Final Diagnosis -- Anaplastic large cell lymphoma, favor small cell variant



Anaplastic large cell lymphoma (ALCL) is the most common peripheral T-cell lymphoma in children and young adults, and the finding of adenopathy with skin lesions is characteristic. The majority of patients present with peripheral adenopathy, and skin lesions can be seen in a third to two-thirds of patients. Although a tumor nodule is more common, a rash (as seen in this patient) also occurs. Erythema overlying an affected lymph node (periadenitis) has also been described.

The characteristic diagnostic features include a cohesive large-cell infiltrate with paracortical or sinus growth in the lymph node, CD30 positivity in all tumor cells, a T-cell or null phenotype, and t(2;5) in most cases. Histologically, classic ALCL can be subclassified into either pleomorphic (large cells with irregular, indented or embryoid nuclei) or monomorphic (smaller cells with minimal cytologic variability). A small cell variant consists predominantly of small, irregular lymphocytes with a minor population of large CD30+ cells. Other variants have also been described, and include sarcomatoid and lymphohistiocytic.

The skin infiltrate can demonstrate a variable appearance, but usually corresponds to ALCL seen elsewhere. In this patient, the cutaneous infiltrate demonstrated an immunohistochemical phenotype largely similar to that seen by flow cytometry on the peripheral blood: the cells were positive for CD2, CD3, CD4 and CD7, and negative for CD8; there was also increased CD30 staining.

A bone marrow biopsy demonstrated increased lymphocytes by H&E, but abnormal cells were difficult to visualize. Immunohistochemistry (IHC) showed these to be primarily T cells, with expression of CD2, CD3 and CD4, and decreased expression of CD5 and CD8. Cells positive for ALK-1 and CD30 were also identified. Bone marrow involvement is generally uncommon, except in the small cell variant of ALCL. The characteristically subtle tumor involvement is well demonstrated with this case.

ALCL is frequently associated with t(2;5)(p23;35) - a translocation between the nucleophosmin gene on chromosome 5 with the anaplastic lymphoma kinase gene on chromosome 2. While the highest sensitivity for diagnosis is with molecular methods, immunohistochemistry with ALK-1 for the anaplastic lymphoma kinase protein is also available. ALK expression correlates closest with the T-cell or null phenotype, and monomorphic or small cell variant phenotype. ALCL associated with B-cell phenotype, primary cutaneous presentation, and Hodgkin disease are t(2;5) negative.

However, ALK positivity is not required for diagnosis, although this point is controversial. Recently, KJ Savage et al reviewed the prognostic difference between peripheral T-cell lymphoma (PTCL), and ALK positive and ALK negative ALCL. Twenty-two institutions contributed 1314 cases of peripheral T-cell lymphoma, which were reviewed; 181 ALCL cases were identified. These cases were further subdivided into systemic versus primary cutaneous ALCL, and within these subsets, analysis for ALK was performed. It was found that while primary cutaneous ALCL had the best overall survival (90%), these cases had a relatively high rate of relapse (55%). In terms of the NPM-ALK translocation, those ALCL cases which were negative appeared similar in prognosis to PTCL, which is worse than ALK positive ALCL (see table below). Their conclusions recommend that clinicians be informed of the ALK status for patients with ALCL, as this markedly affects prognosis.

After diagnosis, the patient was treated with chemotherapy; however, she presented to the hospital several days later with recurrent skin lesions. Campath was administered. Central nervous system (CNS) involvement was radiologic evaluation, and because of slight enhancement, cerebrospinal fluid was obtained. This specimen, the most current one evaluated in pathology, demonstrated involvement by the presence of malignant cells. Therefore, a line was placed for administration of intrathecal chemotherapy.


  1. Jaffe ES, et al. Tumors of Hematopoietic and Lymphoid Tissues. World Health Organization Classification of Tumors. Lyon: IARC Press, 2001.
  2. Savage KJ, et al. "ALK-negative anaplastic large-cell lymphoma (ALCL) is clinically and immunophenotypically different from both ALK-positive ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project." Blood. Publ. on-line 2 April 2008.
  3. Swerdlow S and Collins R. Pediatric Hematopathology. Churchill Livingstone, 2001.

Contributed by Alicia F. Liang, MD, Lydia Contis, MD, and Fiona Craig, MD

Case IndexCME Case StudiesFeedbackHome