Atypical Spitz tumor with SQSTM1::NTRK2 fusion: Report of a case with unique spindled cell features.

A host of signature genetic alterations have been demonstrated in Spitz neoplasms, most notably fusions of kinase genes (including BRAF, ALK, ROS1, NTRK1, NTRK3, RET, MET, MAP3K8) or variants in HRAS. While there are multiple reports of rearrangements involving NTRK1 and NTRK3 in Spitz tumors, there are very few reports of NTRK2-rearranged Spitz nevi in the literature. This report presents an NTRK2-rearranged atypical Spitz tumor with spindled cell features. The patient was a 6-year-old female with a growing pigmented papule on the back. Histopathological evaluation revealed an asymmetric, biphasic, compound proliferation of melanocytes featuring an epithelioid cell population arranged as variably sized nests and single cells along the basal layer with extension down adnexa, as well as a population of spindled melanocytes with desmoplastic features and loss of Melan-A expression in the dermis. There was partial loss of p16 expression in the epidermal component and diffuse loss in the dermal component. Immunohistochemistry for PRAME, ALK, NTRK1, HRAS Q61R, p53, and BRAF V600E were negative. A SQSTM1::NTRK2 fusion was identified by RNA sequencing. No TERT promoter hotspot variants were detected. This case report expands the known histopathologic spectrum of genetic alterations in Spitz neoplasms.

Eosinophilic Annular Erythema Responding to Doxycycline.

Eosinophilic annular erythema (EAE) is a rare skin disease characterized by relapsing and remitting pruritic, annular erythematous plaques and tissue eosinophilia. A 39-year-old male presented with a mildly pruritic, relapsing, and remitting urticarial rash. A biopsy revealed superficial and deep perivascular dermatitis with numerous eosinophils and some neutrophils, with an absence of flame figures. Based on clinical and histopathologic findings, the patient was given a diagnosis of eosinophilic annular erythema. Treatment was initiated with doxycycline 100 mg twice daily. The patient reported substantial improvement at three months and sustained clearance at one year, remaining on doxycycline well tolerated throughout. To our knowledge, no cases of EAE improving with doxycycline have been reported in the literature and, thus, our findings highlight a potential new therapy to consider in a patient with EAE.

Nonsebaceous lymphadenoma arising as a painless subcutaneous nodule on the eyebrow.

Salivary gland tumors can rarely present in skin excision specimens and can pose a diagnostic challenge to dermatopathologists. We present an exceptional case of a salivary gland type nonsebaceous lymphadenoma presenting as a painless subcutaneous nodule on the right medial eyebrow of a 16-year-old male, mimicking a primary cutaneous adnexal neoplasm. Histologic evaluation revealed a well-circumscribed to partially encapsulated nodule with a marked lymphoid infiltrate including reactive germinal centers. Within the lymphoid component was a central epithelial cystic neoplasm with tubuloglandular and basaloid differentiation. There was no myoepithelial component to suggest a chondroid syringoma. No sebaceous differentiation was present. The overall histopathological and immunohistochemical findings were consistent with a nonsebaceous lymphadenoma. Dermatopathologists should consider salivary gland type lymphadenoma as a differential diagnosis when encountering a subcutaneous lesion with lymphoid, cystic, glandular, and basaloid components.

Expression of p40 in Primary Cutaneous Mucinous Carcinoma Versus Primary Mucinous Carcinomas of the Breast and Colon.

BACKGROUND: The transcription factor p63 is a homolog of p53, expressed in basal layers of epithelia and myoepithelial cells. Some studies have suggested that p63 may provide utility in differentiating primary versus metastatic mucinous carcinoma of the skin, given its preferential expression in primary adnexal neoplasms. There have been few studies investigating the expression patterns of p40, an isoform of p63, in primary cutaneous mucinous carcinomas. METHODS: An immunohistochemical panel including p40, CK7, CK20, estrogen receptor, and progesterone receptor was applied to primary mucinous carcinomas of the skin, breast, and colon. RESULTS: Only a small subset (25%) of primary cutaneous mucinous carcinomas displayed focal positive staining with p40, similar to what has been reported in the literature for p63. All primary mucinous carcinomas of skin and breast labeled positively with CK7, estrogen receptor, and progesterone receptor. Primary colon mucinous carcinomas were only positive for CK20. CONCLUSIONS: Based on these results, p40 seems to be an insufficient marker for distinguishing primary versus metastatic mucinous carcinoma due to its low rate of positivity in primary cutaneous mucinous carcinomas.

Generalized Multinucleate Cell Angiohistiocytoma: Histopathological and Immunohistochemical Analyses of 10 Lesions.

