CORRECT DIAGNOSIS:

Primary Cutaneous Anaplastic Large-Cell Lymphoma

DISCUSSION:

Primary cutaneous lymphomas (PCL) are defined as the clonal proliferation of lymphocytes in the skin and can be classified according to the predominant tumor cell population; namely cutaneous T-cell lymphomas, cutaneous B cell lymphomas and cutaneous lymphomas from the natural killer or plasmacytoid dendritic cells. PCLs are the second most common type of extranodal Non-Hodgkin’s lymphoma, falling behind only to gastrointestinal lymphomas. The annual incidence of PCL has been estimated to be roughly 1 in 100,000.

Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a type of Non-Hodgkin’s T-cell lymphoma that has no clinical sign of extracutaneous involvement at the time of diagnosis. This condition predominately affects adults with a male to female ratio of 2:1. Typically C-ALCL presents as a solitary or localized nodule or tumor, often with central ulceration. Some case reports state that the tumors may spontaneously heal, however, most lesions do not regress and often exhibit a high rate of cutaneous recurrences. Roughly 10% of patients will have extracutaneous involvement at the time of diagnosis, usually due to the involvement of regional lymph nodes.

Histopathology of C-ALCL consists of large pleomorphic cells with hyperchromatic nuclei and prominent nucleoli, displaying areas of necrosis, mitoses, and an eosinophilic infiltrate. Immunohistochemical stains are key in making the diagnosis, with greater than 75% of tumor cells expressing CD30 positivity. In addition, staining will be negative for ALK (anaplastic lymphoma kinase) and EMA (epithelial membrane antigen). Clonal T-cell receptor (TCR) gene rearrangements will be present. An important distinction from CD30+ systemic anaplastic large cell lymphoma with secondary skin involvement is ALK and EMA positivity. Of note, a chromosomal translocation at t(2:5)(p23;q35) occurs in 40-60% of patients with systemic anaplastic large cell lymphoma, resulting in the formation of the chimeric protein NPM-ALK (nucleophosmin-anaplastic lymphoma kinase).

Prognosis of C-ALCL for patients with the limited disease is favorable with an estimated 5-year survival of approximately 95%.

Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a type of Non-Hodgkin’s T-cell lymphoma. Typically C-ALCL presents as a solitary or localized nodule or tumor, often with central ulceration. Some case reports state that the tumors may spontaneously heal, however, most lesions do not regress and often exhibit a high rate of cutaneous recurrences. Roughly 10% of patients will have extracutaneous involvement at the time of diagnosis, usually due to the involvement of regional lymph nodes.

TREATMENT:

Treatment of C-ALCL is largely dependent on the tumor burden. Solitary tumors are treated with surgical excision and/or radiotherapy, while multifocal disease requires multiagent chemotherapy, most commonly treated with CHOP.

Our patient is currently being followed by hematology/oncology and radiation oncology, where he is undergoing four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy along with radiation.

REFERENCES:

Amin, H. M., & Lai, R. (2007). Pathobiology of ALK+ anaplastic large-cell lymphoma. Blood, 110(6), 2259-2267. https://doi.org/10.1182/blood-2007-04-080525

Duvic, M. (2011). CD30+ neoplasms of the skin. Current Hematologic Malignancy Reports, 6(4), 245-250. https://doi.org/10.1007/s11899-011-0087-8

Fung, M. A., Murphy, M. J., Hoss, D. M., et al. (2002). Practical evaluation and management of cutaneous lymphoma. Journal of the American Academy of Dermatology, 46(3), 325-357. https://doi.org/10.1067/mjd.2002.122096

Kadin, M. E., Pinkus, J. L., Pinkus, G. S., et al. (2008). Primary cutaneous ALCL with phosphorylated/activated cytoplasmic ALK and novel phenotype: EMA/MUC1+, cutaneous lymphocyte antigen negative. American Journal of Surgical Pathology, 32(10), 1421-1426. https://doi.org/10.1097/PAS.0b013e31817c3c7a

Kempf, W., Pfaltz, K., Vermeer, M. H., et al. (2011). EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: Lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Blood, 118(21), 4024-4035. https://doi.org/10.1182/blood-2011-06-364447

Klemke, C. D. (2013). Cutaneous lymphomas. Journal der Deutschen Dermatologischen Gesellschaft, 11(11), 1000-1002. https://doi.org/10.1111/ddg.12104

Querfeld, C., Khan, I., Mahon, B., et al. (2010). Primary cutaneous and systemic anaplastic large cell lymphoma: Clinicopathologic aspects and therapeutic options. Oncology, 24(6), 574-587.

Willemze, R., & Belijaards, R. C. (1997). EORTC classification for primary cutaneous lymphomas: A proposal from the cutaneous lymphoma study group of the European Organization for Research and Treatment of Cancer. Blood, 90(1), 354-371. https://doi.org/10.1182/blood.V90.1.354