Case Report: Infantile Urticaria as a Herald of Neonatal Onset Multisystem Inflammatory Disease With a Novel Mutation in NLRP3.

Neonatal multisystem onset inflammatory disorder (NOMID) is a severe autoinflammatory syndrome that can have an initial presentation as infantile urticaria. Thus, an immediate recognition of the clinical symptoms is essential for obtaining a genetic diagnosis and initiation of early therapies to prevent morbidity and mortality. Herein, we describe a neonate presenting with urticaria and systemic inflammation within hours after birth who developed arthropathy and neurologic findings. Pathologic evaluation of the skin revealed an infiltration of lymphocytes, eosinophils, and scattered neutrophils. Genetic analysis identified a novel heterozygous germline variant of unknown significance in the NLRP3 gene, causing the missense mutation M408T. Variants of unknown significance are common in genetic sequencing studies and are diagnostically challenging. Functional studies of the M408T variant demonstrated enhanced formation and activity of the NLRP3 inflammasome, with increased cleavage of the inflammatory cytokine IL-1ß. Upon initiation of IL-1 pathway blockade, the infant had a robust response and improvement in clinical and laboratory findings. Our experimental data support that this novel variant in NLRP3 is causal for this infant's diagnosis of NOMID. Rapid assessment of infantile urticaria with biopsy and genetic diagnosis led to early recognition and targeted anti-cytokine therapy. This observation expands the NOMID-causing variants in NLRP3 and underscores the role of genetic sequencing in rapidly identifying and treating autoinflammatory disease in infants. In addition, these findings highlight the importance of establishing the functional impact of variants of unknown significance, and the impact this knowledge may have on therapeutic decision making.

Clinical and Histopathologic Characteristics of Metastatic and Locally Advanced Cutaneous Basal Cell Carcinomas.

ABSTRACT: Locally advanced or metastatic basal cell carcinomas (laBCCs or mBCCs) are rare, with few case series providing information on their epidemiology. We aimed to describe the clinical and histologic features of locally advanced and metastatic basal cell carcinomas. Forty cases of laBCC or mBCC were identified by searching Vanderbilt's database from 1984 to January 2019. A retrospective chart review was performed. Pathology slides were available for 23 cases (13 mBCCs and 10 laBCCs). Twenty-one of 23 cases were Clark level IV or V, with a mean depth of invasion of >7 mm for both types. The mean mitotic rate was 4.4 mitoses/mm2 for laBCCs and 3.3 mitoses/mm2 for mBCCs. Ulceration was identified in 7 laBCC and 8 mBCC cases. Perineural invasion was present in 2 laBCC and 6 mBCC cases, with 3 mBCCs invading nerves >0.1 mm. Of 13 mBCC cases, histologic subtypes included infiltrative (n = 9), nodular (n = 7), morpheaform (n = 4), and superficial (n = 2), with multiple patterns present in some specimens. 10 of 13 patients with mBCC had local recurrence before metastasis. In summary, we identified several potential markers of high-risk BCC, including perineural invasion, deep invasion, elevated mitotic rate, and local recurrence of the primary tumor.

Cutaneous Metastases From a Cribriform Adenocarcinoma of the Minor Salivary Glands.

Cutaneous metastases from solid tumor malignancies often emanate from breast, gastrointestinal, and lung tumors. Adenocarcinomas from minor salivary gland cancers may involve the skin contiguously but rarely as metastatic deposits. Furthermore, these metastases are usually locoregional and not distal. Recently, an uncommon neoplasm termed cribriform adenocarcinoma of the minor salivary glands has been described, and although it often spreads to cervical lymph nodes, metastatic involvement of the skin has not been reported.

Pancreatic fat necrosis in a 10-year-old girl: A case report and review of the literature.

We report here a case of a young girl with pancreatitis and pancreatic fat necrosis (PFN). This condition is rare in the pediatric age group, and its etiopathogenesis is different from disease in adults. Whereas PFN in adults typically results from pancreatitis secondary to pancreatic duct obstruction, alcohol abuse, and pancreatic adenocarcinoma, in children it appears to arise in a setting of systemic disease, often involving a genetic disorder.

An atypical pleomorphic lipomatous tumor arising on the cheek.

Pathologists and dermatopathologists commonly encounter tumors with adipocyte differentiation. Most are of minimal clinical significance. Those exhibiting atypical spindle cell morphology have been reported but the terminology for such neoplasms is unsettled. Tumors with both spindle cell and pleomorphic morphology are rare, with equally unsettled descriptive nomenclature. Recently, a series of such tumors, termed atypical pleomorphic lipomatous tumor, has been published. They resided in the deep soft tissue or subcutis. To date, such a tumor has not been reported with dermal involvement.

In utero development of epidermolysis bullosa acquisita.

We report the case of an infant born with perioral vesicles that rapidly spread to involve his mouth and the majority of his body. Histopathology, immunofluorescence, and enzyme-linked immunohistochemistry assays confirmed a diagnosis of epidermolysis bullosa acquisita (EBA). His mother had no history of EBA, and serum indirect immunofluorescence was negative. The patient improved rapidly with local wound care and oral dapsone.

Levamisole-induced vasculopathy with gastric involvement in a cocaine user.

Reports of levamisole-induced vasculopathy (LIV) secondary to use of levamisole-contaminated cocaine largely have been limited to the skin. We report the case of a 35-year-old woman with painful purpuric lesions affecting the cheeks, nose, ears, arms, and legs of several days' duration. She recently had used crack cocaine. A biopsy of a lesion on the right arm demonstrated leukocytoclastic vasculitis. She also reported abdominal pain and gastric reflux of recent onset but denied any history of gastrointestinal tract disease. An upper gastrointestinal endoscopy was performed and demonstrated hemorrhagic erosions of the esophagus and stomach similar in appearance to the cutaneous lesions. Because dermatologists often are the specialists making the diagnosis of LIV, it is important they inform other involved clinicians that the skin may not be the sole repository of vascular insult.

Risk Factors for Basal Cell Carcinoma in Men Younger Than 40 Years: A Case-Control Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in the United States and is more prevalent in older populations. OBJECTIVE: The aim of this study was to investigate BCC risk factors in male patients younger than 40 years. MATERIALS AND METHODS: A consecutive series of male patients with pathology-proven BCC and younger than 40 years at time of diagnosis were retrospectively identified along with matched controls. Phone interviews were conducted using a structured questionnaire, and differences between patients with and without BCC were investigated. RESULTS: A total of 50 patients with BCC and 27 controls were included in this study. Compared with controls, patients with BCC worked outdoor jobs for longer lengths of time (43.2 vs 15.6 months; p = .04), were more likely to have a family history of skin cancer (66% vs 44%; p = .02), and were more likely to use sunscreen heavily after biopsy (p = .02). Patients with multiple BCCs (n = 20) were more likely to have a history of substantial recreational sun exposure (p = .01) than patients with solitary lesions (n = 30). CONCLUSION: The authors conclude that outdoor sun exposure in patients with underlying genetic susceptibility is the most likely mechanism of BCC formation in young male patients.

Cutaneous infection with Mycobacterium obuense.

This report describes the presence of cutaneous nodules and ulceration of the right leg of 1-year duration in an elderly woman. Prior biopsies had demonstrated dermal and subcutaneous granulomatous inflammation. Special stains for microorganisms and cultures were repeatedly negative. Polymerase chain reaction evaluation of the tissue block demonstrated the presence of Mycobacterium obuense.