B). Discohesive spindle cells with ovoid
nucleus and bipolar long, thin, and wavy cytoplasmic processes. Amelanotic cells interspersed with melanotic cells in this field. Papanicolaou, 400×.
(C). Oval bland nuclei and cytoplasm filled with brown melanin pigments. Papanicolaou, 1000×. (D). Histology of melanotic schwannoma, showing a
vague palisading or formation of whorled structures that are reminiscent of a schwannoma in lightly pigmented areas. Resected tumor. H&E, 100×.
244
The degree of melanin pigments varies and usually, there are posterior mediastinum and retroperitoneum than adrenal
focal areas with no melanin pigment deposits. medulla. Most tumors are seen in young children, but may
occur in adults.
Immunohistochemistry is helpful in the specific diagnosis of Radiographic features
melanotic schwannoma. Melanotic schwannomas coexpress These tumors are often encapsulated and have a lobulated
S-100 and HMB45 in the cytoplasm and laminin and collagen appearance. Focal deposits of calcium are commonly seen.
IV mark the basal lamina outline of the spindly neoplastic cells.
Ultrastructurally, melanosome-containing cells with elongated Cytologic features
cell processes and duplicated basal lamina were present. Aspirates obtained from ganglioneuroblastomas are
characterized by neuroblasts and ganglion cells coexist in a
Ganglioneuroblastoma background of fibrillary neuropils (Fig. 12.15A–C). The
Clinical features neuroblasts are intermingled with much larger ganglion
Ganglioneuroblastomas are neuroblastic tumors of inter- cells in different stages of maturation from differentiated
mediate malignancy potential, and have a degree of differ- neuroblasts. The amount of spindly schwannian stroma is
entiation that is intermediate between ganglioneuroma and variable, since they are more difficult to aspirate and may be
neuroblastoma. The tumor occurs much more frequently in underrepresented in aspiration samples.
(A) (C)
(B) (D)
Figure 12.15 Ganglioneuroblastoma aspirated from a 16-year-old female. (A). Two Homer-Wright rosettes among neuroblasts. Notice the spindly
schwannian stroma is absent in this aspiration sample. Diff-Quik, 40×. (B). Neuroblasts and scattered ganglion (arrow) in a background of fibrillary
neuropils (inset). Papanicolaou, 100×. (C). Ganglion cell and neuroblasts separated by smearing. Papanicolaou, 400×. Inset ganglion from B.
(D). Histology of ganglioneuroblastoma showed nests of intermixed ganglion cells and neuroblast cells and intervening spindly schwannian stroma.
Resected tumor. H&E, 100×.
Reproduced with permission from World Scientific Publishing Co. Pte. Ltd
245
Key cytomorphologic features: ganglioneuroblastoma treatment, and the overall 2-year survival rate is about 60%.
* Ganglion cells are large cells with abundant cytoplasm However, survival rates depend on a number of factors
containing nuclei with prominent nucleoli. Binucleated including the age of the child at the time of diagnosis,
ganglion cells may be present stage of the disease, location, and degree of histologic differ-
* Ganglion cells scattered among small neuroblastoma entiation of the tumor.
cells among neuropils
Cytologic features
* In aspiration sample, schwannian stroma may be
underrepresented Aspirates obtained from neuroblastoma are characterized
by small tumor cells in loose groupings and as solitary cells.
They have very little or no recognizable cytoplasm and have
Histologic Features small round, ovoid, spindle, or irregularly shaped nuclei
Ganglioneuroblastoma is subdivided into two groups: nodu- with coarsely clumped chromatin and indistinct nucleoli.
lar and intermixed. The former is composed of grossly visible Tumor cells in rosette or organoid arrangements may be
nodules of pure neuroblastoma cells, surrounded by ganglio- seen (Fig.12.16ABC). The tumor cells are often situated in
neuromatous background; the latter is composed of neuro- variable amounts of eosinophilic fibrillary material which
blastoma cells intimately mixed with the ganglioneuromatous corresponds to the neuropil. Differential diagnoses in
background. The intermixed group has a better prognosis pediastric patients include primitive neuroepidermal
than the nodular group, because the nodules represent foci tumor (PNET), lymphoma, and rhabdomyosarcoma.
of rapidly proliferating neuroblasts. Histology of ganglioneur- Rhabdomyosarcoma cells do not form rosettes.
oblastoma of intermixed type is shown in Fig. 12.15D. Lymphoma cells shed“lymphoglandular bodies” in Diff-
Quik stained smears. Immunohistochemically, both neuro-
blastoma and PNET are positive for NSE; however, PNET
Immunohistochemistry is not needed in diagnosing are immunoreactive to CD99 as well, and show character-
ganglioneuroblastomas. istic cytogenetic translocation of t(11;22)(q24;q12).
Neuroblastoma Key cytomorphologic features: neuroblastoma

