Unique Cutaneous Reaction to Second- and Third-Generation Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia.

BACKGROUND: Recently developed tyrosine kinase inhibitors (TKIs) offer first-line alternatives to patients with chronic myeloid leukemia. While these medications are generally well tolerated, cutaneous reactions occur frequently and can present a management challenge. We describe a newly recognized skin reaction to dasatinib and nilotinib and extend it to the newer agent ponatinib. OBSERVATIONS: Nine patients developed varying degrees of a clinically and histopathologically lichenoid exanthem comprised of erythematous, predominately follicular papules with scale and alopecia. The pattern is reminiscent of the scarring and nonscarring alopecia of follicular lichen planus/lichen planopilaris (LPP) with keratosis pilaris-like LPP--the rare Graham-Little-Piccardi-Lassueur syndrome. Importantly, the accompanying pruritus can be severe enough to result in discontinuation of therapy. CONCLUSIONS: Clinicians should be aware of this unusual eruption to the newer TKIs and the potential therapeutic challenges. Understanding these eruptions may also suggest potential mechanisms in the idiopathic forms of follicular lichen planus.

Idiopathic lymphoplasmacellular mucositis-dermatitis of the eyelid.

Idiopathic lymphoplasmacellular mucositis-dermatitis is a rare mucosal or cutaneous disorder characterized clinically by papules or plaques with variable erosion and microscopically by dense dermal inflammatory cell infiltrates with numerous plasma cells. It has been described in the oral and upper aerodigestive tracts, male and female genitalia, and other mucosal surfaces. In this article, the authors describe a case of idiopathic lymphoplasmacellular mucositis-dermatitis occurring in the skin of the eyelid that was removed by excisional biopsy and has not recurred in the 19-month follow-up period.

Fatal ALK-negative systemic anaplastic large cell lymphoma presenting with disseminated cutaneous dome-shaped papules and nodules.

Anaplastic large cell lymphoma (ALCL) is classified as a CD30 positive non-Hodgkin lymphoma. Systemic ALCL (S-ALCL) is further subdivided into two subgroups based on anaplastic lymphoma kinase (ALK) expression. In systemic ALCL, positive ALK expression correlates with a favorable prognosis, whereas negative ALK expression correlates with poorer overall survival. By definition, primary cutaneous ALCL (cut-ALCL) is limited to the skin and is uniformly ALK-negative. Cut-ALCL closely resembles LyP with regards to its benign clinical course and CD30 positivity. We describe a unique case of ALK-negative (ALK-) S-ALCL presenting with cutaneous disseminated dome-shaped papules.

A report of Epstein-Barr virus-positive primary cutaneous natural killer-/T-cell lymphoma.

We describe a patient who presented with Epstein-Barr virus-positive tumor-stage primary cutaneous lymphoma. Our patient had previously been treated with oral methotrexate for long-standing rheumatoid arthritis. Tissue analysis revealed large tumor cells that were surface CD2- and CD3-positive; T-cell-restricted intracellular antigen-positive; CD56-, CD20-, and CD30-negative; and stained positively for Epstein-Barr virus. Our case is noteworthy for several reasons. Although the presence of rheumatoid arthritis and therapy with methotrexate are putative risk factors for the development of immune suppression-related and Epstein-Barr virus-related lymphomas, the vast majority of lymphomas in this setting are of B-cell origin, and rarely are these primary cutaneous in nature. In addition, our patient's tumor displayed an unusual phenotype, with immunophenotypic features suggestive of an atypical natural killer-/T-cell lymphoma. Methotrexate was withdrawn, and our patient was successfully treated with local radiotherapy. She has remained in complete remission 28 months since diagnosis.

The histopathology of noncicatricial alopecia.

During the past 2 decades, the use of transverse sections in the evaluation of scalp biopsy specimens has led to a better understanding of the histopathologic changes in both cicatricial and noncicatricial alopecia. However, the technique has provided the most significant gains in the study of the latter type of alopecia, where evaluation of follicle density and follicular dynamics are integral to accurate diagnosis. This report reviews the histopathologic findings of four common types of noncicatricial alopecia: androgenetic alopecia, telogen effluvium, alopecia areata, and trichotillomania/chronic traction alopecia.

Paraganglioma-like dermal melanocytic tumor: a unique entity distinct from cellular blue nevus, clear cell sarcoma, and cutaneous melanoma.

We are reporting a previously undescribed primary dermal melanocytic tumor identified by reviewing all dermal melanocytic tumors referred in consultation that did not qualify histologically as a previously described entity. From these cases, 8 were remarkably similar. We termed them "paraganglioma-like dermal melanocytic tumor" (PDMT) based on their nested growth pattern. This term is used descriptively and does not imply any histogenetic or biologic similarity to true paraganglioma. PDMT is primarily a tumor of the extremities of adult females (18-53 years, mean 35 years; males 2; females 6) which present as a dermal nodule (range, 0.5-4.2 cm; mean, 1.4 cm) composed of nests of clear to amphophilic oval cells separated by delicate fibrous strands. Nuclear atypia was mild and mitotic activity low (1-4 mitoses/10 HPF). Melanin was not obvious on light microscopy. Tumors expressed S-100 protein (8 of 8), Melan-A (4 of 8), HMB-45 (8 of 8), and microphthalmia transcription factor (8 of 8) and lacked pancytokeratin (8 of 8) and smooth muscle actin (8 of 8). FISH analysis of 5 cases revealed an intact EWS gene locus, supporting absence of the clear cell sarcoma 12;22 translocation. Follow-up information in 8 patients (range, 35-92 months; mean, 54 months) indicated that all were alive without disease. PDMT comprises a clinically and pathologically unique subtype of dermal melanocytic tumors. Our study suggests a benign course, although a lesion of low malignant potential cannot be excluded.

