November 2006

Fig.4

Fig.5

Fig.6

Diagnosis: Recurrent anaplastic large T-cell lymphoma

Histopathology: A skin biopsy revealed a mononuclear cell infiltrate surrounding the superficial dermal vessels and adnexa. A mild infiltrate was also seen in the interstitum. The infiltrate was composed of intermediate sized, mononuclear cells with occasional irregular nuclear contours and inconspicuous nucleoli. Some atypical mitotic figures were seen in larger cells (see figures 4,5). Immunohistochemical analysis revealed CD30 and Alk-1 positive staining (see figure 7). The skin biopsy was consistent with a recurrence of her previously diagnosed anaplastic large t-cell lymphoma.

Further work-up:
A whole-body PET scan subsequently revealed a large lymph node mass in the anterior cervical space anterior to the thyroid, extending to the skin surface and corresponding to the palpable skin abnormality.
A bone marrow biopsy showed no evidence of lymphoma.
Her oncologist plans to treat her with salvage chemotherapy with an anti-CD30 monoclonal antibody called FGN30 in the hope of achieving a second complete remission. She will then undergo an allogenic stem cell transplant.

Discussion:

Anaplastic large cell lymphoma (ALCL) is a well-recognized subtype of non-Hodgkin lymphoma of T-cell lineage. It represents 15% of all non-Hodgkin lymphomas of children as well as 20 to 50% of the large cell lymphomas in children. It is characterized by a broad spectrum of histologic features and by the expression of CD30 (Ki-1) and ALK (anaplastic lymphoma kinase). Virtually all ALCLs seen in children are ALK-positive. The average age at diagnosis is 8 to 16 years, with a reported range of 1 to 15 years. Extranodal disease occurs in 40% of patients. The pathogenesis of systemic disease is linked to phosphorylation of a tyrosine kinase ALK resulting in unregulated growth of affected lymphoid cells. In most cases (70%), ALK expression is the result of the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the ALK locus at 2p23 to the NPM (nucleophosmin) gene locus at 5q35.

Clinically, ALCL is characterized by a high incidence of systemic symptoms such as fever, as well as extranodal disease. The most common sites involved include skin, bone, soft tissue, and lung. It often presents in advanced clinical stages with prominent B symptoms.

A combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the standard first-line treatment. Radiation therapy may also be necessary for remaining bulky lesions after the completion of chemotherapy. Compared to patients with other types of diffuse aggressive lymphomas, patients with ALCL have increased and more prolonged response rates, with improved overall survival. Prognostic factors for ALCL are the same as those for other non-Hodgkin lymphomas: age, LDH values, number of extranodal sites, and stage. ALK-positivity is a positive prognostic indicator; these patients have a 5-year survival rate of 70-80% versus 15-45% for those who are ALK-negative.

References:
1. Andrew's Diseases of the Skin (10th Edition). Elsevier Inc, 2006.
2. Dermatology. Jean Bolognia, Joseph L Jorizzo, Ronald P Rapini. Elsevier Inc., 2003.
3. Weedon D. Skin Pathology (2nd ed). Churchill-Livingstone,2002.
4. Kadin ME, Carpenter C. Systemic and primary cutaneous anaplastic large cell lymphomas. Semin Hematol. 2003 Jul;40(3):244-56.
5. Sebire NJ, Webb D, Ramsay AD. Anaplastic large cell lymphoma with ALK expression and presence of the t(2;5) translocation in a 5-month-old infant.
6. Fetal Pediatr Pathol. 2005 Jan-Feb;24(1):63-70.

This case was presented by Drs. Erica Rogers, Maria Canizares,Kimberly Crone, and Anne Lind.