Clinical features * Hypercellular aspirate consists of small, rigid, blue cells
Neuroblastomas are highly aggressive tumors and 80% of with high N/C ratio arranged singly or in groups in the
the patients are younger than 5 years. Rarely, it can occur absence of “lymphoglandular bodies” or nuclear molding
in adults. Over 25% occur in adrenal medulla, and the * Occasional Homer-Wright rosettes
remainder along the sympathetic chain. Frequencies along * A fibrillar background resembling neuropils
the sympathetic chain include: neck (1%), mediastinum
(19%), abdomen (30% non-adrenal), or pelvis (1%). Histologic features
Neuroblastomas arise from the primitive neuroblasts in Neuroblastoma are characterized by small cells with little,
sympathetic ganglia. These tumors frequently contain foci poorly defined cytoplasm and 25–35% have Homer-
of calcification which can be visualized during imaging Wright pseudorosettes (Fig. 12.16D). The tumor may
studies. In most cases, an elevated level of catecholamines have alveolar or pseudovascular appearance due to hem-
can be demonstrated in patients’ urine. Thirty per cent of orrhage and may have prominent calcification and necrosis
neuroblastomas regress or mature into ganglioneuroma. As is common. Ultrastructurally, the neuroblasts contain neu-
the neuroblasts mature toward ganglions, Schwann cells rosecretory granules with synaptic endings. Neuropils are
appear and start to myelinate the axons, producing schwan- unmyelinated axons containing neurofilaments and
nian stroma. Grossly, neuroblastomas are non-encapsulated microtubules. The center of Homer-Wright pseudorosettes
and infiltrate surrounding tissue. Neuroblastoma and gan- is composed of a complex interdigitating meshwork of
glioneuroblastoma diagnosed at an early stage of disease neuropils.
may be treated with primary resection. Advanced stages of
these diseases are treated primarily with chemotherapy, and Ancillary techniques
surgical resection is rarely indicated. The prognosis of Immunohistochemistry is helpful to confirm neuroblas-
patients with neuroblastoma is poor, in spite of aggressive toma. Tumor cells are negative for CD99 or cytokeratins
246
(A) (C)
(B) (D)
Figure 12.16 Neuroblastoma aspirated from a 5-year-old boy. (A). Numerous neuroblasts, with scattered pseudorosettes in meshwork of neuritis.
Diff-Quik, 40×. (B). Pseudorosette (arrow) in meshwork of neuritis. Papanicolaou, 100×. (C). Hyperchromatic nuclei with no visible nucleoli in
neuroblasts, Papanicolaou, 400×. (D). Histology of neuroblastoma showing Homer-Wright pseudorosette with fibrillary center. H&E, 400×.
and positive for neurofilament and neuroendocrine markers and specific t(11;22)(q24;q12) chromosomal translocation
such as NSE and chromogranin. with Ewing sarcoma. The breakpoints involve the EWS gene
on chromosome 22 and the FLI-1 gene on chromosome 11.
Primitive neuroectodermal tumors
Clinical features Radiographic features
Primitive neuroectodermal tumor (PNET) of thoracopul- PNET of the thoracopulmonary region typically presents as
monary region was first reported by Askin et al in a series of a soft tissue mass with or without pleural or rib involvement,
in 20 children and adolescents (average age 14.5 years;. 75% often with metastatic disease to the skeletal system, bone
of the patients were females. The neoplasm tended to recur marrow, thorax, and sympathetic chain.
locally and did not seem to disseminate as widely as some of
the other small cell tumors of childhood. In a series of 10 Cytologic features
patients with Askin tumor (PNET of thoracopulmonary Aspirates obtained from PNET are characterized by numer-
region), Fink et al reported the age range from 11 to 33 ous small uniform cells without nuclear streaking in loose
years (mean 18 years). Clinically, it presents as a chest wall groupings and singly (Fig. 12.17ABC). The neoplastic
mass with or without pain. Standard therapy includes en cells have solitary small, round to ovoid nuclei. Scanty
bloc resection, with accompanying radiotherapy and chemo- basophilic cytoplasm with or without vacuoles can be
therapy if complete resection is not possible. PNET usually seen on Diff-Quik stain. Homer-Wright rosettes are
occurs in children under 10 years old. PNET shares a unique seen in some cases, but neuropil and ganglion cells
247
(A) (C)
(B) (D)
Figure 12.17 Primitive neuroectoderm tumor. (A). Small blue neoplastic cells with rosette-like groupings. Diff-Quik, 100×. (B). Small blue cells
without nuclear streaking or molding Papanicolaou, 100×. (C). Close-up of rosette shows hyperchromatic uniform oval nuclei Papanicolaou, 400×. (D).
Histology of PNET showing small uniform round cells forming vague rosettes. H&E, 100×.
are absent. The differential diagnosis includes other Histologic features

