Fatal Case of Primary Cutaneous Aggressive T-Cell Lymphoma Switching From a CD4+ to a CD8+ Phenotype: Progressive Disease With Bexarotene and Romidepsin Treatment.

A 77-year-old white male presented to the clinic with two isolated cutaneous tumors on his forehead. A cutaneous biopsy showed a focally folliculotropic CD4 cutaneous lymphoma. The tumors were irradiated with a complete response, and he was started on oral bexarotene. He experienced localized cutaneous relapse 3 months into treatment. These new tumors now revealed a surprisingly CD8 cytotoxic phenotype, but with the same clone. A systemic workup was negative. His regimen was switched to romidepsin, and he was treated with local radiation again. Another 3.5 months passed in remission until he developed widespread cutaneous tumors. Positron emission tomography/computed tomography revealed multifocal systemic disease involving his diaphragm, liver, distal duodenum, proximal jejunum, anterior chest wall including pectoral muscles, and lungs without significant adenopathy. He died a few days later. Given his full clinical and pathological course, he was given the diagnosis of an aggressive primary cutaneous T-cell lymphoma, unspecified.

Morphea-like lesion following topical endectocide application in a cat.

BACKGROUND: Scleroderma is a rare chronic disease of connective tissues that may affect the skin in humans. Although still unclear, its aetiology may be related to drug reactions. To date, scleroderma has been reported in only a few dogs and one cat. CASE REPORT: Localized (morphea-like) scleroderma was diagnosed in a 3-year-old intact male Persian cat that developed a nonpruritic, well-demarcated alopecic plaque a few days after topical application of a 'spot-on' solution containing praziquantel and emodepside. The lesion occurred at the site of application at the dorsal cervical region, and was characterized histologically by fibrosing dermatitis. There was no response to systemic treatment with pentoxifylline. Following topical therapy with minoxidil 5% for 30 days, hair regrowth occurred, and the lesion had completely disappeared after 60 days. CONCLUSIONS AND CLINICAL IMPORTANCE: The relationship between the alopecic plaque and the topical application of the spot-on solution cannot be proved; however, according to the Naranjo scale, which estimates the probability of adverse drug reactions, this case could be classified as a 'possible' reaction to one of the components of the product. Sclerodermoid reactions have not been described as a cutaneous drug eruption in veterinary medicine, so this case may possibly represent the first such idiosyncratic reaction to one of the applied substances. Furthermore, to the best of the authors' knowledge, this is the second report of a morphea-like lesion in a cat.

The cytotoxic activity of Aplidin in chronic lymphocytic leukemia (CLL) is mediated by a direct effect on leukemic cells and an indirect effect on monocyte-derived cells.

Aplidin is a novel cyclic depsipeptide, currently in Phase II/III clinical trials for solid and hematologic malignancies. The aim of this study was to evaluate the effect of Aplidin in chronic lymphocytic leukemia (CLL), the most common leukemia in the adult. Although there have been considerable advances in the treatment of CLL over the last decade, drug resistance and immunosuppression limit the use of current therapy and warrant the development of novel agents. Here we report that Aplidin induced a dose- and time-dependent cytotoxicity on peripheral blood mononuclear cells (PBMC) from CLL patients. Interestingly, Aplidin effect was markedly higher on monocytes compared to T lymphocytes, NK cells or the malignant B-cell clone. Hence, we next evaluated Aplidin activity on nurse-like cells (NLC) which represent a cell subset differentiated from monocytes that favors leukemic cell progression through pro-survival signals. NLC were highly sensitive to Aplidin and, more importantly, their death indirectly decreased neoplasic clone viability. The mechanisms of Aplidin-induced cell death in monocytic cells involved activation of caspase-3 and subsequent PARP fragmentation, indicative of death via apoptosis. Aplidin also showed synergistic activity when combined with fludarabine or cyclophosphamide. Taken together, our results show that Aplidin affects the viability of leukemic cells in two different ways: inducing a direct effect on the malignant B-CLL clone; and indirectly, by modifying the microenvironment that allows tumor growth.