Faculty Bibliography

We report an HIV-negative, 55-year-old manwith recurrent Kaposi's sarcoma (KS) of the lowerextremities, who does not fit into any of thefour previously described variants of KS: classicKS, AIDS-related KS, iatrogenic KS, and AfricanendemicKS. There are reports in the literature ofchildhood-onset KS, which is thought to be dueto an inherited immune deficiency that confers ahigher susceptibility to human Herpesvirus-8 (HHV-8), which is the virus that is known to cause KS. Ourpatient may be affected with an inherited immunedeficiency that has predisposed him to KS, and thismutation also may account for his prostate andbladder cancer.

BACKGROUND: The histopathologic diagnosis of mycosis fungoides (MF) has classically relied on the presence of atypical epidermotropic T-lymphocytes predominating over spongiosis. However, in some cases of MF, prominent epidermal mucinosis in a spongiosis-like pattern mimics a spongiotic dermatitis. To our knowledge, only one series in the literature has thus far recognized the presence of epidermal mucinosis in MF. METHODS: We evaluated 30 skin biopsies from 18 patients with the clinical diagnosis of MF, which fulfilled all histopathologic criteria for patch- or plaque-stage MF, but also showed epidermal mucinosis in a spongiosis-like pattern. Fifteen specimens were studied by immunohistochemistry, and 7 were tested for T-cell receptor (TCR) gene rearrangements. Twenty biopsies of spongiotic dermatitides were included as controls. RESULTS: We confirmed the presence of epidermal mucinosis in all 30 cases of MF with a spongiosis-like pattern based on histopathologic criteria and the colloidal iron stain for mucin. Immunohistochemistry in 14 out of 15 specimens showed marked loss of pan-T-cell antigens CD5 and CD7; and TCR clonality was detected in 7 specimens from 6 patients, supporting the diagnosis of MF CONCLUSIONS: We report helpful histopathologic criteria for distinguishing MF with epidermal mucinosis in a spongiosis-like pattern from spongiotic dermatitis.

We present a 64-year-old man with a three-year history of pruritic, pink papules and nodules of the face who was found to have a clonal lymphoproliferative B-cell disease that was characterized by a clonal IGH rearrangement. Although morphologic features present in the biopsy specimen were consistent with a reactive process, additional clinicopathologic correlation (anatomic presentation of lesions on the face, the absence of t(14:18) translocation, and bcl-2 and MUM1 expression) reinforced suspicion of a cutaneous B-cell lymphoma. Systemic work-up with CT/PET and a bone marrow biopsy ultimately excluded systemic disease and primary cutaneous follicle-center lymphoma (PCFCL) was a strong diagnostic consideration. The patient was treated with systemic rituximab with a partial resolution of the facial lesions. The case demonstrates both clinical and pathologic challenges to the diagnosis of primary cutaneous B-cell lymphoma (PCBCL). Furthermore, despite a newly refined classification system, the case also specifically highlights the persistent requirement for flexible clinical reasoning and pathologic correlation. Such reasoning is necessary to generate individualized strategies for diagnosis and treatment when cutaneous B-cell lymphoma is suspected.

Palpable migratory arciform erythema is a T-cell pseudolymphoma with no well-established treatment. The disease is rarely reported in the literature, perhaps because it is difficult to diagnose. We present a case of a variant of PMAE in a 30-year-old healthy man with no history of medication use and erythematous to violaceous annular and arciform plaques on his face, scalp and trunk. This case is of particular significance because gene rearrangement studies and histopathologic findings are concerning for folliculotropic mycosis fungoides while the clinical course does not support this diagnosis. The authors' emphasize that clinical history is imperative for definitive diagnosis of palpable migratory arciform erythema as it can clinically and histopathologically resemble other cutaneous lymphocytic diseases

J Drugs Dermatol 2014;13(10):1288-1289.

Notch signaling is essential for the development of T cell progenitors through the interaction of NOTCH1 receptor on their surface with the ligand, Delta-like 4 (DLL4), which is expressed by the thymic epithelial cells. Notch signaling is quickly shut down once the cells pass beta-selection, and CD4/CD8 double positive (DP) cells are unresponsive to Notch. Over the past two decades a number of papers reported that over-activation of Notch signaling causes T cell acute lymphoblastic leukemia (T-ALL), a cancer that prominently features circulating monoclonal CD4/CD8 double positive T cells in different mouse models. However, the possible outcomes of Notch over-activation at different stages of T cell development are unknown, and the fine timing of Notch signaling that results in T-ALL is poorly understood. Here we report, by using a murine model that ectopically expresses DLL4 on developing T cells, that the T-ALL onset is highly dependent on a sustained Notch activity throughout the DP stage, which induces additional mutations to further boost the signaling. In contrast, a shorter period of Notch activation that terminates at the DP stage causes a polyclonal, non-transmissible lymphoproliferative disorder that is also lethal. These observations resolved the discrepancy of previous papers on DLL4 driven hematological diseases in mice, and show the critical importance of the timing and duration of Notch activity.

A 35-year-old man initially was referred for management of recalcitrant urticaria. Owing to his long history of arthritis and sensorineural hearing loss, genetic testing was performed. The test showed a D305N heterozygous mutation in the NLRP3 gene, which is consistent with the diagnosis of Muckle-Wells syndrome. We discussed the rationales behind the use of the interleukin-1 antagonist anakinra in this autoinflammatory disorder.

Morphea and lichen sclerosus et atrophicus (LSA) have similar clinical presentations. Reports of patients with overlapping clinical and histopathologic features of both conditions have led some to speculate that they may represent different presentations along the same disease spectrum. It has been postulated that there is a common etiologic agent, which may involve autoimmunity, response to trauma, or infection. The link between Borrelia infection and both morphea and LSA has been widely studied but remains controversial. We present a case of a patient with lesions characterized by overlapping features of morphea and LSA with rapid decrease in joint mobility.