Primary melanoma of the nipple: Report of 10 cases including coexistence with Paget's disease.

Primary melanoma of the nipple (PMN) is exceedingly rare, with only single cases reported to date. We identified 10 patients with PMN: 5 females, 5 males, median age 55.5 years (range 29-66) at diagnosis of melanoma in situ (4 cases) or invasive melanoma (6 cases, Breslow depth 0.2 mm to 3.5 mm). Follow-up was available for all 10 patients (median 19 months, range 1-183). Nine patients had no evidence of disease; one patient died of disease (13.5 months) after presenting with a nodal metastasis. One case was exceptional, because the patient presented with a pigmented lesion that histopathologically exhibited co-existence of melanoma in situ and Paget disease, a challenging differential diagnosis due to immunohistochemical pitfalls in distinction between melanoma in situ and the pigmented variant of mammary Paget disease. Here we report the second largest series of PMN including a case of PMN colliding with mammary Paget disease, to raise awareness of these rare malignancies.

Glass shards masquerading as calcifications in the breast: A case report.

Noniatrogenically acquired foreign bodies in the nipple-areola complex or breast skin are rare and can have variable imaging features, depending on the nature of the foreign material. We present the case of a 41-year-old female who had numerous apparent round and punctate calcifications in the right periareolar breast, predominantly within the skin. The biopsy showed multiple glass shards on a background of scar tissue. Further discussion with the patient confirmed that the glass shards were acquired during a motor vehicle accident several years earlier. We also review the types of foreign body material observed in the breast, the imaging appearance of glass foreign bodies in soft tissue, and methods of removal.

Eosinophils in metastatic melanoma.

The potential significance of tissue eosinophils melanomas is unknown. We strove to determine a potential association between the presence of tissue eosinophils and prognosis of patients with metastatic melanoma (MM). A retrospective electronic data base was queried to identify patients (age ≥18 years) evaluated January 1, 2011-October 1, 2022 (inclusive) at our multi-site medical center, who had metastatic melanoma and at least 1 biopsy of melanoma or a melanocytic nevus that was reported to show eosinophils. Patient demographics, histopathological tumor features, AJCC classification parameters, and peripheral blood eosinophilia (PBE) obtained during the patients' routine care were recorded. Seven patients met inclusion criteria had checkpoint inhibitor therapy for MM; 4/7 had prominent eosinophil infiltrates among their melanocytic nevi or/and melanomas, and all had absent or less than predicted tumor progression. In our small cohort of patients undergoing immunotherapy for metastatic melanoma, the presence of tissue eosinophils among nevi or melanomas was associated with a favorable response. While lymphocytes have been considered key in the host response to melanoma, the role of eosinophils may be underappreciated.

Iatrogenic Demodex folliculitis: A case report.

Demodex folliculorum is a commensal mite that inhabits the orifices of cutaneous pilosebaceous follicles. Overgrowth of these organisms can lead to Demodex folliculitis, which typically presents as papules and pustules predominantly involving the temples, cheeks, and occasionally the chest. We present a 51-year-old woman with iatrogenic Demodex folliculitis secondary to immunosuppressive treatment for an autoimmune connective tissue disease. Histopathological exam of a skin biopsy, which revealed follicular Demodex mites, confirmed the diagnosis. The eruption was treated with oral ivermectin and topical metronidazole gel, and the patient's immunosuppressive regimen was decreased, resulting in marked improvement in the eruption within 6 weeks and no worsening of her underlying autoimmune disorder. This case emphasizes the importance of considering Demodex folliculitis in the differential diagnosis of a new onset rash in the context of immunosuppressive treatment.

Continuous positive airway pressure device-associated nonhealing ulcer on the nasal dorsum: chondrodermatitis nodularis nasi.

With increasing use of positive airway pressure devices for disordered breathing during sleep, appreciation for potential associated side effects is essential. Chondrodermatitis nodularis nasi is a rare variant of chondrodermatitis nodularis chronic helicis that presents as a nonhealing erosion or ulcer on the nose and can occur in association with chronic use of positive airway pressure devices. We present a case of symptomatic chondrodermatitis nodularis nasi associated with continuous positive airway pressure use, fully responsive to treatment, and propose that this condition is highly underrecognized. Dermatology referral can assist in diagnosis, management, and exclusion of cutaneous malignancy. CITATION: Reinhart JP, Isaq NA, Peters MS, Vidal NY. Continuous positive airway pressure device-associated nonhealing ulcer on the nasal dorsum: chondrodermatitis nodularis nasi. J Clin Sleep Med. 2023;19(6):1157-1159.