The role of calcitonin gene-related peptide in cutaneous immunosuppression induced by repeated subinflammatory ultraviolet irradiation exposure.

Ultraviolet (UV) light is an effective treatment for skin disorders like psoriasis in which the cutaneous neurosensory system may have a pathogenic role. In this study, we examined the possibility that UV modulation of the cutaneous neurosensory system and calcitonin gene-related peptide (CGRP) may contribute to local immunosuppression mediated by repeated subinflammatory UV irradiation. Our results indicated that exposure of hairless mice to subinflammatory UV three times weekly for 4 weeks significantly increased the number of epidermal nerve fibers (ENFs) immunoreactive for CGRP without altering the total number of ENFs. The skin content of CGRP as measured by enzyme-linked immunosorbent assay was also significantly increased after exposure to this dose of UV. These effects were most apparent 1 day after the last UV exposure and declined 1 week after UV. The role of CGRP in UV-induced immunosuppression of contact hypersensitivity was then examined. Our results indicated that UV suppression of epicutaneous 2,4-dinitro-1-fluorobenzene (DNFB) sensitization could be significantly inhibited by a systemically administered CGRP receptor antagonist. A broad-spectrum sunscreen applied before UV exposure inhibited increased cutaneous CGRP and blocked immunosuppression. These findings support a role for CGRP in the local immunosuppression caused by chronic, repeated subinflammatory UV exposure.

Proliferating trichilemmal tumors: clinicopathologic evaluation is a guide to biologic behavior.

BACKGROUND: Trichilemmal (pilar) cysts are common skin lesions that usually occur on the scalp of elderly women. They differentiate towards the follicular outer root sheath epithelium and show trichilemmal keratinization. Proliferating trichilemmal tumor (PTT) shows features of typical pilar cyst, but additionally shows extensive epithelial proliferation, variable cytologic atypia and mitotic activity. The malignant potential of PTT is controversial, as only a small number of histologically malignant PTTs and a smaller number of clinically malignant PTTs have been reported. METHODS: We retrieved from our archives five PTTs that deviated from ordinary PTTs with regards to either cytology or architecture. We also reviewed all previous reports of histologically malignant PTTs, with the goal of delineating criteria for the diagnosis of malignant PTTs. RESULTS: Five cases of PTT showing atypical cytoarchitectural features were retrieved from our archives and reviewed with respect to size, growth pattern, cellularity, cytologic atypia, and mitotic activity. The patients (four female, one male) ranged from 54 to 83 (mean 65) years. The tumors measured from 1 to 16 cm in diameter (mean 5 cm) and four out of five occurred on the scalp. All tumors showed at least focal areas of typical PTTs. Three cases were circumscribed but had areas of moderate to focally marked cytologic atypia. Two cases showed infiltrative growth, marked cytologic atypia and mitotic activity. Clinical follow-up was available for four of five cases and ranged from 6 to 84 (median 48) months. Follow-up showed two cases with local recurrence and one case with distant metastasis. This last patient died of disease; all other patients are disease-free. CONCLUSIONS: Review of our cases and the published literature suggests that the diagnosis of malignant PTT be given to PTT showing a combination of non-scalp location, recent rapid growth, size greater than 5 cm, infiltrative growth, and significant cytologic atypia with mitotic activity. At the present time the stratification of malignant PTT into low- and high-grade categories is not possible.

Acral lentiginous melanoma mimicking benign disease: the Emory experience.

BACKGROUND: Plantar and subungual melanoma exhibits a higher misdiagnosis rate relative to other anatomic sites. Misdiagnosis and delay in diagnosis are statistically associated with poorer patient outcome. Awareness of atypical presentations of acral melanoma may, thus, be important to decrease misdiagnosis rates and improve patient outcome. METHODS: We conducted a retrospective case review of plantar or lower-extremity subungual melanoma performed at Winship Cancer Center, a tertiary care, referral center affiliated with Emory University, between 1985 and 2001. RESULTS: A total of 53 cases of plantar or lower-extremity subungual melanoma were identified. Of 53 cases with a final diagnosis of melanoma, 18 were initially misdiagnosed. Misdiagnoses included wart, callous, fungal disorder, foreign body, crusty lesion, sweat gland condition, blister, nonhealing wound, mole, keratoacanthoma, subungual hematoma, onychomycosis, ingrown toenail, and defective/infected toenail. Of the 18 misdiagnosed cases, 9 were clinically amelanotic. CONCLUSION: Awareness that amelanotic variants of acral melanoma may assume the morphology of benign hyperkeratotic dermatoses may increase the rate of correct diagnosis and improve patient outcome.