Gladys H. Telang

Syndrome of Cocaine-Levamisole-Induced Cutaneous Vasculitis and Immune-Mediated Leukopenia

OBJECTIVE We describe 4 patients who presented with palpable purpura, arthralgia or arthritis, leukopenia, and antineutrophil cytoplasmic antigen (ANCA) positivity most likely as a result of a hypersensitivity reaction to cocaine-levamisole induced vasculopathy. METHODS Cases were seen and reviewed in both the inpatient consult service and the outpatient clinics at Rhode Island Hospital from August 2009 to August 2010. Clinical characteristics as well as pertinent laboratory parameters were also reviewed and corroborated with a review of the present literature. RESULTS We describe 3 cases of cocaine-levamisole-related cutaneous vasculitis with or without associated neutropenia, and 1 case of severe neutropenia with oral mucosal ulceration. Further serologic studies revealed maximum titers of ANCA mostly in a perinuclear pattern. Antimyeloperoxidase tested negative or mildly elevated in our cohort. Three patients with neutropenia had positive antigranulocyte IgM antibody. Nonsteroidal anti-inflammatory drugs were effective as first-line treatment for joint pain. The use of colchicine and systemic corticosteroid was employed to manage severe and persistent skin lesions. CONCLUSIONS Cocaine-levamisole-related cutaneous vasculitis with leukopenia is a diagnosis of exclusion, but this diagnosis should be strongly considered in patients with a history of cocaine abuse who present with a tetrad of cutaneous manifestations consisting of palpable purpura or bullae with ear involvement, arthralgias, leukopenia, and positive ANCA in high titers and negative Antimyeloperoxidase, when other infectious or idiopathic vasculitic entities have been excluded.

Onychopapilloma presenting as longitudinal leukonychia

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Subungual Myxoid Pleomorphic Fibroma

The authors report an example of pleomorphic fibroma in a unique site: the subungual space of the thumb. A 54-year-old man presented with paronychia and markedly thickened hyperkeratotic nail. The nail plate was removed, and an exophytic, red, friable, granulation tissue-like lesion was revealed subungually. The lesion was diagnosed clinically as pyogenic granuloma. Excisional biopsy was performed. Histologically, the lesion showed a hypocellular fibroma with myxoid areas and dilated blood vessels. Interspersed with ordinary appearing fibroblasts, there were bizarre, atypical fibroblasts with hyperchromatic and large, pleomorphic nuclei and multinucleated floret-like giant cells. These atypical cells showed strong immunoreactivity with antibodies against CD34 and vimentin. Occasional positivity was noted with factor XIIIa and alpha-1-antichymotrypsin, whereas no reactivity occurred with alpha-1-antitrypsin, actin, or S-100 protein. The entity of pleomorphic fibroma has been reported in many body sites; however, this is the first case to be reported in the subungual space.

Melanoma and squamous cell carcinoma on different nails of the same hand

Nail dyschromia, including melanonychia and erythronychia, encompasses a wide range of possible diagnoses. While the majority of these lesions are benign, malignancies of the nail unit represent a sinister, and potentially life-threatening, cause of nail dyschromia. Unfamiliarity with tumors of the nail apparatus can lead to a delay in diagnosis. A case is presented of a patient with two separate and concurrent malignant neoplasms of the nail unit, on different nails on the same hand, each featuring an unusual clinical presentation: amelanotic melanoma presenting as longitudinal erythronychia and squamous cell carcinoma in situ presenting as longitudinal melanonychia. This presentation underscores the need for a low threshold for biopsy in the presence of nail dyschromia of uncertain etiology.

Thomsen-Friedenreich (T) antigen: a possible tool for differentiating sebaceous carcinoma from its simulators.

