Diagnostic Cytology
Fig. 26.17 Various tumor cell types seen in anaplastic large-cell lymphoma. (A, C, and F) ‘Hallmark" cells with kidney- or embryo-like nuclei. (B) Nondescript
small round cell. (D and E) ‘Doughnut" cells. (G) ‘Plasmacytoid" cell. (H) ‘Hand mirror" cell (seen in air-dried smears only). (I) Multinucleated cell with wreath-like
arrangement of nuclei. (J) Cell with multilobulated nucleus.
CD5-positive if thymic origin); Hodgkin's lymphoma
(CD30-positive, CD15-positive, and CD20 focally and
weakly positive); anaplastic large-cell lymphoma
(CD20-negative, CD30-positive, T-cell markers often
positive, epithelial membrane antigen sometimes positive,
and ALK protein sometimes positive); metastatic malignant
melanoma (S-100 protein-positive and
Anaplastic Large-Cell Lymphoma
Anaplastic large-cell lymphoma sometimes occurs in the medi-
astinum of children and young adults.47 Cytologic examina-
tion, when coupled with immunocytochemistry, can provide a
definitive diagnosis for this rare type of high-grade lymphoma
(Fig. 26.17).102
lymphoma, common variant, shows widely dispersed large
"hallmark" cells that contain eccentric "kidney-shaped" or
"embryo-like" nuclei, several prominent "rod-shaped" or angu-
lated basophilic nucleoli, and abundant amphophilic cytoplasm.
"Doughnut" cells, tumor cells with multilobated nuclei, and
multinucleated giant cells with a "wreath-like" arrangement of
nuclei are occasionally found. A small number of "plasmacytoid"
tumor cells, nondescript small round tumor cells, and reactive
polymorphs are also present. In contrast, "plasmacytoid" cells
and nondescript small to medium-sized tumor cells represent the
predominant cell population in anaplastic large-cell lymphoma,
small-cell variant. The "plasmacytoid" appearance is further exag-
gerated in air-dried smears. In air-dried smears, small intracyto-
plasmic vacuoles and scanty azurophilic granules are also noted.
Immunocytochemical study performed on cell block sec-
tions demonstrates membranous and paranuclear "dot-like"
positivity for CD30. Cytotoxic markers (e.g. granzyme B and
TIA-1) are also positive. Staining for epithelial membrane
antigen, leukocyte common antigen, T-cell markers (e.g. CD3
and CD45RO), and ALK protein is variable.
Anaplastic lymphoma kinase protein overexpression is help-
ful in the prognostic subcategorization of anaplastic large-cell
lymphoma. As for lymphoma in general, immunopositivity
for ALK protein is almost never demonstrated in nonanaplas-
tic large-cell lymphoma cases, with rare exceptions in a pecu-
liar subgroup of diffuse large B-cell lymphoma. Among the
group of anaplastic large-cell lymphoma, ALK protein-positive
tumors often occur in younger age groups, have a male predi-
lection, and tend to carry a more favorable clinical outcome,
while the ALK protein negativity is associated with poor progno-
sis. Immunostaining for ALK protein can also correlate with the
underlying molecular genetics. Lymphoma cells with t(2;5) tend
to show a mixed cytoplasmic, nuclear, and nucleolar staining
pattern, due to the production of a nucleophosmin (NPM)-ALK
chimeric protein. NPM provides nuclear localization signals for
this NPM-ALK fusion gene product, explaining the additional
nuclear and nucleolar staining of ALK protein. In contrast, lym-
phoma cases with translocation lacking the involvement of NPM
gene, such as t(1;2), show a pure cytoplasmic staining pattern.
Cytologic differential diagnosis of anaplastic large-cell lym-
phoma includes seminoma, poorly differentiated non-small-cell
carcinomas (thymic or nonthymic), and diffuse large B-cell lym-
phoma. The tumor cells in seminoma often lack the marked
nuclear membrane irregularities seen in anaplastic large-cell lym-
phoma cells. Immunocytochemistry is helpful in the distinction.
Key features of anaplastic large-cell lymphoma
• Low-power cytology: heterogeneous population of atypi-
cal lymphoid cells and polymorphs.
• High-power cytology: widely dispersed atypical lymphoid
cells of various morphology, including "hallmark" cells,
"plasmacytoid" cells, and nondescript small round cells.
• Cell block sections: heterogeneous population of atypical
lymphoid cells.
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