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Anaplastic Large Cell Lymphoma Involving the Bone Marrow

View larger version (147K): [in this window] [in a new window]   Figure 1. A 15-year-old male presented to his primary care physician with a one month history of bilateral cervical lymphadenopathy, fever, night sweats, malaise, and weight loss. Subsequent PET scans demonstrated increased metabolic activity in multiple lymph nodes as well as diffuse bone marrow involvement. Hematological parameters were as follows: hemoglobin 13 g/dL, hematocrit 38%, WBC 9,800/mm³, platelets 148,000/mm³. A touch preparation of the bone marrow biopsy revealed the presence of numerous large cells with abundant vacuolated, basophilic cytoplasm and demonstrating pleomorphic nuclear features. Several of the nuclei were embryoid in shape and eccentrically placed, consistent with "hallmark" cells of anaplastic large cell lymphoma i.e. cells with horseshoe nuclei. The majority of malignant cells, however, as shown in this image were rather pleomorphic (see arrows). All cells of interest contain clumped chromatin and prominent nucleoli.

View larger version (100K): [in this window] [in a new window]   Figure 2. This is a higher magnification of one of the anaplastic large cells noted in the marrow aspirate. Note the eccentrically located embryoid nucleus containing numerous prominent nucleoli and the voluminous vacuolated and granulated cytoplasm. Cells such as these were found dispersed among other large, pleomorphic cells in the bone marrow aspirate.

View larger version (155K): [in this window] [in a new window]   Figure 3. Bone marrow biopsy reveals diffuse infiltration by the malignant cells, essentially obliterating most of the normal hematopoietic elements. Note the presence of numerous anaplastic-appearing large cells interspersed among a background of large pleomorphic malignant cells. The vesicular nuclei and prominent nucleoli are well illustrated. The anaplastic cytoplasm-rich cells seem to cluster into nodules, almost giving the impression of an infiltrating metastatic solid tumor. Mature polymorphs and an apparent abundance of eosinophils can be identified in the background. Mitotic figures are present.

View larger version (148K): [in this window] [in a new window]   Figure 4. A higher magnification of the previous image is shown which further demonstrates the morphologic features of the malignant cells. The pleomorphism is clearly evident. Note the presence of a large anaplastic cell with a horseshoe nucleus in the center (large arrow), as well as several smaller atypical cells with more round vesiculated nuclei dispersed throughout the infiltrate (small arrows). Mitotic figures are readily identified.

View larger version (176K): [in this window] [in a new window]   Figure 5. This low magnification view lends perspective to the extent of bone marrow involvement and demonstrates two distinct infiltrative patterns. In addition to the common type, several ALCL variants have been identified. These include the small-cell and lymphohistiocytic sub-types, as well as other patterns not designated as official variants, such as the giant cell-rich, sarcomatoid, and signet ring cell-rich patterns. Up to 10% of ALCL tumors demonstrate more than one histological variant. This image reveals sheets of malignant cells infiltrating the marrow on the left, which develop into a dense region of sarcomatoid-like growth on the right, comprised of cells of characteristic morphology mingling with spindled cells.

View larger version (174K): [in this window] [in a new window]   Figure 6. This higher power image focuses on a sarcomatoid-like region. Whether the spindled cells represent tumor cells or a desmoplastic response to the malignancy is unclear.

View larger version (102K): [in this window] [in a new window]   Figure 7. The malignant cells stain positive for ALK1 (anaplastic large cell kinase) by immunohistochemistry. Note that the staining pattern in this case is exclusively cytoplasmic, with the nuclei apparently devoid of ALK1. ALK1 staining is relatively specific for ALCL, as the protein is not known to be expressed in any other hematopoietic malignancies aside from a rare form of plamacytoid diffuse large B-cell lymphoma expressing cytoplasmic IgA. ALK1 expression is the most important prognostic factor in ALCL, and these tumors have an average 80% 5-year survival rate, as compared to 40% for ALK1-negative ALCL.

View larger version (167K): [in this window] [in a new window]   Figure 8. Immunohistochemical staining for CD30 is strongly positive in the malignant cells. Note the typical plasma membrane and Golgi staining. These cells also stain positive for EMA (epithelial membrane antigen), and the staining pattern resembles that of CD30 (not shown).

View larger version (153K): [in this window] [in a new window]   Figure 9. The malignant cells stain positive for the T-cell membrane protein CD43, as is evident in two thirds of cases. ALCL cells may also be positive for additional T-cell cytoplasmic membrane markers, such as CD3, CD4, CD5, or CD8. The malignant cells in this case stained positive for CD5 (not shown). In addition, they tend to stain with markers such as perforin, TIA-1, and granzyme B, which reflect the cytotoxic T-cell origin of the tumor.

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This Article Figures Only Services Similar articles in this journal Alert me to new content in the Image Bank Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lazarchick, J. Articles by Krings, G. Search for Related Content PubMed Articles by Lazarchick, J. Articles by Krings, G. Related Collections T-Cell and NK-Cell Neoplasms Related ASH-SAP Chapter Related Image Bank Image Sets Related ASH Education Book Article Social Bookmarking                   What's this?