small round cell tumors such as neuroblastoma, lym- PNET are characterized by uniform small round cells with
phoma, and rhabdomyosarcoma. However, PNET lacks round nuclei containing fine chromatin, scanty clear or
the fibrillary background of neuroblastoma and lacks eosinophilic cytoplasm, and indistinct cytoplasmic mem-
the lymphoglandular bodies of lymphoma on Diff-Quik branes. Mitotic figures are common, as are necrosis and
stain. In addition to clinical features (age, primary site, endothelial hyperplasia. A further aid in the differential
catecholamine levels), immunohistochemistry and cyto- diagnosis is provided by the presence of Homer-Wright
genetic study are needed in difficult cases in establish- rosettes in PNET (Fig. 12.17D).
ing the correct diagnosis.
Key cytomorphologic features: primitive CD99 is expressed in up to 97% of PNETs. The EWS/PNET
neuroectodermal tumors spectrum shows immunohistochemical evidence of neuro-
* Cellular smears of discohesive monotonous, small, ectodermal differentiation by positivity for antigens such as
round to oval cells with very high N/C ratios NSE, PGP 9.5, neurofilament, Leu-7, and synaptophysin. A
* Clustering and Homer-Wright rosettes are seen in some positivity of these markers is more commonly seen in PNET.
cases Neurofilament expression appears to be a more specific
* Absence of nuclear molding or streaking, lymphogland- marker, but its frequency is generally low in this family of
ular bodies, and neuropil tumors. Fluorescence in situ hybridization analysis using a
248
DNA probe for the Ewing sarcoma breakpoint region 1 1. Well-differentiated cell type. Tumor cells occur singly,
(EWSR1) on chromosome 22g12 can detect a rearrange- in loose groupings, and in cohesive groupings
ment of the EWSR1 locus and confirms the diagnosis. (Fig. 12.18A–C). They have elongated or cigar-shaped
Ultrastructurally, neurosecretory granules and neurite-like nuclei with blunt ends and have either little recogniz-
cytoplasmic processes are present. able cytoplasm or small amounts of well-defined cyto-
plasm. The elongated nuclei are often in parallel or
polar arrangements.
Soft tissue tumors 2. Anaplastic cell type (Fig 12.19A–C). Tumor cells lie
Virtually any mesenchymal neoplasm can arise in the soft singly. They are spindle-shaped cells with tapered
tissue of the mediastinum despite their rarity. Lipomatous cytoplasm and ovoid, elongated, or irregularly shaped
tumors, solitary fibrous tumor, synovial sarcoma, and nuclei with variation in size and coarse clumping of
angiosarcoma have been thoroughly discussed in chromatin. Many multinucleated tumor cells are usu-
Chapter 11. To avoid redundancy, this chapter will only ally present. The cytoplasm of mononuclear tumor
discuss the rare mediastinal leiomyosarcoma, chondrosar- cells is scanty and poorly defined, whereas the multi-
coma, and chordoma. nucleated tumor cells have moderate amounts of well-
defined cytoplasm.
Leiomyosarcoma
Clinical features
Key cytomorphologic features: leiomyosarcomas
Smooth muscle tumors presenting as mediastinal soft tissue
* Variable cytologic features, ranging from well-differentiated
masses are extremely rare and often are mistaken for other
to spindled, round cell, and pleomorphic cell type.
neoplastic conditions. Leiomyosarcomas may arise as pri-
* Most commonly, elongated or cigar-shaped nuclei with
mary tumors in both anterior and posterior compartments.
blunt ends in parallel or polar arrangments.
In a study of ten cases, three cases were located in the
anterior mediastinum and seven in the posterior mediasti-
Histologic features
num. The patients’ ages ranged from 26 to 71 years (mean,
56 years); three were women, and seven were men. The Mediastinal leiomyosarcomas, similar to the lesions at other
patients with anterior mediastinal tumors all presented anatomic sites, are composed of the palisading spindle cells
with signs and symptoms referable to their lesions; the with cigar-shaped, blunt-ended nuclei, arranged in fascicular
patients with posterior mediastinal masses (with the excep- growth pattern. A histologic spectrum is present, ranging
tion of one) were asymptomatic. The tumors in all patients from low-grade tumors (Fig. 12.18D) with mild-to-moderate
appeared to arise from the soft tissues within the mediasti- nuclear atypia and low mitotic activity to high-grade tumors
num and were unrelated to adjacent structures. All patients (Fig. 12.19D) with marked nuclear pleomorphism, extensive
were treated with surgical excision. On follow-up, three areas of necrosis, and high mitotic activity. One case reported
patients with Stage IIIb and IVa tumors died 2–7 years by Moran et al was characterized by a striking epithelioid
after surgery, and two patients with Stage Ib and IIb were morphology with large, round cells arranged in small clusters;
