The mediastinum is a site for the development of epithelial, mesenchymal,
lymphoproliferative, neurogenic, & germ cell neoplasms. Utilization of fine needle aspiration biopsy
(FNAB) for the diagnosis of mediastinal tumours is much less than for other body sites. A study
comparing the efficacy of mediastinal FNAB & core needle biopsy showed both methods performed with an
overall diagnostic accuracy of 100%, however the ability of FNAB to subtype lesions was less than tissue
biopsy. FNA is increasingly being used to sample mediastinal masses by combining it with endoscopy and
ultrasound. Some centers using endoscopic ultrasound-guided FNA also combine it with core
needle biopsy so that both conventional cytologic smears & tissue sections can be simultaneously
Because of the broad spectrum of tissue types in this region, and the variety of cell
morphology even within the same neoplasm, adequate sampling cannot be overemphasized; close communication
with the interventional radiologist or endoscopist is mandatory.
I. EPITHELIAL TUMORS
Thymoma arises in the antero-superior mediastinum, is a neoplasm of older adults, and
occurs in up to 40% with a paraneoplastic syndrome. The cytologic diagnosis is demanding. Smears vary
depending on the area sampled, what cell type (epithelial or lymphoid) is most common, whether spindle
cell foci are present, and whether fluid has been aspirated.
- moderately cellular smears with a mixture of lymphocytes and epithelial cells.
- epithelial cells in tightly clustered microfragments, some as loose clusters, and some as
single cells. Cells are isomorphic, polygonal or spindle shaped with round to oval smooth nuclear
borders, indistinct nucleoli, and finely dispersed chromatin.
- lymphocytes are primarily small mature forms
- thymomas with spindle morphology have a fusiform configuration
Many of the histologic features of thymoma, e.g. perivascular
spaces, cystic transformation, organotypical architecture, and lobule formation cannot be recognized in
smears. Certainly any attempt to distinguish an invasive from a non-invasive thymoma is impossible using
FNAB since the cell morphology is identical to both, and smears cannot evaluate capsular invasion in any
Immunophenotyping on smears or cell block is helpful to
recognize the epithelial cells. Prudence dictates that cytokeratin (CK) staining of a smear should be
performed whenever possible if thymoma is suspected. These CK+ cells are randomly scattered as single
cells or small cell groups within the lymphoid population whereas entrapped thymic epithelium in a
lymphoma consists of an irregular branching network.
B. Thymic Carcinoma
Primary carcinomas of the thymus are rare lesions. The vast majority are actually derived
from the lung. Histologic variants of thymic carcinoma include keratinizing squamous cell carcinoma,
sarcomatoid carcinoma, neuroendocrine carcinoma, mucoepidermoid carcinoma, and undifferentiated
(lymphoepithelioma-like) carcinoma. No substantial series exists. The cytopathology is similar to that
seen in lung aspirates.
II. LYMPHOPROLIFERATIVE DISORDERS
A. Hodgkin Lymphoma
Hodgkin lymphoma (HL) is the most common mediastinal lymphoma. There is a predilection
for women with a peak in the 2nd - 4th decade. In Caucasians, HL comprises up to
35% of all lymphomas in contrast to only 5-10% in Orientals.
- heterogeneous lymphocyte background
- key feature is identification and recognition of randomly dispersed Reed-Sternberg (R-S) cells.
These are large cells with mirror-image binucleation, or mononuclear variants greater than 20 μm.
diameter, with smooth, bosselated, or distinctly multilobated nuclei.
- nucleoli as large as a red cell in most cases, and often misshapen
- cytoplasm is moderate to sometimes abundant, and pale staining.
Sclerotic bands, and lacunar cells per se cannot be appreciated.
Cytologic Mimics of Reed-Sternberg Cells
- Dendritic Cells
- Pleomorphic Sarcoma
- Large Cell Lymphoma
- Large Cell Carcinoma
Flow cytometry plays no role in the immunophenotyping of HL due to its non-diagnostic
results. R-S cells are CD15/CD30 positive, and CD45/CD20/epithelial membrane antigen (EMA) negative in
classic HL, while the Lymphocyte Predominant form shows CD15/CD30 negative, and CD45/CD20/EMA positive
B. Large Cell Lymphoma
Large cell non-Hodgkin lymphoma (NHL) of the mediastinum can be a primary tumor arising in
the thymus, or a lymphoma secondarily involving lymph nodes in this region.
B1. Primary mediastinal (thymic) Large B-cell Lymphoma:
Accounts for 2-3% of all NHL with a putative origin from thymic B-cells. Demographics include young
adults (avg. 37 y.), and a female predominance (2:1). Patients present with superior mediastinal
syndrome (dyspnea, tracheal compression, SVC obstruction).
