1 February 2006 – Case of the Week #36
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We thank Dr. Adrian A. Suarez, National Children’s Hospital, San Jose, Costa Rica, for contributing this case. We invite you to contribute a Case of the Week by sending an email to NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting. We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US) for your time after we send out the case. Please only send cases with a definitive diagnosis.
Case of the Week #36
The patient was a seven year old girl with a three month history of a mass in the right side of her chest. On physical examination the lesion was mildly tender and measured about 3 cm. A CT scan showed a large tumor involving soft tissues and extending from the subcutaneous fat into the anterior mediastinum (image). As is usual in our institution, a fine needle aspiration biopsy was performed.
Fine needle aspiration biopsy:
Air dried smears, stained with May-Grünwald-Giemsa, were highly cellular. Cells were non-cohesive and ranged from small to very large (FNA image#1, image#2, image#3). Nuclei were pleomorphic, including many multilobulated or convoluted forms, and some were doughnut or wreath shaped. The cells had variable amounts of blue cytoplasm, and many of the larger ones showed eccentric clear-pink areas. There were frequent mitotic figures. Lymphoglandular bodies were scarce.
Immunocytochemistry, performed on alcohol fixed material, demonstrated strong nuclear and cytoplasmic reactivity for ALK-1 (image), membrane reactivity for CD45 and weak cytoplasmic reactivity for CD30.
Flow cytometric analysis, performed in a saline cell suspension, showed a neoplastic lymphoid population with partial CD4 and CD8 co-expression (flow cytometry - forward scatter vs. side scatter, CD4 vs. CD3, CD4 vs. CD8). No expression of CD3 was detected.
What is your diagnosis?
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Anaplastic large cell lymphoma
Anaplastic large cell lymphoma (ALCL) causes 10-15% of childhood non-Hodgkin lymphomas versus 3% in adults. T-cell origin and T-cell lineage can usually be proven by molecular studies, even if no T-cell antigen expression is present by immunohistochemistry. Nodal involvement is common.
In lymph nodes, there is infiltration of interfollicular T cell zones and nodal sinuses. Tumor cells are anaplastic and large, and may resemble Reed-Sternberg cells, with abundant cytoplasm and either horseshoe, wreath-like or multiple nuclei. Tumor cells also have multiple nucleoli and a perinuclear eosinophilic region. There is brisk mitotic activity, and frequent vascular wall invasion, particularly in extranodal cases.
Fine needle aspiration cytology smears show dissociated cells with abundant, lightly basophilic, vacuolated cytoplasm; oval, round or lobulated nuclei; and binucleate, trinucleate and multinucleate cells with a wreath-like arrangement of nuclei and prominent nucleoli (Acta Cytol 1997;41:1253, Acta Cytol 1996;40:779, Diagn Cytopathol 1996;14:155)
Immunohistochemistry is necessary to confirm the diagnosis of anaplastic large cell lymphoma. Tumor cells have characteristic surface membrane and cytoplasmic paranuclear dot-like staining for CD30. They are also often immunoreactive for CD2, CD4 and CD25, with variable staining for CD43 and EMA, and occasional staining for B cell markers.
Anaplastic large cell lymphoma is associated with t(2;5)(p23;q35), with a translocation of the anaplastic lymphoma kinase gene (producing the ALK or ALK1 protein) on chromosome #2 and the nucleophosmin gene on chromosome #5 (FISH for NPM/ALK fusion product; translocation diagram). The ALK rearrangement can be detected by fluorescence in situ hybridization (FISH) or by ALK immunohistochemical staining . In a recent study of children, FISH identified a translocation in 83% of cases and ALK immunostaining was present in 97% of cases (Br J Haematol 2005;131:624)
The differential diagnosis includes various carcinomas (usually keratin positive), Hodgkin’s lymphoma (has few neoplastic cells, usually CD15+, PAX5/BSAP+, ALK-, EMA-), anaplastic variant of diffuse large cell lymphoma (PAX5/BSAP+, usually CD20+, CD79a+), lymphomatoid granulomatosis (angiocentric, with a background of reactive lymphocytes and histiocytes, EBV+), and nonneoplastic disorders with atypical CD30+ cells.
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