ABSTRACT: Multinucleate cell angiohistiocytoma (MCAH) is an uncommon fibrohistiocytic disorder that usually presents as a localized solitary papule or multiple grouped papules. Generalized presentation is very rare with less than 20 cases reported in the literature. In this article, we present histopathological and immunohistochemical studies of 10 lesions from a patient with generalized MCAH. In all lesions, the histopathological changes were confined to a discrete zone of the superficial dermis that consisted of (1) an increase in the number of capillary-sized vessels with thickened walls, (2) presence of oval to dendritic spindle cells and stellate hyperchromatic multinucleated cells, (3) fibrosis marked by compact collagen, (4) hypertrophy and hyperplasia of small nerve fibers, and (5) a moderately dense lymphocytic infiltrate. The entire population of the cellular component including the multinucleated cells stained for CD10, whereas a subpopulation of the mononuclear spindle cells stained for factor XIIIa and CD68. CD34 highlighted only the blood vessels. The results confirm that the multinucleated cells lack expression of CD68 and factor XIIIa and that CD10 may be used to highlight the entire cellular component. The rarely reported hypertrophy and hyperplasia of nerve fibers in MCAH may be a common finding as it was observed in all 10 lesions.

Evolution of a melanoma in situ to a sarcomatoid dedifferentiated melanoma.

Sarcomatoid dedifferentiated melanoma (SDDM) is a recently recognized subtype of melanoma that stains diffusely for CD10 and lacks the expression of the usual melanocytic markers including S100, SOX10, MITF, and Melan A. Advances in next-generation DNA sequencing technology have facilitated the increased recognition of this rare, aggressive spindle cell melanoma. Herein, a case of relatively early lesion of SDDM arising in association with melanoma in situ is highlighted. A 72-year-old man with a history of previously treated melanoma in situ on the face five years prior presented with a new rapidly growing lesion within the scar of the treated site. A shave biopsy of the lesion revealed a centrally located 1.8-mm deep, poorly differentiated spindle cell neoplasm in association with an adjacent recurrent melanoma in situ. The spindle cell component stained diffusely for CD10, but failed to stain for S100, SOX10, and Melan-A while the melanoma in situ expressed all three melanocytic markers. Next-generation DNA sequencing assay revealed mutations in NF1, CDKN2A, TP53, and TSC1. A diagnosis of stage 2B SDDM arising in association with melanoma in situ was established based on the clinical context and genomic assay results.

Clinical and histopathological features of pagetoid Spitz nevi of the thigh.

BACKGROUND: Pagetoid Spitz nevus is a rare subtype of Spitz nevus usually found on the lower extremities, particularly on the thigh of women. As a rare and under-recognized entity that can be misdiagnosed as melanoma, further characterization of clinical and histopathological features is needed to improve its recognition. METHODS: A retrospective analysis of all melanocytic neoplasms from the thigh diagnosed over a 3-year period. RESULTS: Fifty-five (15.4%) of the 357 melanocytic neoplasms on the thigh were Spitz nevi, the majority of them occurring in women (87.3%). Of the 55 Spitz nevi, 33 (60.0%) were pagetoid Spitz nevi, 14 (25.5%) were Reed nevi, and eight (14.5%) were conventional Spitz nevi. The mean age of patients with pagetoid Spitz nevi was 47.2, the majority being women (84.9%). Pagetoid Spitz nevi were small, with a mean histopathologic diameter of 4 mm, and often junctional (63.6%). Compared to Clark nevi of the thigh, pagetoid Spitz nevi comprised significantly more solitary melanocytes with a greater degree of scatter. CONCLUSIONS: These results suggest that Spitz nevi and, in particular, pagetoid Spitz nevi constitute a significant percentage of nevi on the thigh. Previously reported benign clinical and histopathological features of pagetoid Spitz nevi are confirmed in this study.

Characteristics of Nontuberculous Mycobacterial Infections at a Midwestern Tertiary Hospital: A Retrospective Study of 365 Patients.

BACKGROUND: The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease. METHODS: We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, clinical findings, treatment, and outcome was obtained from medical records of all NTM isolates. American Thoracic Society/Infectious Diseases Society of America criteria were used to define pulmonary NTM infections. RESULTS: We identified 1064 NTM isolates, 365 of which met criteria for NTM infection. Pulmonary cases predominated (185 of 365; 50.7%), followed by skin/soft tissue (56 of 365; 15.3%), disseminated (40 of 365; 11%), and lymphatic (28 of 365; 7.7%) disease. Mycobacterium avium complex was the most common species (184 of 365; 50.4%). Individuals aged >50 years were most affected (207 of 365; 56.7%). Common comorbidities included structural lung disease (116 of 365; 31.8%), use of immunosuppressive medications (78 of 365; 21.4%), malignancy (59 of 365; 16.2%), and human immunodeficiency virus (42 of 365; 11.5%). CONCLUSIONS: This large cohort provides information on the demographics, risk factors, and disease course of patients with pulmonary and extrapulmonary NTM infections. Most patients had medical comorbidities that resulted in anatomic, genetic, or immunologic risk factors for NTM infection. Further population-based studies and increased disease surveillance are warranted to further characterize NTM infection prevalence and trends.