- smears may be hypocellular. Large lymphocytes are in a predominantly non-cohesive distribution
(so-called single cell pattern); lymphoglandular bodies present.
- round to oval nuclei with smooth or irregular borders, visible nucleoli, intensely basophilic
- connective tissue microfragments may distort lymphocytes making them spindled shaped and thus
confused for a sarcoma. Flow cytometry shows CD45, CD19, CD20 positive.
B2. Anaplastic Large Cell Lymphoma (ALCL) is a T-cell
lymphoma that may occur in the mediastinum. Children and young adults are principally affected.
- moderate to high cellularity with large malignant cells having multinucleated forms, pleomorphic
shapes, intranuclear inclusions, concentric nuclear "donut" shapes, and nuclear notches are all possible.
Large misshapen nucleoli are common
- cytoplasm is abundant; may have coarse or fine vacuolation. Flow cytometry shows CD2, CD30, CD4 +
while CD5, CD7 are frequently negative.
C. Lymphoblastic Lymphoma (LL)
One of the three most common NHL of children. Experience has shown that FNAB is
an excellent method for the diagnosis of LL. This aggressive neoplasm comprises 1/3rd to ½ of
pediatric lymphomas. The peak incidence is in adolescent and young adult males.
An anterior mediastinal mass occurs in up to 80% of patients is often massive, and may induce a
superior vena cava syndrome.
- hypercellular single cell pattern of monotonous lymphoblasts 1.5-2 x > small lymphocytes.
- finely dispersed chromatin, small or imperceptible nucleoli, smooth or irregular (convoluted)
nuclear rims, and an extremely meager amount of cytoplasm.
- mitotic figures, tingible body macrophages, and lymphoglandular bodies are variable
About 80% are T-cell and stain for these markers, while the remaining are B-cell. Nearly all are
positive with terminal deoxynucleotidyl transferase (Tdt). It should be remembered that thymic
lymphocytes are normally also Tdt positive, and immunophenotypically identical to T-lymphoblasts.
III. GERM CELL TUMORS
Mature teratoma is the most common form of mediastinal germ cell tumor (GCT).
Germinoma/seminoma is the 2nd most frequent type. Men in the 2nd -
4th decade are affected. These may be discovered as incidental lesions on chest X-ray, but
large masses are symptomatic. The possibility of a metastasis always needs to be excluded.
- cells in small loose clusters or singly. Large cells have rounded to polygonal shape, round or oval
nuclei with coarse chromatin, and a single large nucleolus. Many bare nuclei.
- moderate amount of cytoplasm; often contains coarse sharply demarcated glycogen-filled vacuoles in a
"bleb or blister-like" fashion.
- detached cytoplasmic contents distributed in a lacy linear configuration producing a so-called
"tigroid" pattern. Smears may contain lymphoglandular bodies.
Germinomas: CK negative, and PLAP+, and focal staining with CD30.
B. Non-Seminomatous Germ Cell Tumors
The major subtypes in this category include yolk-sac tumor, embryonal carcinoma, and
choriocarcinoma. Clinical features are similar to those for seminomatous GCT.
- large cytologically malignant cells with nucleo- and nucleolomegaly.
- variable vacuolated cytoplasm, & background necrosis
- cells loosely or tightly aggregated into 3-dimensional groups; may display papillary or glandular
features. Hyaline globules are unusual.
Immunophenotypically, express AFP & focal staining for b-HCG, CD30.
IV. NEURAL TUMORS
The vast majority of posterior mediastinal neoplasms are neurogenic.
Neurogenic tumors account for ≈ 20-30% of mediastinal neoplasms. Schwannoma is the
most common mediastinal neural tumor. Patients are usually 20-40 yrs.
- spindle cells in loose clusters and single forms often but not invariable distinctive irregular
nuclear outline described as "buckled", "wavy", or "fish-hook".
- homogeneous bland chromatin; cytoplasm pale, in thin strands; cell borders typically indistinct.
Metachromatic stroma is variable.
Older female children and young adults are affected. Most are
- hypocellular smears; microfragments on occasion. Isomorphic spindle cells mixed with ganglion cells
which have voluminous cytoplasm; 1 or more nuclei & a centrally placed nucleolus.
The most common childhood tumor in that site.
- highly cellular smears of uniform, round to polygonal small cells in clusters, acinar structures (Homer-Wright rosettes) with fibrillary matrix (neuropil).
- nuclei: single, hyperchromatic, diffuse even chromatin, small nucleoli; binucleation
- cytoplasm: scanty in solitary cells; wispy cell processes; more apparent in aggregates; increased volume in maturing neuroblasts and ganglion cells
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