American Journal of Dermatopathology最新文献

Introduction: The current WHO classification of melanocytic tumors distinguishes 9 pathogenic routes. This classification is based on the conceptual interpretation that melanocytic tumors evolve from benign counterparts, accumulating mutations, eventually developing into melanomas with metastatic and potentially lethal capacity. In this article, we present a molecular study of 2 melanocytic tumors that suggest a "leap" from pathogenic routes IV to I.

Materials and methods: Two recent melanocytic tumors were selected, each exhibiting 2 contiguous melanocytic populations of distinct morphology, without separation between them. One population corresponded to a common melanocytic nevus (with morphology consistent with route I), while the other population displayed epithelioid morphology, consistent with route IV. Immunohistochemical studies were performed in both cases, as well as molecular studies using PCR to search for mutations in the NRAS and BRAF genes. For the molecular study, both populations were manually separated by microdissection.

Results: In both cases, the melanocytic population consistent with route I showed a BRAF mutation. In both cases, the epithelioid population did not present a BRAF mutation. No NRAS mutations were observed in any of the populations.

Conclusions: These findings suggest the existence of a molecular phenomenon of "leap" between pathways, which we have termed "pathway leap." This could explain the enigmatic group of tumors that the WHO classifies under the heading of "combined nevi." This group could be more frequent than suspected, because microdissection is not a technique commonly used in the daily diagnosis of melanocytic tumors.

Abstract: Cutaneous hemophagocytosis is typically known as skin manifestation of syndromal hemophagocytic lymphohistiocytosis, which presents with fever, splenomegaly, cytopenia, hyperferritinemia, and hypertriglyceridemia. Pathophysiologically, an ineffective pathogen elimination has been postulated, which is compensated by excessive macrophage activation. In this study, we present an unusual case of skin limited cutaneous hemophagocytosis within a rare manifestation of a Sweet syndrome triggered by an upper respiratory infection and drug cofactors. A 38-year-old female patient presented with a painful skin rash and a right swollen knee joint that occurred after the onset of streptococcal angina treated with amoxicillin and acetylsalicylic acid. Skin lesions presented as succulent livid red plaques from the forehead to the extensor sides of the upper arms. Clinically, a classical Sweet syndrome was diagnosed by postinfectious onset, distribution and morphology of skin lesions, and abnormal laboratory values including neutrophilic leukocytosis. Histopathologic examination revealed typical characteristics of an acute Sweet syndrome but further showed hemophagocytosis of neutrophils and eosinophils by macrophages. There was a rapid regression of the complaints and skin lesions under systemic high-dose prednisone therapy. Extensive investigations are recommended only if indicators for a syndromal hemophagocytic lymphohistiocytosis are present.

Abstract: Composite hemangioendothelioma comprises permutations of different histological patterns few of which have been found to have specific genetic alteration and immunohistochemical expression. It comprises retiform or epithelioid hemangioendothelioma-like areas, with a variable proportion of hemangioma or low-grade angiosarcoma-like areas. It was found to express neuroendocrine markers and was seen to have a worse prognosis in recurrence or distant metastasis. A 29-year-old woman presented with a lesion of 22 cm in size in her right leg. Biopsy and wide local excision showed features of composite hemangioendothelioma. This is a recurrent lesion after initial resection 2 years back, along with a cutaneous metastasis in the thigh. We report this rare case with a literature review, highlighting the importance of uncommon histomorphology and neuroendocrine marker expression in predicting local recurrence and cutaneous metastasis.

Abstract: Malignant phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm that shows variegated histomorphology and an aggressive clinical course. Cutaneous metastases are rare. A 68 year old woman presented with a palpable left breast mass identified on a routine breast exam. Mammogram showed an oval circumscribed heterogeneous mass measuring 3.7 × 3.7 × 2.7 cm. Patient underwent core needle biopsy with subsequent excision and received a diagnosis of malignant phyllodes tumor with rhabdomyosarcomatous elements with negative margins. The patient suffered a local recurrence 5 months later and was scheduled for re- excision; however prior to that procedure the patient represented to clinic with several cutaneous and subcutaneous nodules located on the left flank, left arm, and bilateral buttocks; described as itchy but not painful. Biopsies of the left flank and the left arm were performed and pathologic examination of both biopsies demonstrated a high- grade rhabdomyoblastic neoplasm that closely resembled so-called pleomorphic rhabdomyosarcoma. The tumor cells in both biopsies marked for immunohistochemical markers of rhabdomyoblastic differentiation and re-review of the original resection specimen showed identical areas confirming the skin and subcutaneous nodules as metastatic malignant phyllodes tumor. We report an unusual case of malignant PT with cutaneous metastases that demonstrated a pure rhabdomyosarcoma phenotype with pleomorphic morphology. Awareness that malignant PT may rarely involve cutaneous sites and present with a pure rhabdomyosarcomatous morphology is important for proper recognition and diagnosis of these tumors, as out of context they may be confused with sarcomas.