Clinical and histopathological features of hypereosinophilic syndrome with cutaneous involvement: The Mayo Clinic Experience.

BACKGROUND: Hypereosinophilic syndrome (HES) encompasses a group of diseases with blood hypereosinophilia and eosinophil-mediated organ dysfunction. HES-associated skin abnormalities, termed cutaneous HES (cHES) here, may influence diagnosis of HES. We sought to better define clinical and histopathological features of cHES. METHODS: We retrospectively reviewed clinical records and cutaneous histopathology of adult patients with HES evaluated at our institution from 2007 to 2018. RESULTS: Forty-one percent (61/150) patients with HES had cHES. The most common clinical morphologies were urticarial (30%) and eczematous (26%). Skin specimens most often showed a spongiotic pattern (31%) with abundant inflammation (50%) including eosinophils (85%). Two specimens (8%) showed interstitial granulomatous dermatitis, and two specimens showed eosinophilic fasciitis (8%). Vasculitis was not identified in any specimen. Eighty-four percent of patients with cHES had ≥1 other organ system involved: pulmonary 41%, ENT 26%, and nervous 23%. Sixty percent (53/89) of non-cHES patients had at least two organ systems involved. Cardiac or gastrointestinal involvement was more common in non-cHES than cHES (p < 0.05). CONCLUSION: Our review confirms that there are no specific clinical or histopathological cHES patterns, but HES should be considered in patients who have eczematous or urticarial reactions of unknown etiology and persistent peripheral hypereosinophilia.

Dysplastic nevus part II: Dysplastic nevi: Molecular/genetic profiles and management.

Dermatologists frequently see patients with clinically atypical nevi and dermatopathologists interpret histologically dysplastic nevi on a near-daily basis, but there is great variability in the definition and management of such lesions. This part of the CME review focuses on information published since the previous comprehensive review (2012), with emphasis on molecular and genetic attributes of histologically dysplastic nevi and clinical management.

Dysplastic nevus part I: Historical perspective, classification, and epidemiology.

Since the late 1970s, the diagnosis and management of dysplastic nevi have been areas fraught with controversy in the fields of dermatology and dermatopathology. Diagnostic uncertainty and lack of standardized nomenclature continue to propagate confusion among clinicians, dermatopathologists, and patients. In part I of this CME review article, we summarize the historical context that gave rise to the debate surrounding dysplastic nevi and review key features for diagnosis, classification, and management, as well as epidemiology. We discuss essentials of clinical criteria, dermoscopic features, histopathologic features, and the diagnostic utility of total body photography and reflectance confocal microscopy in evaluating dysplastic nevi, with emphasis on information available since the last comprehensive review a decade ago.

Histopathology of autoimmune bullous dermatoses: what's new?

Autoimmune bullous dermatoses are characterized by the presence of tissue-bound and often circulating pathogenic autoantibodies targeting structural components of the skin and/or mucous membranes. The diagnostic workup for this heterogeneous group of disorders consists of a multi-step process, of which the light microscopic examination is a crucial component. This review is organized following a classification scheme that is based on two main histopathologic features, namely level of intraepithelial split and composition of the inflammatory infiltrate. Overall, we aim to place emphasis on the histopathologic clues that can assist pathologists in differential diagnosis and review the updates in the literature.

Impact of adding an IgG4 conjugate to routine direct immunofluorescence testing for subepithelial and intraepithelial autoimmune blistering disorders.

BACKGROUND: Certain autoimmune bullous dermatoses are mediated by autoantibodies of the IgG4 subclass. We determined the diagnostic impact of adding IgG4 to our conventional direct immunofluorescence (DIF) panel. METHODS: For all cases submitted to our referral laboratory for DIF over 1 month (n = 630), we performed IgG4 testing and collected consecutive biopsy specimens showing definite or indeterminate linear or cell-surface deposition of IgG, IgG4, and/or C3. On retrospective blinded review, we classified the pattern and whether the findings were definite, indeterminate, or negative. When present, substantial background staining was recorded. RESULTS: Seventy DIF specimens met the inclusion criteria. Of 22 (31.4%) specimens equivocal for linear or cell-surface deposition, 9 (40.9%) had definitive IgG4 findings, either linear (3 of 14 equivocal linear cases; 21.4%) or cell-surface (6 of 8 equivocal cell-surface cases; 75.0%). Background deposition was substantial in 14 cases (20.0%) for IgG but in none for C3 or IgG4. CONCLUSION: IgG4 allowed the classification of over 40% of DIF cases that were otherwise equivocal by IgG and C3. IgG4 staining showed lower levels of non-specific background staining than IgG or C3. IgG4 appears to contribute most value in cases with cell-surface deposition or with equivocal linear IgG deposition and negative C3 results.

