ALK-rearranged, CD34-positive spindle cell neoplasms resembling dermatofibrosarcoma protuberans: a study of seven cases.

AIMS: The majority of dermatofibrosarcoma protuberans (DFSP) harbour PDGFB or PDGFD rearrangements. We encountered ALK expression/rearrangement in a PDGFB/D-negative CD34-positive spindle cell neoplasm with features similar to DFSP, prompting evaluation of ALK-rearrangements in DFSP and plaque-like CD34-positive dermal fibroma (P-LDF). METHODS AND RESULTS: We searched the archives of academic institutions for cases previously coded as DFSP and P-LDF. NGS-naïve or PDGFB-negative DFSP were screened for ALK (clone D5F3) expression by immunohistochemistry. NGS or ALK FISH was performed on ALK-positive cases. Methylome profiling studies were performed and compared with conventional DFSP. One case of "DFSP" and two "P-LDF" with ALK expression were identified from the archives, while four cases were detected prospectively. These seven cases (6F:1M; 8 months to 76 years) arose in the dermis of the arm (two), scalp, eyelid, thigh, abdomen, and shoulder and ranged from 0.4 to 4.2 cm. Tumours were composed of spindled cells and displayed a storiform growth pattern. Cytologic atypia was absent, and mitotic figures were scarce (0-2/10 HPFs, high power fields). The lesional cells were diffusely positive for CD34 and ALK and negative for S100 protein. By NGS (n = 5), ALK fusion partners included DCTN1 (2), PLEKHH2, and CLIP2 in DFSP-like cases and FLNA in P-LDF-like lesions. ALK FISH was positive in one (of two) cases previously labelled P-LDF. Methylome profiling of two (of three) ALK-rearranged DFSP-like tumours showed clustering with conventional DFSP in the UMAP dimension reduction plot. To date, no tumour has recurred (n = 2; 26, 27 months). CONCLUSION: We describe a cohort of novel ALK-rearranged tumours with morphologic features similar to DFSP.

Cutaneous crystal storing histiocytosis: A case series with review of literature.

Crystal-storing histiocytosis (CSH) is a rare condition in which crystals accumulate in the cytoplasm of histiocytes and is usually associated with a lymphoplasmacytic neoplasm. Cutaneous CSH is extraordinarily rare and limited to case reports in the literature. We report two cases of this disease with cutaneous involvement. Case 1 was a 65-year-old male with a 4-month history of a pruritic eruption that started as a solitary pink to skin-colored indurated plaque on the anterior neck before progressing to involve the whole neck, chest wall, and face. Case 2 was a 54-year-old woman with a history of unspecified "lymphoma" who presented with a soft nodule on the forearm. Biopsies from both cases had similar findings and showed a proliferation of epithelioid cells with pink cytoplasm and intracellular crystalline structures infiltrating the dermis and subcutaneous fat. In the first case, the cells were positive for CD43, CD45, CD68, and IgG kappa, and in the second case, the crystals were positive for IgG lambda. Based on these findings, the patients were diagnosed with cutaneous CSH. We highlight this rare diagnosis and the importance of investigating an underlying lymphoplasmacytic neoplasm.

Marginal corneal infiltrates as an ocular manifestation of acute generalized exanthematous pustulosis.

Purpose: To report a case of keratoconjunctivitis with marginal corneal infiltrates in a patient with acute generalized exanthematous pustulosis (AGEP) secondary to trimethoprim-sulfamethoxazole. Observations: A 63-year-old female presented with a diffuse pustular skin rash and bilateral keratoconjunctivitis with marginal corneal infiltrates. Skin biopsy led to the diagnosis of AGEP secondary to trimethoprim-sulfamethoxazole use. Treatment of the ocular findings with topical corticosteroids and lubrication led to near-full resolution after two weeks. Conclusions and Importance: To the best of our knowledge, this is the first reported association between AGEP and keratoconjunctivitis with marginal corneal infiltrates. A hypersensitivity reaction to a foreign antigen is implicated in the pathogenesis of both AGEP and sterile marginal infiltrates, and we suggest that the patient's underlying hypersensitivity process associated with AGEP accounted for the ocular findings.

Novel Diagnostic Educational Resource: Use of a web-based adaptive learning module to teach inflammatory reaction patterns in dermatopathology to medical students, residents, and fellows.

Background: Perceptual and adaptive learning modules (PALM's) provide a large number of visual examples for evaluation and accommodate to learner performance by actively adjusting the module parameters. Methods: We developed a module for discriminating 5 inflammatory reaction patterns using the Novel Diagnostic Educational Resource (NDER) platform. The module included a 20 question pre-test, a 200 question training section, and a 20 question post-test. During the pre-test and post-test, images were displayed for an indefinite period of time with no feedback given. In the training section, images were displayed for a duration inverse to learner performance, and after submitting their response learners were immediately shown the correct answer. The performance of module participants was compared to a control group who completed pre-test and post-test only. Results: 26 pathology and dermatology residents completed the module and were included in analysis. Pre-test and post-test scores showed an average increase of 17.1 percentage points (95% CI 13.0 to 21.2, P < 0.001). When performance on pre-test and post-test was compared between the module and control groups, module group performance increased more than control group performance by an average of 10.1 percentage points (95% CI -2.5 to 17.8, P = 0.0119). 84% (37) of participants found the module somewhat useful or very useful and 68% (30) of participants would be pretty likely or very likely to recommend to another trainee. Conclusions: Our findings validate the use of NDER for teaching inflammatory reaction patterns. Participants generally had favorable feedback regarding the interface and teaching potential of the module. Including a late re-test as part of the module would be beneficial in further validating future iterations. Next steps include optimizing module performance and developing module content for more advanced learners.

Blastic plasmacytoid dendritic cell neoplasm presenting as violaceous forehead plaque.

A 72-year-old man with a history of squamous cell carcinoma presented to the Portland VA with forehead discoloration. He was initially diagnosed with actinic damage and prescribed topical treatment. However, he returned to clinic months later with a large, violaceous forehead plaque. Upon biopsy, he was diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare hematological malignancy. This case report illustrates the importance of keeping BPDCN in the differential diagnosis for ecchymotic plaques that fail to respond to first line therapy.

Dual treatment of cutaneous leishmaniasis with topical amphotericin B and photodynamic therapy in a pediatric patient.

Cutaneous leishmaniasis is a parasitic infection that can result in scarring, contributing to significant morbidity when a cosmetically sensitive area is involved. We report a case of a 13-year-old boy with cutaneous leishmaniasis involving the face and arm. He was treated with a combination of photodynamic therapy as well as topical amphotericin with a cosmetically satisfying outcome. This combination of noninvasive treatment regimens has not been reported to our knowledge and merits further study in the pediatric population.

A Case of Tofacitinib-Induced Lymphomatoid Papulosis With Ocular Involvement.

ABSTRACT: Janus kinase (JAK) inhibitors are being prescribed with increasing regularity in dermatology. We report on a patient who initiated treatment with tofacitinib for refractory erythema elevatum diutinum and subsequently developed a novel cutaneous outbreak characterized by firm violaceous papules on the trunk and extremities along with conjunctival injection and periorbital inflammation. Biopsy of affected tissue from both the cutaneous and ophthalmologic sources demonstrated increased numbers of CD30+ large atypical cells amid a mixed inflammatory cell infiltrate, consistent with lymphomatoid papulosis. A review of the literature reveals a plausible mechanism for the induction of persistent JAK signaling in the presence of a JAK inhibitor. We discuss this mechanism in depth because it pertains to this patient and recommend continued vigilance with the use of these immunologic agents.