Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor therapy: A spectrum of immune reactions from paraneoplastic pemphigus-like to Grover-like lesions.

Checkpoint inhibitors (CPIs) restore the function of effector immunocytes to target and destroy cancer cells. Immune-related adverse events (irAEs) are a consequence of immune reactivation, with unpredictable inflammatory response, loss of self-tolerance, and development of autoimmunity. Adverse events from CPIs that present as dermatologic toxicities have diverse clinical and histopathologic features. CPI-associated dermatologic toxicities may exhibit histopathologic features of lichenoid dermatitis, bullous pemphigoid, and granulomatous/sarcoid-like reactions. Suprabasal acantholytic dermatologic toxicities associated with CPIs are particularly rare but represent an emerging histopathologic pattern and include lichenoid dermatitis with suprabasal acantholysis/vesicle formation to Grover disease (transient acantholytic dermatosis). Here, we report two patients who developed suprabasal acantholytic dermatologic toxicities during CPI therapy. One patient exhibited a CPI-associated autoimmune blistering disease with paraneoplastic pemphigus (PNP)-like features restricted to histopathology and immunofluorescence, while the other patient had Grover-like lesions. A review of the literature revealed a spectrum of suprabasal acantholytic dermatologic toxicities associated CPIs that may present as lichenoid dermatitis with acantholysis/vesicle formation, Grover-like eruptions, and lesions with PNP-like features restricted to histopathology and immunofluorescence. It is important for clinicians and pathologists to recognize the types of dermatologic toxicities associated with CPIs to direct appropriate therapeutic strategies.

Papillary adnexal neoplasm (aggressive digital papillary adenocarcinoma) on the ankle of a 15-year-old girl: case report and review of literature from a pediatric perspective.

Digital papillary adenocarcinoma is a rare malignant tumor of the sweat glands, most commonly encountered in adult males. Only few pediatric cases have been reported, with an apparent predominance of females and none on the ankle. We report a case of a 15-year-old girl with a slowly growing, non-tender mass on the right ankle presenting with difficulty in walking; clinically believed to be a keloid. Excision of the mass revealed a glandular neoplasm with largely eccrine and focally apocrine differentiation. Histologic features do not reliably predict biologic behavior. Because of the existing confusion over the nomenclature, we propose that such tumors be called 'papillary adnexal neoplasms of distal extremities'.

A Large Pilar Sheath Acanthoma of the Cheek Successfully Treated With Surgical Excision.

This case report describes an atypically large pilar sheath acanthoma (PSA) presenting on a patient's cheek. Due to the bothersome nature of the lesion, the patient underwent surgical excision, with subsequent histopathological analysis confirming the diagnosis of an unusually large PSA. In addition to a definitive diagnosis, surgical excision provided symptomatic relief for the patient.

Cutaneous metastases of malignant melanoma: a clinicopathologic study of 192 cases with emphasis on the morphologic spectrum.

Metastatic melanoma represents one of the most common types of cutaneous metastases. In up to 5% of patients, metastatic melanoma can be the first manifestation of the disease. For the most part, the histologic diagnosis of metastatic melanoma poses little diagnostic difficulty; however, some metastases may adopt unusual or unfamiliar appearances mimicking other benign and malignant conditions. We present a study of 192 cases of cutaneous metastatic melanomas with special emphasis on their spectrum of morphologic features. The patients were 115 men and 77 women, 23-91 years of age (mean 57 years). Most tumors were located on the proximal legs, scalp, and arms and ranged from 0.8 to 3.0 cm. One hundred ten cases showed the classic morphologic appearance of melanoma (well-circumscribed epithelioid dermal/subcutaneous nodule), 82 cases showed unusual histologic appearances that mimicked other benign and malignant neoplasms. In 16 patients (8.3%), there was no evidence of primary melanoma and the cutaneous metastasis was the only manifestation of the disease. The histologic diagnosis of cutaneous metastatic melanoma can pose difficulties for diagnosis, especially in the face of an unknown primary neoplasm. Unusual features observed in this series included examples of cutaneous metastatic melanoma that closely simulated metastatic carcinoma, dermatofibroma, leiomyosarcoma, angiosarcoma, nevoid melanoma, halo nevus, blue nevi, and atypical fibroxanthoma. Several cases also showed rhabdoid, balloon cell, and alveolar features. Immunohistochemical stains plus careful clinical history helped to establish the correct diagnosis. Our series illustrates that the differential diagnosis of cutaneous metastatic melanoma can be broad and difficult. To the best of our knowledge, this is the largest series of cutaneous metastatic melanomas reported in the literature.

Cutaneous melanoma metastatic to the eyelid and periocular skin.

