Myeloid neoplasm with histiocytosis and spleen tyrosine kinase fusion responds to fostamatinib.

Not available.

Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation.

BACKGROUND: Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. OBJECTIVE: To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. MATERIALS AND METHODS: In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. RESULTS: The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. CONCLUSION: Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

Low-Grade Hidradenocarcinoma of the Foot With Metastasis to a Lymph Node.

ABSTRACT: Hidradenocarcinoma (HAC) is a rare adnexal tumor associated with the potential for locoregional recurrence and systemic metastasis. The clinical appearance of HAC is nonspecific, frequently presenting as a solitary firm subcutaneous nodule or plaque on the head and neck region or distal extremities. These tumors show histomorphologic heterogeneity, as they can be low and high grade. Distinguishing HAC from hidradenoma, especially the low-grade variant of HAC, can be challenging as both tumors can show histologic overlapping features. In this article, we describe a case of a 33-year-old patient presenting with a low-grade HAC of the plantar foot who was subsequently found to have lymph node metastasis.

Talimogene laherparepvec pseudolymphomatous reaction mimicking metastatic melanoma.

Talimogene laherparepvec (TVEC) is a genetically modified herpes simplex virus-1 approved as an intralesional oncolytic immunotherapy for the treatment of advanced melanoma. Cutaneous reactions at the site of injection may mimic recurrent or progressive melanoma; histopathological findings have included chronic granulomatous dermatitis, neutrophilic dermatitis, lymphocytic dermatitis, and pigment incontinence. We report a 39-year-old male with metastatic stage IIIc melanoma treated with TVEC with clinical regression of melanoma lesions that later developed pink nodules at sites of prior injection. Histopathology demonstrated a nodular mononuclear infiltrate that stained strongly and diffusely with CD45 and CD20 with a surrounding rim of CD3-positive T-cells. Immunoglobulin gene rearrangement was negative for a clonal B-cell population. To our knowledge, this is the first report of a pseudolymphomatous reaction mimicking recurrent melanoma after TVEC therapy.

Anogenital syringocystadenocarcinoma papilliferum in situ or anaplastic extramammary Paget disease? A unifying concept and review of the literature.

Extramammary Paget disease (EMPD) is a rare cutaneous malignancy that typically involves the genital skin and can be primary or associated with an underlying internal malignancy. The typical histopathological appearance of EMPD consists of single or small aggregates of cells with abundant pale cytoplasm and large pleomorphic nuclei, known as Paget cells, scattered throughout the epidermis. We report a case of anogenital EMPD occurring in a 53-year-old man with unusual histopathologic findings of marked epidermal acanthosis, acantholysis, intraepidermal glandular differentiation, and prominent plasma cell-rich fibrovascular cores. These features were entirely confined to the epidermis and adnexa with no evidence of dermal invasion or underlying systemic disease. We review and summarize the literature for atypical features noted in EMPD and summarize similar findings previously described under a variety of descriptions including anaplastic EMPD, anogenital syringocystadenocarcinoma papilliferum in situ (SCACPIS), SCACPIS-like changes in EMPD, and EMPD mimicking acantholytic squamous cell carcinoma in situ. We propose that these features represent a single entity and be considered under a unifying diagnosis to facilitate recognition of this entity.

GATA-3 expression in a de-differentiated chondrosarcoma with cutaneous iatrogenic implantation: a diagnostic pitfall with important clinical implications.

De-differentiated chondrosarcoma (DDCS) is an extremely aggressive tumor of the bone characterized by a high-grade, non-chondroid sarcoma adjacent to a low- or intermediate-grade chondrosarcoma. Adequate tumor sampling demonstrating the biphasic features is necessary to make an accurate diagnosis. The diagnosis may be challenging as histopathology may mimic other neoplasms. We present a case of a 76-year-old woman with a history of breast cancer who presented with a pathologic non-displaced fracture. A bone biopsy demonstrated a high-grade neoplasm composed of pleomorphic spindled and epithelioid cells with focal expression of AE1/3 and GATA3, most likely consistent with metastatic breast carcinoma. After a difficult clinical course, the tumor was resected demonstrating a similar morphology to her prior biopsy, as well as an area of a low-grade cartilaginous neoplasm consistent with chondrosarcoma. The biphasic tumor alongside a low-grade chondrosarcoma allowed for a diagnosis of DDCS. Several days after her procedure, the patient developed violaceous nodules overlying and surrounding the surgical site. Skin biopsy demonstrated a malignant epithelioid neoplasm with identical histomorphologic features identical to her prior bone resection. Given the location of the skin lesions directly within the surgical site right after resection, the clinical-pathological picture was that of sarcomatosis cutis by iatrogenic cutaneous implantation.

Evolution of Fibroblastic Connective Tissue Nevus in an Infant.

Fibroblastic connective tissue nevus (FCTN) is a rare and recently described neoplasm of fibroblastic/myofibroblastic lineage. We report a case of a 1-month-old healthy male infant who presented with a dermal plaque on the upper chest since birth. A punch biopsy demonstrated a dermal spindle-cell neoplasm with variable smooth muscle actin positivity and negative staining for CD34, consistent with myofibroma. Over the course of the next year, the remaining lesional tissue exhibited clinical softening and a surgical excisional specimen revealed histologic findings distinct from the original biopsy. These included a poorly circumscribed proliferation of bland spindle cells arranged in short fascicles centered in the dermis and extending into the subcutis with positivity for CD34, and absence of staining with smooth muscle actin features diagnostic of FCTN. Our case allowed the opportunity to see this unusual neoplasm at different stages, and we hypothesize that FCTN may undergo an early cellular phase and that time is required for these lesions to "mature" and demonstrate the more characteristic features of FCTN.

