Faculty Bibliography

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.

We present a 56-year-old man with a two-year history of erythematous nodules and plaques on the forehead, frontal aspect of the scalp, and left side of the neck. Histopathologic findings are compatible with a diagnosis of diffuse large B-cell lymphoma (DLBCL). We present a brief review of primary cutaneous DLBCLs and address the putative association between DLBCLs and hepatitis C virus infection.

Necrobiotic xanthogranuloma (NXG) is a rare, chronic, progressive, non-Langerhans histiocytosis that is strongly associated with hematologic malignant conditions. Only about 100 cases have been reported in the literature since it was first described in 1980. It is important for dermatologists to recognize NXG and initiate a prompt hematologic evaluation. IgG kappa is the most frequently discovered monoclonal gammopathy (65%), followed by IgG lambda (35%), and, much less commonly, IgA. Although no modality has been shown to be consistently effective, therapeutic options include glucocorticoids (topical, intralesional, and/or systemic), alkylating agents (chlorambucil and cyclophosphamide). interferon alpha, antimetabolites, antibiotics, thalidomide, and plasmaphersis.

We present a case of cutaneous sarcoidosis in a 77-year-old woman without systemic disease, who presented with two subtypes of lesions: erythematous and hyperpigmented macules on the arms and anterior upper legs and erythematous, hyperkeratotic nodules, some crateriform, on the lower legs and feet. Whereas cutaneous sarcoidosis is present in up to one-third of cases and may present with a wide variety of lesions, verrucous sarcoidosis is uncommon. Diagnosis is by clinical and histopathologic exclusion of other entities, which include other causes of granulomatous inflammation such as infections and foreign-body reactions. Management options include topical, intralesional, or systemic glucocorticoids, antimalarials, tetracycline derivatives, and methotrexate.

Poikilodermatous mycosis fungoides (MF) is a variant of MF, formerly referred to as poikiloderma vasculare atrophicans. The lesions are classically characterized by large plaques of hypopigmentation and hyperpigmentation with atrophy and telangiectases. The plaques may be asymptomatic or mildly pruritic and typically involve the major flexural areas and trunk. Poikilodermatous MF has an early stage (IA-IIA) at diagnosis and a male predominance. Poikilodermatous MF shows an atypical T-cell infiltrate in the papillary dermis with evidence of epidermotropism, epidermal atrophy, dilated blood vessels in the dermis, melanophages, and melanin incontinence. Recent studies suggest a predominance of a CD8+, CD4- immunophenotype. Treatment modalities are similar to classic MF with phototherapy being the most common first-line therapy. Poikilodermatous MF has an excellent prognosis.

Linear morphea of the forehead or en coup de sabre (ECDS) is an unusual variant of morphea. It typically occurs in children although cases of adult-onset ECDS exist as reported here. ECDS has a specific distribution on the frontal scalp and forehead and is usually unilateral. Sclerosis in ECDS lesions may invade deeply to involve underlying muscle and bone and may exist on the same clinicopathologic spectrum as Parry-Romberg syndrome. Extracutaneous involvement is frequent, with neurologic and ophthalmologic findings occurring most commonly. The etiology of ECDS is unclear but may be autoimmune in origin. The question of whether Borrelia infection also plays a role remains controversial. Current evidence supports first-line treatment with methotrexate and oral glucocorticoids followed by phototherapy and mycophenolate mofetil.

We report a 79-year-old man with a 15-year history of elongated, finger-like, erythematous patches that are symmetrically distributed on his flanks and of small, <5 cm, erythematous, slightly scaly, round-oval patches on the upper and lower extremities. The lesions were occasionally pruritic and waxed and waned over the years. His clinical and histopathologic data indicated small-plaque parapsoriasis, which is a benign entity that has been the center of controversy over the years, owing to its similarities to large-plaque parapsoriasis, which is on a spectrum with mycosis fungoides.

Physician interaction with the pharmaceutical industry raises many ethical concerns. This relationship is complex, owing to a pluralism of beliefs held by physicians, patients, and third parties. As a result, determining whether physicians fulfill their responsibilities to both the professional and public communities is an arduous endeavor. In an effort to clarify the situation and provide transparency to this complex relationship, medical and pharmaceutical organizations have enacted their own respective codes and guidelines. Even with adherence to these guidelines, questions remain regarding the codependent relationship that interweaves the pharmaceutical industry with the medical community. Owing to the ever-changing landscape enmeshing product development, scientific advancement, corporate realities and patient care, the proper choice for physicians is rarely obvious; however, to operate to the highest standards, those in the medical community must be candid about relations with the pharmaceutical industry and transparent in their financial interests. Further undertakings should focus not on the eradication of physician-pharmaceutical interaction, but instead on the education of physicians about industry marketing strategies and the delineation of boundaries of these interactions to benefit not the individual physician, but our patients.

A 44-year-old African American woman presented with well-demarcated, pruritic and intermittently painful plaques and subsequently a diagnosis of mycosis fungoides stage IB was made. Six months after diagnosis, cutaneous tumors developed despite treatment with narrow-band ultraviolet B phototherapy. The patient failed low-dose methotrexate treatment and is now slowly improving on combination therapy with subcutaneous interferon alfa and oral bexarotene. This patient demonstrates the progression of patch/plaque stage disease to cutaneous tumors. Her case highlights the use of interferon and combination therapies in more advanced mycosis fungoides and demonstrates potential difficulties encountered in treating skin of color.