PURPOSE: To report the clinical and histopathologic features in 6 patients with cutaneous melanoma metastatic to the eyelid and periocular skin. METHODS: Clinical records and radiographic features of all consecutive patients treated by the principal investigator between January 2005 and October 2007 with the diagnosis of cutaneous melanoma metastatic to the eyelid and periocular skin. RESULTS: Six patients ranged in age from 26 to 84 years old (median, 55 years). Five patients had their metastatic lesion in the upper eyelid and 1 in the lower eyelid. The mean survival after the diagnosis of melanoma metastatic to the eyelid was 5.3 months. All patients had metastases at other sites detected prior to the diagnosis of the eyelid metastasis. The mean interval from initial primary tumor diagnosis to metastasis to the eyelid was 121 months. In all 6 patients, palliative surgical resection of the metastatic eyelid lesions was carried out. CONCLUSIONS: Melanoma metastatic to the eyelid is not uncommon in advanced stage cutaneous melanoma. Palliative surgical management of these metastatic lesions should be considered to improve the patient's quality of life.

Spitzoid melanoma in children: clinicopathological study and application of immunohistochemistry as an adjunct diagnostic tool.

INTRODUCTION: The term spitzoid melanoma (SM) is reserved for a rare group of tumors with striking resemblance to Spitz nevus, often developing in children diagnosed in retrospect after the development of metastases. OBJECTIVES: To determine the biological significance of SM and to analyze the effectiveness of adjuvant diagnostic techniques. MATERIALS AND METHODS: A retrospective, observational study of 38 cases of SM in patients younger than 18 years. Histological type, Clark level and Breslow thickness, radial and vertical growth phase, mitotic count/mm(2), ulceration, regression, vascular and perineural invasion, satellitosis, cytology and associated nevi were reviewed. An immunohistochemical analysis with HMB45 and Ki67 was performed in 10 cases. These features were correlated to patient's stage and outcome. RESULTS: Analysis of histological and immunohistochemical features should allow accurate diagnosis in most cases. Given the low mortality rate, no conclusions about the prognostic significance of histological parameters of the primary tumor could be established. CONCLUSION: We report the largest series of SM from a unique center. Although these patients may have a better prognosis than adults, some patients with SM develop metastasis and die, particularly after age 11 years. Therefore, we recommend using the same treatments as in adults.

Common variable immunodeficiency syndrome associated with epidermodysplasia verruciformis.

We report the association of common variable immunodeficiency syndrome with epidermodysplasia verruciformis (EV) manifesting as flat warts and squamous cell carcinomas in a 21-year-old Hispanic woman. Human papillomavirus (HPV) typing by polymerase chain reaction using an EV-HPV primer system, cloning, and sequencing detected HPV-8 and HPV-23 DNAs in the biopsy sample. Our case is the second reported case of common variable immunodeficiency syndrome associated with EV.

Mycosis fungoides with coccidioidomycosis.

Mycosis fungoides is an indolent, epidermotropic, cutaneous T-cell lymphoma of helper/memory T cells that presents as heterogeneous, papulosquamous patches, plaques, and tumors. We present a patient with mycosis fungoides and infection with Coccidioides immitis of the skin, which has not been previously reported.

Morbilliform drug reaction with histologic features of pustular dermatosis associated with bryostatin-1.

Bryostatin-1 is a new chemotherapeutic agent that inhibits protein kinase C. The most common side effect and the dose limiting toxicity is myalgia. The cutaneous side effects reported during the phase I and II trials were alopecia, mucositis, nonspecific "rash," "bronzing," and hyperpigmentation in sun exposed areas. No specific acute drug eruptions have been reported. We present the first reported case of a morbilliform drug eruption with histologic features of intraepidermal and subcorneal spongiotic pustules containing eosinophils secondary to bryostatin-1.

Ultrasound biomicroscopy for estimation of tumor thickness for conjunctival melanoma.

We assessed the feasibility of using high-frequency ultrasound biomicroscopy (UBM) in estimating thickness of conjunctival melanomas preoperatively. Three patients underwent UBM prior to excision of conjunctival melanoma between February 2003 and March 2006. Conjunctival tumor thickness was estimated via UBM in each case and compared with the estimated histopathologic tumor thickness (Breslow thickness). Patient 1 had an estimated thickness of 1.99 mm via UBM versus a Breslow thickness measurement of 1.5 mm based on the surgical specimen. Patient 2 had a UBM thickness measurement of 2.4 mm and a Breslow thickness of 2.23 mm based on the surgical specimen. In patient 3, both UBM thickness and Breslow thickness were 2.3 mm. The use of high-frequency UBM is feasible for the estimation of tumor thickness for conjunctival melanomas. UBM may serve as an additional diagnostic tool for estimating tumor thickness before surgical resection of conjunctival melanoma.

Giant basal cell carcinoma associated with human papillomaviruses infection.

Different criteria have been used to define giant basal cell carcinoma (BCC). However, the majority of tumors of 10 cm or greater in diameter have a characteristic clinical and histopathologic presentation. As a group, these tumors often show metastatic spread as opposed to all other BCCs that rarely metastasize. We present an additional patient with a giant BCC greater than 100 cm2. This tumor had a characteristic location and infiltrative growth pattern. Unusual features of this tumor included a lack of expression of BCL-2 with a greater proportion of cycling tumor cells expressing proliferation markers than conventional BCC, as well as expression of anogenital human papillomaviruses (HPV) subtypes with oncogenic potential. The association of HPV with BCCs has rarely been studied and may not be identical to HPV-induced genital squamous cell carcinomas. However, the findings in this patient suggest that HPV may play a role in the development of some chronic giant BCCs.