Cutaneous eccrine inflammation and necrosis: review of inflammatory disorders affecting the eccrine apparatus including new associations.

Despite being frequently overlooked during the examination of histopathological sections, eccrine sweat glands can offer clues for diagnosing various skin conditions. They provide important functions and can lead to several diseases when inflamed or injured. This review article provides information regarding eccrine physiology as well as well-established and novel entities that occur in association with eccrine gland pathology.

Kaposi sarcoma misdiagnosed as granuloma annulare: A case of mistaken identity.

The microscopic features of patch stage Kaposi sarcoma (KS) and interstitial granuloma annulare (GA) may be difficult to differentiate, because both may exhibit a subtle "busy" dermis due to infiltration of spindled cells between collagen bundles. The clinical distinction is particularly challenging in human immunodeficiency virus (HIV)-affected individuals, as the incidence of GA appears to be greater in the HIV-infected population. KS is the most common neoplasm in this population. Despite the significant decrease in the incidence of KS since the advent of highly active antiretroviral therapy (HAART), KS tends to occur with late onset and indolent progression in patients with preserved immune function and minimal viral load. We present a 47-year-old homosexual HIV-positive man, under virologic and immunologic control on long-term HAART therapy, with a 5-year history of progressive red-brown patches and plaques on the legs, feet, hands, and trunk. Prior skin biopsy specimens were interpreted as interstitial GA. Histopathology on new skin biopsy specimens along with review specimens supported the diagnosis of plaque and patch stages of KS, respectively, supported by immunohistochemical expression of human herpes virus-8 (HHV-8). This case underscores the importance of maintaining a high suspicion for KS in progressive, treatment-recalcitrant skin lesions, particularly in HIV-infected individuals.

Histopathologic features of noninfectious granulomatous disorders involving the skin.

Granulomatous dermatoses may represent primary skin inflammation or can serve as the harbinger of a multitude of underlying systemic disorders or drug reactions. Taken together with clinical findings, the microscopic features from skin biopsy can allow recognition of various patterns and facilitate a precise diagnosis. Accurate classification of entities in this category of inflammatory dermatoses may prompt clinicians to investigate for underlying systemic problems, thereby allowing the pathologist to add considerable value in the care of affected patients. This review article categorizes clinical and microscopic features of common and uncommon causes of noninfectious dermal and subcutaneous granulomatous inflammation.

Baseline characteristics and long-term outcomes of eosinophilic fasciitis in 89 patients seen at a single center over 20 years.

AIM: Eosinophilic fasciitis (EF) is a rare, fibrosing disorder of skin and subcutaneous tissue. This study was undertaken to describe its clinical and laboratory features and identify prognostic factors associated with outcome. METHODS: We conducted a retrospective review of all EF patients evaluated at our institution from 1 January1997 to 30 December 2016. Kaplan-Meier methods were used to determine treatment response rates over time. Potential associations between baseline characteristics and complete response were examined using Cox models adjusted for age and sex. Time-dependent covariates were used to examine treatment effects. RESULTS: We identified 89 EF patients, with a female-to-male ratio of 1:1. Clinical features included groove sign in 26 (29%), peau d'orange/dimpling in 22 (25%), inflammatory arthritis in 9 (10%) and muscle weakness in 9 (10%). Aldolase was elevated in 11/36 (31%). Complete response rate was 60% (95% confidence interval [CI]: 35-75) at 3 years. Diagnostic delay was inversely associated with treatment response (hazards ratio: 0.84 per 1 month increase; 95% CI: 0.73-0.98). No baseline characteristics correlated with treatment response, but a trend toward positive association of elevated aldolase, hypergammaglobulinemia and presence of hematologic disorders was noted. Methotrexate was the most commonly used immunosuppressant in 79%, hydroxychloroquine in 45%, mycophenolate mofetil in 18% and azathioprine in 8%. No single immunosuppressant agent was associated with a superior response during treatment. CONCLUSIONS: EF is characterized by relatively high response rates. Consensus diagnostic criteria, standardized management algorithms, and large prospective multi-center cohorts are needed to develop an evidence-directed approach to this challenging condition.