FINAL DIAGNOSIS: CD30 POSITIVE LYMPHOPROLIFERATIVE DISORDER
This case illustrates the diagnostic challenges posed by a group of disorders known as CD30 positive lymphoproliferative disorders of the skin. Comprising this group are lymphomatoid papulosis (LYP), primary cutaneous anaplastic lymphoma (C-ALCL), and borderline cases. The differential diagnosis in the case presented includes LYP-Type C, C-ALCL, and skin involvement by systemic anaplastic large cell lymphoma.
Lymphomatoid papulosis is characterized by multiple papules and nodules, which regress spontaneously. Three histologic subtypes have been described, which represent a spectrum with overlapping features and do not carry prognostic significance. Type A lesions have a few tumor cells in a background of inflammatory cells including neutrophils, eosinophils, and histiocytes. Type B lesions are characterized by epidermotropic lymphocytes with cerebriform nuclei mimicking mycosis fungoides. Type C lesions have sheets of large atypical lymphoid cells with only a few admixed inflammatory cells. The large atypical lymphoid cells are though of T cell origin. Various histologic types may be present in individual patients at the same time. In LYP types A and C the large atypical cells express CD30, CD3, and CD4. CD2 and CD5 are usually expressed. These cells also express the cytotoxic markers TIA-1 and granzyme. The large atypical cells do not express CD8, CD7, or CD56. The cells may lose expression of CD3. In LYP type B the atypical cells are usually CD30 negative. Five year survival rates for LYP are 100%; however up to 20% of patients develop LYP-associated malignant lymphomas (mycosis fungoides, Hodgkin lymphoma, systemic or cutaneous CD30+ large T-cell lymphoma), which result in a fatal outcome of 2% of patients.
Primary cutaneous anaplastic large cell lymphoma is composed of large atypical to anaplastic appearing lymphoid cells. This disease mainly affects adults with a peak in the sixth decade, but cases have been reported in children. It usually presents as a solitary rapidly growing nodule. The skin overlying the lesion may ulcerate. Histologically the cells grow in sheets. Mitotic figures are frequent. Clusters of small reactive lymphocytes are found within and around the tumor cells. The malignant cells express CD2, CD3, CD4, CD30, and cytotoxic markers including TIA-1, granzyme, and perforin. Loss of T-cell antigen expression is not infrequent. The malignant cells do not express EMA or ALK. Five year survival rates approach 90%. Interestingly, up to 40% of C-ALCL show spontaneous regression similarly to LYP.
The case in question has overlap of clinical, histologic and immunophenotypic features between LYP and C-ALCL. The history of appearing and regressing nodules suggests LYP except one that grew fairly rapidly. Neither the histology nor the immunophenotype was able to differentiate between LYP type C and C-ALCL. Flow studies and cytogenetics were not conclusive. Systemic involvement was ruled out by imaging studies, which was supported by the negative ALK and EMA immunostains. Therefore, this lesions best fits in the borderline category of CD30 positive lymphoproliferative disorder. Of note, genetics studies have not proven to be helpful because no specific alteration has been found. The translocation t(2;5) characteristic of systemic anaplastic large cell lymphomas are not present in either LYP or C-ALCL and T-cell receptor gene rearrangements have been observed in both lesions.
Skin tumors, WHO Classification of Tumors, IARC Press, 2006, pages 179-181
Contributed by Joel F. Gradowski, MD and Csaba Galambos, MD