The Thomsen–Friedenreich (T) antigen is a cryptic glycoprotein, referred to as tumor antigen or cancer-associated antigen because it is absent or masked by some carbohydrates in normal tissues, but present in many human cancers. The latter include gastrointestinal, lung, pancreatic, mammary, and some ovarian carcinomas. Cancer cells frequently undergo incomplete glycosylation resulting in the appearance of precursor structures that normally would be absent like the case with the T antigen. T antigen can be detected by several different reagents including monoclonal antibodies and several plant lectins–e.g., Arachis hypogea (peanut agglutinin). The aim of the current study was to evaluate the expression of T antigen in sebaceous carcinoma and to compare it with its simulators. The authors studied the immunohistochemical expression of T antigen in 45 skin biopsy and excisional specimens obtained from the archives of their dermatopathology laboratories, including 8 cases of sebaceous carcinoma, 15 cases of sebaceous adenoma, 9 cases of sebaceoma, 1 case of basal cell carcinoma with sebaceous differentiation, and 12 cases of basal cell carcinoma with cytologic atypia. Sebaceous carcinoma was unique in expressing a strong, diffuse cytoplasmic T antigen reactivity (7 of 8 cases) along the immature basaloid cells and the intermediate cells. However, sebaceous adenoma, sebaceoma, and basal cell carcinomas expressed negative reaction in the basaloid cells and mild reactivity in the intermediate cells. Mature sebocytes showed a strong reaction in all cases. The authors concluded that T antigen expression may be a helpful tool in differentiating sebaceous carcinoma from other sebaceous lesions that may simulate it histologically.

Subungual blue nevus with combined phenotypic features

Blue nail dyschromia may represent melanocytic, vascular, or other etiologies. A case of a subungual blue nodule is presented, with a pseudo-clubbed nail. On histopathologic examination, there was a combined subungual blue nevus, with features of a common blue nevus and a pigmented epithelioid melanocytoma. This unusual presentation is reviewed, with a discussion of blue nail dyschromia and subungual blue nevi.

Prognostic factors and risk stratification in early mycosis fungoides

Abstract Available demographic, clinical, histologic, immunohistochemical and laboratory findings, including serum cytokine/cytokine receptor levels, obtained at initial evaluation in a cohort of 33 patients with mycosis fungoides (MF) at stages I–IIA who had subsequent progression of disease were compared against 70 stage-matched cases of MF without observed progression. Significant factors that correlated with both disease progression and overall survival were: (1) presence of large Pautrier microabscesses (10 or more atypical lymphocytes), (2) presence of atypical lymphocytes with hyperchromatic or vesicular nuclei in the dermal infiltrate, (3) less than 20% CD8 + cells in the dermal infiltrate and (4) above normal (> 122 U/mL) serum immunoglobulin E (IgE) level. Combination of these factors was used to construct prognostic groupings which, if validated, might be useful to identify patients with clinically early MF at highest risk for disease progression and poor outcome.

Remission of primary cutaneous anaplastic large cell lymphoma after a brief course of brentuximab vedotin

