A. Husain

Cutaneous features of intravascular lymphoma

Intravascular lymphoma (IVL) is a subset of extranodal non‐Hodgkin lymphoma, with an estimated incidence of <u20031 case per million people. It is characterised by extensive proliferation of lymphoma cells within small to medium‐sized blood vessels. Most IVLs are B‐cell tumours. IVL can present primarily in any organ system, including the skin. The disease is often disseminated at diagnosis. The overall mortality rate is thought to be >u200380%, and >u200350% of patients are diagnosed at postmortem examination. There is wide variability in the clinical appearance of cutaneous lesions, which may simulate inflammatory skin disease. Therefore, awareness by dermatologists is important to enable early diagnosis when cutaneous signs are present. We report two patients with unexplained systemic disease and a skin eruption, leading to the diagnosis of IVL, and outline the range of cutaneous features reported.

Prospective study of formalin-fixed Mohs surgery and haematoxylin and eosin stains with control contralateral biopsies for lentigo maligna: 5-year follow-up results.

There is little consensus on the optimum form of surgical management for lentigo maligna (LM). Currently, because malignant melanocytes spread down adnexal structures, full‐thickness skin removal is the only surgical option. Interpretation of Mohs histological specimens is difficult because of the presence of abnormal melanocytes in otherwise normal sun‐damaged skin.

A case of metastatic non-neural granular cell tumor in a 13-year-old girl.

Conventional granular cell tumor represents a mesenchymal neoplasm observed in a variety of locations and is now believed to be of Schwann cell origin. Granular cell change has also been observed in a variety of different tumors, but recently described in the skin has been a distinct entity termed non‐neural granular cell tumor, which lacks expression of S100 protein and is of uncertain histogenesis. This tumor typically displays a greater degree of nuclear atypia and mitotic activity than conventional granular cell tumor but appears to behave in a relatively benign fashion, as only two previous instances of lymph node metastasis have been documented. Herein, we report a case of non‐neural granular cell tumor arising on the back of a 13‐year‐old girl, and later axillary lymph node metastasis with extracapsular extension was observed.

Inherited pulmonary cylindromas: Extending the phenotype of CYLD mutation carriers

Germline mutations in the tumour suppressor gene CYLD are recognized to be associated with the development of multiple cutaneous cylindromas. We encountered such a patient who presented with breathlessness because of multiple pulmonary cylindromas.

Desmoplastic melanoma presenting with localized hair repigmentation

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Acute generalized exanthematous pustulosis induced by a topical agent: 2-chlorobenzylidene malonitrile (CS) gas

1 Taibjee SM, Bennett DC, Moss C. Abnormal pigmentation in hypomelanosis of Ito and pigmentary mosaicism: the role of pigmentary genes. Br J Dermatol 2004; 151:269–82. 2 Hogeling M, Frieden IJ. Segmental pigmentation disorder. Br J Dermatol 2010; 162:1337–41. 3 Rieger E, Kofler R, Borkenstein M et al. Melanotic macules following Blaschko’s lines in McCune–Albright syndrome. Br J Dermatol 1994; 130:215–20. 4 Dumitrescu CE, Collins MT. McCune–Albright syndrome. Orphanet J Rare Dis 2008; 3:12.

Break a Sweat in the Diagnosis and Management of a Flesh-Colored Nodule

To the Editor: Eccrine porocarcinoma (EPC), which is a tumor of the sweat ducts, most commonly affects older adults, with an average age of 68, but may occur at any age. It may arise originally in malignant form but most often develops from a long-standing benign eccrine poroma as a form of degenerative progression. It is not uncommon for the lesion to be misdiagnosed. Because the tumor has the capacity to metastasize, with consequent poor prognosis, it is imperative for accurate diagnosis and management.

An incidental finding of an asymptomatic intraneural glomus tumor: A case report and review of the literature

Glomus tumors are rare, soft‐tissue neoplasms arising from the thermoregulatory neuromyoarterial glomus bodies. They are commonly observed in the extremities and typically present with symptoms of cold hypersensitivity, pain and localized tenderness. Intraneural glomus tumors (INGTs) are even rarer. Here we review the literature on INGT and present an unusual case of an asymptomatic INGT, found incidentally within the excision specimen of a spiradenocarcinoma that arose near the natal cleft. Interestingly, this had not been identified on magnetic resonance imaging (MRI) used to investigate the spiradenocarcinoma. Although glomus tumors are usually considered benign, malignant transformation has been reported, highlighting the need for reporting pathologists and treating clinicians to be aware of this entity.

Targeting Tropomyosin Receptor Kinase in Cutaneous CYLD Defective Tumors With Pegcantratinib: The TRAC Randomized Clinical Trial

Importance There are no medical interventions for the orphan disease CYLD cutaneous syndrome (CCS). Transcriptomic profiling of CCS skin tumors previously highlighted tropomyosin receptor kinases (TRKs) as candidate therapeutic targets. Objective To investigate if topical targeting of TRK with an existing topical TRK inhibitor, pegcantratinib, 0.5% (wt/wt), is safe and efficacious in CCS. Design, Setting, and Participants A phase 1b open-label safety study, followed by a phase 2a within-patient randomized (by tumor), double-blind, placebo-controlled trial (the Tropomyosin Receptor Antagonism in Cylindromatosis [TRAC] trial). The setting was a single-center trial based at a tertiary dermatogenetics referral center for CCS (Royal Victoria Infirmary, Newcastle, United Kingdom). Patients who had germline mutations in CYLD or who satisfied clinical diagnostic criteria for CCS were recruited between March 1, 2015, and July 1, 2016. Interventions In phase 1b, patients with CCS applied pegcantratinib for 4 weeks to a single skin tumor. In phase 2a, allocation of tumors was to either receive active treatment on the right side and placebo on the left side (arm A) or active treatment on the left side and placebo on the right side (arm B). Patients were eligible if they had 10 small skin tumors, with 5 matched lesions on each body side; patients were randomized to receive active treatment (pegcantratinib) to one body side and placebo to the other side once daily for 12 weeks. Main Outcomes and Measures The primary outcome measure was the number of tumors meeting the criteria for response in a prespecified critical number of pegcantratinib-treated tumors. Secondary clinical outcome measures included an assessment for safety of application, pain in early tumors, and compliance with the trial protocol. Results In phase 1b, 8 female patients with a median age of 60 years (age range, 41-80 years) were recruited and completed the study. None of the participants experienced any adverse treatment site reactions. Three patients reported reduced pain in treated tumors. In phase 2a (15 patients [13 female; median age, 51 years], with 150 tumors), 2 tumors treated with pegcantratinib achieved the primary outcome measure of response compared with 6 tumors treated with placebo. The primary prespecified number of responses was not met. The incidence of adverse events was low. Conclusions and Relevance In this study, pegcantratinib, 0.5% (wt/wt), applied once daily appeared to be well tolerated and to penetrate the tumor tissue; however, the low tumor drug concentrations demonstrated are likely to account for the lack of response. Dose-escalation studies to assess the maximal tolerated dose may be beneficial in future studies of CCS. Trial Registration isrctn.org Identifier: ISRCTN75715723

Squamous cell carcinomas in linear epidermal naevi

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