alive and well 4 and 6 years after surgery, respectively. another was associated with an incidental microscopic focus
of thymic seminoma in the adjacent thymus.
Mediastinal leiomyosarcomas were well circumscribed on Ancillary techniques
chest CT scan, ranging from 6 to 18 cm, containing cystic Immunohistochemical stains showed positive labeling of the
and myxoid areas. Because of their posterior mediastinal tumor cells with smooth muscle actin, desmin, and vimentin
location, large size, and frequent areas of cystic and myxoid antibodies, and negative for c-Kit.
degeneration, they may be confused radiologically with neu-
ral tumors. Chondrosarcoma
Clinical features
Cytologic features Chondrosarcoma of the mediastinum is extremely rare.
Leiomyosarcoma can be classified into two types on aspira- Suster and Moran reported six cases of primary chondro-
tion smears: sarcoma presenting as extraskeletal soft tissue masses in the
249
(A) (C)
(B) (D)
Figure 12.18 Leiomyosarcoma, well-differentiated type. (A). Cohesive fragments of spindle cells in metachromatic matrix. Diff-Quik, 400×.
(B). Fascicles of spindle cells. Papanicolaou, 40×. (C). Fascicles of spindle cells. Papanicolaou, 100×. Inset: Desmin immunoreactivity. (D). Histology of
leiomyosarcoma showing fascicles of spindle cells with tapered cytoplasm. H&E, 400×.
posterior mediastinum. The patients were five women and mediastinum without radiographic evidence of origin from
one man aged 11 to 63 years (median, 31 years). All of the bone. Due to their relatively small size, good circumscrip-
lesions were treated by complete surgical excision, followed tion, focal areas of calcification, and posterior mediastinal
in two cases by post-operative radiation therapy. Clinical location, the pre-operative clinical diagnoses included
follow-up was available in five cases: two patients with benign neurogenic tumor.
mesenchymal chondrosarcoma presented with local recur-
rence after 3 and 7 years, one developed metastases to the Cytologic features
sacrum 8 years after initial diagnosis and died, and one was Aspirates obtained from mediastinal chondrosarcoma are
alive and well without evidence of disease after 6 years. characterized by strickingly metachromatic myxoid stroma
The patient with myxoid chondrosarcoma of the posterior (Fig. 12.20A–C) to hyaline cartilage studded with chondro-
mediastinum developed bilateral pulmonary metastases cytes with marked atypical nuclei (Fig. 12.21A–C). If most
10 months after surgery. These tumors can show a propen- are mesenchymal chondrosarcomas, then smears are domi-
sity for local aggressive behavior with high recurrence rate nated by small round cells with solitary hyperchromatic
and a definite potential for distant metastases. nuclei and high N/C ratios: at times one may also find
islands of well-formed hyaline cartilage. Myxoid tumors
Radiographic features are composed of fragments of myxoid matrix containing
Chondrosarcoma presented as well-circumscribed tumor even smaller and blander cells. Well-formed capillaries are
masses centered in the soft tissues in the posterior absent.
250
(A) (C)
(B) (D)
Figure 12.19 Leiomyosarcoma, anaplastic cell type. (A). Dyscohesive cells separated from a metachromatic vascular network. Diff-Quik,100×. (B). A
small loose cluster of spindle cells. Papanicolaou, 400×. (C). A binucleated anaplastic cell with nuclear grooves. Papanicolaou, 1000×. (D). Histology
showing hypercellular spindle cell tumor. Resected tumor. H&E, 100×.
Key cytomorphologic features: chondrosarcoma immunohistochemical and cytogenetic results very similar
* Metachromatic myxoid stroma to rigid hyaline cartilage to Ewing sarcoma.
* Increased nuclear density
* Nuclear atypia Chordoma
Clinical features
Histologic features Mediastinal chordoma is extremely rare. Six primary poste-
Mediastinal chondrosarcomas show a spectrum of features rior mediastinal chordomas were reported by Suster and
that range from extraskeletal myxoid chondrosarcoma Moran: three patients were female and three were male
(Fig. 12.20D) to mesenchymal chondrosarcoma between the ages of 8 and 65 years (mean 40.6 years). On
(Fig. 12.21D), to moderately well to poorly differentiated clinical follow-up, two patients died with metastases to the
chondrosarcoma. lungs, chest wall, and liver from 1 to 3 years after diagnosis,
and two patients are alive and well without evidence of
Ancillary techniques disease after 3 and 16 years. Chordomas are malignant
Immunohistochemistry is helpful in the specific diagnosis tumors arising from the remnants of the fetal notochord,
of chondrosarcomas, which are positive for S-100, but which is situated within the vertebral bodies and intraverte-
negative for cytokeratin, which is used to exclude bral discs. These tumors grow slowly. They occur at all ages,
chordoma. Mesechymal chondrosarcoma may show but are more frequent in the fifth and sixth decades of life.