Assessing factors affecting sunscreen use and barriers to compliance: a cross-sectional survey-based study.

While sunscreen is effective prevention for skin cancer, public sunscreen use and compliance are low. Identifying factors affecting sunscreen use and barriers to compliance are important to understand in order to increase sunscreen use, especially among high-risk individuals. We conducted a single institution survey of 429 dermatology clinic patients to better understand patients' barriers to sunscreen use. Overall several personal barriers to sunscreen use included dislike of feel or appearance of sunscreen (33.7%) and time constraints (15.3%). The cost was a barrier to use in 16.4% of cases underscoring the importance for dermatologists to consider socioeconomic barriers to sunscreen use and provide cost-effective sun protection counseling to patients whenever possible. Dermatologists recommending sunscreen use was associated with a higher rate of use of sunscreen (p < .001) highlighting the important role of sun protective counseling by the dermatologist.

Acute Flare of Bullous Pemphigus With Pembrolizumab Used for Treatment of Metastatic Urothelial Cancer.

In the past decade, the resurgence of immunotherapy has changed the landscape of cancer therapy. Checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen-4, programmed death-1 on lymphocytes, and programmed death ligand-1 on tumors cells are currently utilized in the management of several cancers. These agents are double-edged sword with the positive effect being robust antitumor response but on the other side they can throttle up the normal immunologic homeostasis in a negative way, leading to adverse autoimmune toxicities. These adverse toxicities are frequent if patients have active autoimmune disorders. Here, we report a rare case of quiescent bullous pemphigoid which flared after initiation of pembrolizumab, a programmed death ligand-1 inhibitor.

Racial differences in the use of extracorporeal photopheresis for mycosis fungoides.

BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment option for mycosis fungoides (MF) and associated with few systemic side effects. OBJECTIVE: We sought to investigate whether there were differences in rates of ECP use between African-American and Caucasian patients with stage III/IV MF. METHODS: We conducted a retrospective review of all patients treated for MF at the Johns Hopkins Hospital main campus outpatient clinic between 1999 and 2011. RESULTS: We identified 65 patients with stage III or IV disease, 20 African-American and 45 Caucasian. Only 7 of 20 African-American patients (35%) compared with 30 of 45 (66%) of Caucasian patients were treated with ECP (p = 0.029). In addition, ECP was discussed as an option for 45% of African-Americans compared to 82% of Caucasians (p = 0.007). When discussed as an option, African-Americans and Caucasians had identical rates of ECP use (78% vs 81%, p = 0.841). CONCLUSIONS: Differences in rates of ECP use exist among African-American patients when compared to their Caucasian counterparts and may be related to how often ECP is offered as a treatment option. Improving physician awareness of the factors that influence treatment decision making may help diminish discrepancies in treatment regimens among patients with MF.

Large cystic mass in the right atrium: multimodality imaging and pathologic features of a giant interatrial septal aneurysm.

The case demonstrates the use of echocardiography, cardiac computed tomography (CCT) and cardiac magnetic resonance imaging (CMRI) to determine the size, location, anatomic connection, perfusion and hemodynamic significance of a large tumor in the right atrium. The mass was surgically excised and pathology confirmed an ultimate diagnosis of an interatrial septal aneurysm (ISA). Transesophageal echocardiography enhances the sensitivity of detecting ISA and is the initial test of choice when an ISA is suspected on transthoracic echocardiography. In addition, the use of CCT and CMRI helps further define the anatomy, perfusion and tissue characteristics of the mass. Our case demonstrates the utility of multimodality non-invasive imaging to characterize an unusual tumor leading to a successful surgical treatment and a corresponding pathologic diagnosis of a large, cystic aneurysm of the interatrial septum.

Extensive cutaneous sarcoidosis and coexistant Crohn disease with dual response to infliximab: case report and review of the literature.

Sarcoidosis and Crohn disease (CD) are granulomatous disorders of unknown etiology that are rarely seen together in one patient. We describe a woman in her 40s with well-established diagnoses of pulmonary and cutaneous sarcoidosis and CD involving the terminal ileum, whose skin and gastrointestinal symptoms improved dramatically with infliximab treatment (5mg/kg on weeks 0, 2, 6, then every 8 weeks). The concurrence of sarcoidosis and CD has only been reported in a handful of cases and a review of the literature reveals that the two diseases share many clinical and immunological features, suggesting the presence of an underlying connection. Further studies of patients with overlap syndromes may provide deeper insight into the clinical spectrum, and possibly the pathogenesis, of idiopathic granulomatous diseases.