Lichen amyloidosis of the scalp and forehead.

Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis (PLCA), which presents as discrete, firm, closely-set 1-3mm, dome-shapedbrown papules commonly involving the anterior aspect of shins and extensor surfaces of forearms. We present a case of an otherwise healthy man in his 30s with solitary facial involvement of lichen amyloidosis, which is very uncommon.

Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation.

BACKGROUND: Disease-specific skin lesions are rare in patients with multiple myeloma (MM). OBJECTIVE: We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. METHODS: We identified 13 patients with cutaneous lesions of MM. RESULTS: Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. LIMITATIONS: The study group was relatively small. CONCLUSIONS: Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival.

Lentigo Maligna Melanoma With Local and Distant Blue Nevus-like Metastases.

Melanoma or melanoma metastases can rarely mimic blue nevi clinically and/or histologically, presenting a diagnostic pitfall for both the clinician and the dermatopathologist. We report a case of an invasive lentigo maligna melanoma with subsequent development of multiple, cutaneous blue nevus-like localized metastases followed by a distant metastasis, heralding widespread systemic metastases.

Graduate medical education success coaching for residents and fellows: a single-institution real-world experience.

While coaching has been employed as a success strategy in many areas such as athletics and business for decades, its use is relatively new in the medical field despite evidence of its benefits. Implementation and engagement regarding coaching in graduate medical education (GME) for residents and fellows is particularly scarce. We report our three-year experience of a GME success coaching program that aims to help trainees reach their full potential by addressing various areas of medical knowledge, clinical skills, efficiency, interpersonal skills and communication, professionalism, and mental health and well-being. The majority of participants (87%) were identified by themselves, their program director, and/or the GME coaches to have more than one area of need. The majority (79%) of referrals were identified by the coaches to have additional needs to the reasons for referral. We provide a framework for implementation of a GME coaching program and propose that coaching in GME may provide an additional safe environment for learners to reveal areas of concerns or difficulty that otherwise would not be disclosed and/or addressed.

Symmetrical drug-related intertriginous and flexural exanthema with high-risk systemic features: a unique clinical phenotype in hospitalized patients.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is classically considered a low-risk, self-limiting eruption lacking systemic manifestations and sparing facial and mucosal areas. We present 7 inpatients meeting diagnostic criteria for SDRIFE with concomitant systemic manifestations ± high-risk facial involvement acutely after antibiotic exposure (mean latency 6.71 days). These cases deviate from classic, self-limited SDRIFE and represent a unique phenotype of SDRIFE, characterized by coexisting extracutaneous manifestations. Onset of systemic stigmata coincided with or preceded cutaneous involvement in 4 and 3 patients, respectively. All patients developed peripheral eosinophilia and 6 patients had ≥ 2 extracutaneous systems involved. Facial involvement, a high-risk feature associated with severe cutaneous adverse reactions but atypical in classic SDRIFE, occurred in 4 cases. Patients had favorable clinical outcomes following drug cessation and treatment with 4-6 week corticosteroid tapers. We suggest that baseline labs be considered in hospitalized patients with antibiotic-induced SDRIFE. These patients may also necessitate systemic therapy given extracutaneous involvement, deviating from standard SDRIFE treatment with drug cessation alone.

TTK inhibitor OSU13 promotes immunotherapy responses by activating tumor STING.

TTK (MPS1) spindle assembly checkpoint kinase is an emerging cancer target. This preclinical study explored the anti-tumor mechanism of TTK inhibitor OSU13 to define a strategy for clinical development. We observed prominent anti-tumor activity of OSU13 in melanoma, colon, and breast cancer cells, melanoma patient-derived organoids, and mice bearing colon tumors associated with G2 cell cycle arrest, senescence, and apoptosis. OSU13-treated cells displayed DNA damage and micronuclei that triggered the cytosolic DNA-sensing cGAS-STING pathway. STING was required for the induction of several proteins involved in T cell recruitment and activity. Tumors from OSU13-treated mice showed an increased proportion of T and NK cells and evidence of PD-1/PD-L1 immune checkpoint activation. Combining a low-toxicity dose of OSU13 with anti-PD1 checkpoint blockade resulted in prominent STING- and CD8 T cell-dependent tumor inhibition and improved survival. These findings provide a rationale for utilizing TTK inhibitors in combination with immunotherapy in STING-proficient tumors.

Giant cell angiofibroma or localized periorbital lymphedema?

Giant cell angiofibroma represents a rare soft tissue neoplasm with a predilection for the orbit. We recently encountered a mass removed from the lower eyelid of a 56-year-old female that histopathologically resembled giant cell angiofibroma. The process consisted of haphazardly arranged CD34-positive spindled and multinucleated cells within an edematous, densely vascular stroma. However, the patient had recently undergone laryngectomy and radiotherapy for a laryngeal squamous cell carcinoma. A similar mass had arisen on the contralateral eyelid, and both had developed several months post-therapy. Lymphedema of the orbit can present as tumor-like nodules and in some cases may share histopathologic features purported to be characteristic of giant cell angiofibroma. A relationship between giant cell angiofibroma and lymphedema has not been established, but our case suggests there may be one. The potential overlap of these two conditions should be recognized, as should other entities that may enter the differential diagnosis.