251
(A) (C)
(B) (D)
Figure 12.20 Chondrosarcoma, myxoid type. (A). Metachromatic myxoid substance studded with chondrocytes. Diff-Quik, 100×. (B). Chondrocyte
surrounded by radiating fibrillary metachromatic matrix. Diff-Quik, 400×. (C). The matrix is inconspicuous in Papanicolaou (100×). (D). Histology of
myxoid chondrosarcoma showing strands of chondroblasts in myxoid background. Resected tumor. H&E, 100×.
Fifty percent of cases arise in the sacrococcygeal area, with right), and others are small with small amounts of non-
the remaining cases along the vertebral spine and in the vacuolated cytoplasm (Fig. 12.22A,B, left). Some tumor
sphenooccipital area. cells are binucleated, but multinucleated cells are uncom-
mon. Their nuclei are often hyperchromatic.
In all cases in the series, the tumors presented radiograph- Key cytomorphologic features: chordoma
ically as relatively well-circumscribed, encapsulated soft tis- * Solitary or loose groupings of physaliferous cells
sue masses that did not relate to the thoracic or dorsal spine. * Metachromatic mucoid background
In only one case, focal infiltration of bone at the level of
T6-T7 was observed at the time of surgery. Histologic features
Mediastinal chordomas showed a spectrum of histologic
Cytologic features features that ranged from sheets and cords of physaliferous
Chordomas are gelatinous and soft to the needle, thus aspi- cells (Fig. 12.22C) with abundant vacuolated cytoplasm to
ration smears are characterized by a strikingly metachro- small, stellate cells embedded within an abundant mucoid
matic mucoid background in Diff-Quik stain (Fig. 12.22A). matrix. In one case, the cell population showed more pro-
Relatively scanty solitary neoplastic cells and neoplastic cell nounced nuclear atypia with loss of cytoplasmic vacuoliza-
loose groupings are seen in smears. The tumor cells exhibit a tion, frequent mitotic figures, necrosis, and solid areas
variable cytology. Some tumor cells are classic physaliferous characterized by a perivascular distribution of atypical spin-
cells with abundant vacuolated cytoplasm (Fig. 12.22A,B, dle cells set against a myxoid stroma. Another case showed
252
(A) (C)
(B) (D)
Figure 12.21 Chondrosarcoma. (A). Fragments of firm metachromatic cartilage. Diff-Quik, 100×. (B). Hyaline cartilage with patches of increased
nuclear density. Papanicolaou, 100×. (C). Close-up of the nuclei show nuclear enlargement, irregular contour, and hyperchromasia. Papanicolaou,
400×. (D). Histology of chondrosarcoma showed hyaline cartilage with lacunae containing chondroblasts with marked atypical nucleus (inset).
Resected tumor. H&E, 100×.
features of chondroid chordoma, with an immature resected 6 years ago with recurrence at surgery site 2 years
chondroid-appearing matrix surrounding the atypical later. CT-guided FNA of of left lower lobe lung nodule
tumor cells. showed bland spindle cells (Fig. 12-23A,B). A week later
FNA of a 1 cm right lower lobe nodule was performed. This
Ancillary techniques time, the senior author did the on-site assessment and made
a single smear and put most of the aspirate into CytoRich
Chordoma cells coexpress S-100 and cytokeratins. The cyto-
Red and a cell block was made (Fig. 12.23C). Cell block
keratin immunoreactivity (Fig. 12.22D) is important to
shows spindle cell sarcoma, which is positive for bcl-2 and
exclude chondrosarcoma, which may appear similar to
negative for all other spindle cell markers. Comparison with
chordoma on smears with metachromatic matrix and even
original tumor (Fig. 12.23D) shows identical histology and
pseudo-physaliferous appearing cells. Chordomas are also
immunoprofile. The take home message of this case is that
positive for EMA and vimentin.
many cancer cells do not fulfill traditional cytologic critieria
of malignancy. In such cases, histology via cell block and
CLINICAL VIGNETTES immunostains are essential for definitive diagnosis.
Case 1 Case 2
A 73-year-old woman presented with bilateral lung nodules. A 75-year-old man with history of metastatic melanoma to
History of solitary fibrous tumor of posterior mediastinum chest wall, presented with destructive thoracic vertebral
253
(A) (C)
(B) (D)
Figure 12.22 Chordoma. (A). Metachromatic mucoid background substance containing non-vacuolated tumor cells on the left and physaliforous
cellson the right. Diff-Quik, 400×. (B). Non-vacuolated tumor cells on the left and physaliforous cells on the right. Papanicolaou, 400×. (C). Histology of
chordoma with physaliforous cells. H&E, 400×. (D). Cytokeratin immunostain on resected chordoma, 100×.
mass. CT-guided FNA yielded fascicles of spindle cells in a Duwe BV, Sterman DH, Musani AI. Tumors of the mediastinum. Chest
fibrillary extracellular matrix (Fig. 12.24). Immunostain on 2005; 128: 2893–2909.
cell block showed negativity to HMB45 and positivity for

