small round cells associated with fibrillary matrix, represent-
ing neuroectodermal component. Sometimes these immature
neuroectodermal cells may predominate, resulting in a cyto-
logic picture mimicking neuroblastoma. While the teratoma-
tous architecture is better appreciated in cell block sections,
the role of immunocytochemistry is limited (except in defining
the nature of immature component or excluding other germ
cell or somatic malignancies). In fine-needle aspirates of ter-
atoma with malignant transformation, both malignant and
benign cells, mainly of epithelial nature, are seen. Commonest
malignant components include squamous cell carcinoma and
Cytologic differential diagnosis, especially for mature ter-
atoma with prominent cystic changes, includes bronchogenic
cyst. The neoplastic element may also be masked by the florid
granulomatous and inflammatory reaction present in some
cases. The abundance of mature squamous cells in mature ter-
atoma may be mistaken as well-differentiated squamous cell
carcinoma. The latter, however, often shows more cellular dis-
persion and subtle but yet discernible cytologic atypia. It is also
prudent to rule out the possibility of mixed germ cell tumor
with teratomatous component, especially if there is an imma-
ture element present.
Key features of teratoma
• Low-power cytology: admixture of epithelial and mesen-
• High-power cytology: bland-looking epithelial and stro-
mal cells, with or without loose aggregates of immature
small round cells.
• Cell block sections: haphazard admixture of somatic
tissues better appreciated.
• Immunocytochemistry: usually not necessary.
• Cytologic differential diagnosis: non-neoplastic lesions
(such as bronchogenic cyst).
Precursor T-lymphoblastic Lymphoma
Precursor T-lymphoblastic lymphoma usually occurs in late
childhood and adolescence, with male predominance.47 It typi-
cally involves thymus and mediastinal lymph nodes and may
present with symptoms of tracheal compression and superior
vena cava obstruction. Associated pleural and pericardial effu-
sions are common.
Fine-needle aspiration can be adequate for accurate diagnosis
of precursor T-lymphoblastic lymphoma.5,39,92-94 The cytologic
preparations are hypercellular and composed of a monotonous
population of dyscohesive small to medium-sized lymphoid
cells with high nuclear-to-cytoplasmic ratio (Fig.
The lymphoid cells are 1.5-2 times larger than small lymphocytes.
They contain hyperchromatic round nuclei, condensed or finely
dispersed chromatin, indistinct-to-small nucleoli, and scanty
cytoplasm (Fig. 26.15B). Mitotic figures are commonly seen.
Tingible-body macrophages and lymphoglandular bodies are
present in the background. Although occasional cases with
convoluted nuclei may be found, nuclear membrane irregu-
larities are usually not obvious and nuclear pleomorphism is
often minimal. Azurophilic granules may be identified in air-
dried smears. Nondescript large cells (which may represent
cortical epithelial cells in thymoma and centroblasts in reac-
tive lymphoid hyperplasia or follicular lymphoma) are absent,
and multinucleated tumor giant cells are almost never found.
In poorly preserved smears, the lymphoma cells may be mis-
taken as small lymphocytes, resulting in false-negative cytologic
Immunocytochemical study (Fig. 26.15C) shows that these
lymphoid cells are positive for TdT. T-cell markers (includ-
ing CD3 and CD5) and CD1a are variably expressed. Neither
immunocytochemistry nor flow cytometry can demonstrate
monoclonality. It is noteworthy that the immunophenotype of
precursor T-lymphoblastic lymphoma and that of normal pre-
cursor T cells in thymoma can be identical, which may pose an
important diagnostic pitfall.59 Demonstration of clonality by
molecular studies is helpful in confirming the malignant nature
of the lymphoid cells. Sometimes, both T-beta receptor and
immunoglobulin gene rearrangements are demonstrated, sug-
gesting the biphenotypic nature of certain examples of precursor
Other cytologic differential diagnosis in this age group
includes neuroblastoma and rhabdomyosarcoma. The former
often occurs in posterior mediastinum and possesses various
amounts of fibrillary matrix in the background. The diagnosis
can be confirmed with immunoreactivity for neuronal markers.
On the other hand, fine-needle aspirates of rhabdomyosarcoma
contain occasional differentiating rhabdomyoblasts, with cyto-
plasmic striations and distinct nucleoli. Immunocytochemistry
also helps to demonstrate the myogenic nature of the tumor
Key features of precursor T-lymphoblastic lymphoma
• Low-power cytology: a sea of small lymphoid cells.
• High-power cytology: monotonous population of widely
dispersed and mitotically active small lymphoid cells,
sometimes with nuclear convolutions; no admixture of
large atypical cells; lymphoglandular bodies in the back-
• Cell block sections: monotonous population of small
• Immunocytochemistry: TdT-positive, T-cell markers vari-
ably positive, and cytokeratin-negative.
• Cytologic differential diagnosis: type B1 or B2 thymoma
(cytokeratin-positive cells present); reactive lymphoid
hyperplasia (TdT-negative); low-grade non-Hodgkin's
lymphoma, such as thymic extranodal marginal zone B-
cell lymphoma (TdT-negative); neuroblastoma (neuronal
markers positive); rhabdomyosarcoma (desmin-positive
and myogenin-positive); small-cell carcinoma (cytokera-
tin-positive, neuroendocrine markers positive, and TTF-
Primary Mediastinal Large B-cell Lymphoma
Primary mediastinal large B-cell lymphoma (synonym: medias-
tinal large-cell lymphoma of B type with sclerosis) is a subtype
of diffuse large B-cell lymphoma of putative thymic B-cell ori-
gin, commonly associated with stromal fibrosis (Fig. 26.16A).47
It accounts for 2-3% of all cases of non-Hodgkin's lymphoma
and affects mainly young adults in the third and fourth decades,
with slight female predilection. The disease involves anterosu-
perior region of mediastinum and is not associated with superfi-
cial lymphadenopathy or hepatosplenomegaly at presentation.
Superior vena cava syndrome is common. The prognosis of this
lymphoma is similar to that of other localized diffuse large
B-cell lymphoma. Diffuse large B-cell lymphoma occurring