Dear Editor, We evaluated a 74-year-old Caucasian man with multiple previous recurrences of primary cutaneous anaplastic large cell lymphoma (PCALCL) between 2003 and 2010 involving his scalp, forearms, shoulders, and trunk as solitary papules or nodules. They had been treated with excisions, topical carmustine, or focal electron beam radiotherapy (EBRT). In 2011, the patient received 4,000-cGy EBRT to a new lesion on the left calf and 3,600-cGy tomotherapy to adjacent tumors in January 2012. Treatment was complicated with extensive lymphedema, cellulitis, and ulcerative dermatitis requiring debridement, intravenous antibiotics and resulting in nonhealing wounds. In June 2012, numerous rapidly growing nodules appeared on the patient’s left thigh, without evidence of systemic involvement (Fig. 1a). Biopsy consistently demonstrated CD30-positive, anaplastic lymphoma kinase (ALK-1)-negative PCALCL (Fig. 1b). This multifocal recurrence necessitated systemic therapy, but the disease progressed with enlarging and new lesions within 3 weeks of starting oral methotrexate 15 mg weekly. Multiagent chemotherapy was considered hazardous in view of ongoing, debilitating wound complications. The patient consented to off-label treatment with brentuximab vedotin and received three infusions at 1.8 mg/kg every 21 days. All lesions regressed completely during the first cycle (Fig. 1c). No toxicity was observed except for grade 1 diarrhea lasting 7 days. In particular, no neutropenia or neuropathy occurred. The patient has been in continued remission for 3 months and continued recovery of mobility with specialized wound care. PCALCL differs from other cutaneous T cell lymphomas such as mycosis fungoides and from the systemic form of ALCL. It is composed of large anaplastic, pleomorphic, or immunoblastic T cells typically expressing CD30, but not ALK-1, and runs an indolent course with frequent, though limited cutaneous recurrences [1]. Therapy for this rare disease relies on case reports and series, particularly for the minority of patients with multifocal relapses or nodal involvement [2]. Surgical excision and radiotherapy have a curative potential for solitary lesions. Remissions with cytotoxic chemotherapy, occurring rapidly even after low-dose methotrexate or etoposide, are disappointingly short (months) in refractory cases, although retreatment is often successful [3–5]. Anecdotal responses to imiquimod, bexarotene, retinoids, interferon, and thalidomide have been reported [2]. Brentuximab vedotin is an anti-CD30 monoclonal antibody conjugate with a potent microtubule inhibitor monomethyl auristatin E [6]. With up to 16 doses in the pivotal phase II studies, it produced the remarkable 75 % response rate in refractory CD30-positive Hodgkin’s lymphomas relapsing after autologous stem-cell transplantation, and 86 % in recurrent systemic ALCL [7, 8]. Toxicities include peripheral sensory neuropathy, neutropenia, fatigue, nausea, and rare occurrences of progressive multifocal leukoencephalopathy in immunosuppressed patients [9]. The unconjugated anti-CD30 antibody SGN-30 had demonstrated activity against PCALCL, but its development was abandoned [10]. Although cost concerns limit the application of targeted therapy in PCALCL, our case may indicate that in patients medically unsuitable for combination chemotherapy, A. Desai :A. J. Olszewski (*) Division of Hematology–Oncology, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI 02860, USA e-mail: adam_olszewski@brown.edu

Lichen planus of the nail matrix with predominant plasma cell infiltrate

Lichen planus (LP) is an inflammatory dermatitis of idiopathic origin that can involve the skin, mucous membranes, hair and nails. Histologically, LP is characterized by compact orthokeratosis, wedge‐shaped hypergranulosis, irregular acanthosis, damage to the basal cell layer and a band‐like inflammatory infiltrate in the upper dermis. Lymphocytes are the predominant cells making up the infiltrate, along with a few macrophages, eosinophils and plasma cells. In addition, melanophages are often found in the upper dermis adjacent to the damaged basal cells. 1 We describe a patient with a lesion of the toenail clinically and histopathologically consistent with LP, but with a band‐like inflammatory infiltrate composed primarily of plasma cells. Previously, only three other cases of LP with plasma cell predominant infiltrate have been reported, none of which involved the nail matrix.

Sézary Syndrome Coexisting with B-Cell Chronic Lymphocytic Leukemia: Case Report and Review of the Literature

Introduction: The simultaneous presentation of chronic B-cell lymphocytic leukemia (B-CLL) and cutaneous T-cell lymphoma (CTCL) is extremely rare. Case Report: We describe a patient with B-CLL and Sézary syndrome (SS), an erythrodermic and leukemic variant of CTCL. Despite treatment, the SS progressed to involve internal organs and eventual death of the patient from sepsis. This is the first reported case of SS coexisting with chronic lymphocytic leukemia in which an anti-Vβ13.6 antibody was used to serially track changes in circulating neoplastic T cells vis-à-vis neoplastic B cells and to detect neoplastic T cells in ascitic fluid near the end of the patient’s life. Discussion: We speculate that the coexistence of B-CLL and CTCL is the result of an initiating genetic or epigenetic defect at the level of the common lymphoid stem cell that predisposes both B-cell and T-cell lineages to additional oncogenic changes at a more advanced stage of differentiation.