S-100 and vimentin. The case was signed out by the senior
Neurogenic tumors of the mediastinum
author in 1996 as malignant peripheral nerve sheath tumor.
One year later, HMB45 negative spindle cell melanoma was Reeder LB. Neurogenic tumors of the mediastinum. Semin Thorac
reported, and 4 years later, a series of 16 cases of metastatic Cardiovasc Surg 2000; 12: 261–267.
spindle cell melanoma resembling malignant peripheral

nerve sheath tumor was reported, and now it is common
Radiology
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Bastos P, Magalhaes A, Fernandes G, et al. Primary cysts and tumors of Weiss SW & Goldblum JR. Enzinger and Weiss’s soft tissue tumors, 4th
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(A) (C)
(B) (D)
Figure 12.23 Malignant solitary fibrous tumor, recurred as lung metastasis. (A). Cohesive fragment of tumor with some single cells scattered along
the periphery. Diff-Quik, 100×. (B). Small uniform spindle cells associated with metachromatic stroma. Nuclei <2× RBC. Diff-Quik, 400×. Inset:
Deceptively bland nuclei. Papanicolaou, 400×. (C). Spindle cells without nuclear atypia. Cell block. H&E, 400×.Inset: positive bcl-2 immunostain on cell
block. (D). Original tumor showing cell-rich area and cell-poor area with vascular network. H&E, 100×.
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Middle and posterior mediastinum

Chapter · May 2012

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12 MIDDLE AND POSTERIOR MEDIASTINUM

hong q. peng, m.d. and grace c. h. yang, m.d.

INTRODUCTION Radiologic studies for mediastinal mass lesions

LUNG AND MEDIASTINUM CYTOHISTOLOGY

surgery, cases of acute mediastinitis usually arose from

MIDDLE AND POSTERIOR MEDIASTINUM

Table 12.1 Diagnostic modalities of middle/posterior mediastinal lesions

combination of the clinical and radiologic studies and

LUNG AND MEDIASTINUM CYTOHISTOLOGY

Radiographic features Cytologic features

MIDDLE AND POSTERIOR MEDIASTINUM

(A) (B) (C)

(D) (E) (F)

transformation can occur. Plain chest radiographs can Histologic features

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

Histologic features Granular cell tumor

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

Cytologic features Histologic features

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

Neuroblastoma Key cytomorphologic features: neuroblastoma

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

are absent. The diﬀerential diagnosis includes other Histologic features

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

cell block showed negativity to HMB45 and positivity for

spindle cell melanoma resembling malignant peripheral

Primary mediastinum cysts and tumors Histology

MIDDLE AND POSTERIOR MEDIASTINUM

LUNG AND MEDIASTINUM CYTOHISTOLOGY

MIDDLE AND POSTERIOR MEDIASTINUM

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