Abstract: Primary cutaneous amoebiasis is rare, and typically affects immunocompromised patients and presents with unique clinical and histopathologic changes. Untreated, the infection could progress to involve the central nervous system, which is almost universally fatal. We present a case of primary cutaneous acanthamoebiasis in a patient with chronic lymphocytic leukemia on acalabrutinib. Timely diagnosis and treatment resulted in complete resolution of lesions and a disease-free status at the 14-month follow-up. A 76-year-old man presented with a 2-month history of multiple, nonhealing, ulcerated, erythematous, painful, crusted nodules on his trunk, and upper and lower extremities. Two punch biopsies showed mixed inflammatory infiltrate with a histiocytic reaction and microabscesses extending into the deep dermis. Rare, unusual structures with cytoplasmic vacuolations and round nuclei were seen on repeated biopsies. Gomori methenamine silver delineated wrinkled double-walled cytoplasm of rare parasites, concerning for amoebic infection. Molecular workup (polymerase chain reaction) came back positive for Acanthamoeba castellanii . Initial treatment involved flucytosine and fluconazole, followed by fluconazole and miltefosine, but both were discontinued because of nausea and replaced with single-agent voriconazole. Acanthamoeba cutis poses unique diagnostic challenges in a setting of novel agents for chronic lymphocytic leukemia and may be underrecognized. With the expanding population of immunocompromised patients, rare cutaneous infections should enter the differential early on along with early consideration of molecular ancillary testing. The long-term immunomodulating properties of acalabrutinib remain to be elucidated.

Abstract: In this unusual case, a 73-year-old woman presented with bloody discharge from her right breast and skin thickening was observed on subsequent imaging. Clinically, the findings raised concern for Paget disease. A skin punch biopsy was performed, revealing a high-grade infiltrating carcinoma with squamous features. Metaplastic carcinoma was a differential diagnosis, given that this patient had a history of invasive ductal carcinoma and radiation treatment in the same breast. A subsequent central lumpectomy confirmed the diagnosis of invasive squamous cell carcinoma of the nipple, occurring in the context of Bowen disease as a precursor lesion. Notably, there was no evidence of ductal carcinoma in situ in the background breast tissue or conventional invasive ductal carcinoma component. Both in situ and invasive forms of squamous cell carcinomas have been rarely reported in the nipple. This case highlights the importance of considering such a rare diagnosis, especially in patients with a history of breast cancer.

Abstract: B-Raf Proto-Oncogene (BRAF) fusions are rare in melanomas. We present a case of cutaneous melanoma with a Ring Finger Protein 11 (RNF11)::BRAF fusion in a 63-year-old man with a history of stage IB melanoma on the right upper back (pT2apN0cM0; nonulcerated with a Breslow thickness of 1.2 mm). Despite initial treatment, the melanoma progressed to multiple metastases. Histopathologically, the tumor cells exhibited epithelioid and rhabdoid morphologies, with occasional giant pleomorphic cells and multinucleation, and were positive for antimelanocytic cocktail (HMB45, Melan-A, tyrosinase) and S100. Next-generation sequencing of a metastatic specimen identified an RNF11::BRAF fusion and TERT promoter mutation, but no other somatic mutations (eg, BRAF, NRAS, KIT) or copy number variations were detected. The patient died to melanoma approximately 58 months after initial diagnosis, despite several lines of systemic therapy, including immunotherapies and a mitogen-activated protein kinases 1 and 2 inhibitor. RNF11::BRAF fusions are known oncogenic drivers in histiocytic disorders such as Erdheim-Chester disease and non-Langerhans cell histiocytosis. Although BRAF fusions are commonly observed in Spitz melanocytic neoplasms, the discovery of the RNF11::BRAF fusion in melanomas is unprecedented. Our case represents a triple wild-type, clinically aggressive melanoma of possibly non-Spitz lineage with an ultraviolet signature and a rare BRAF fusion, contributing to the expanding body of literature on BRAF-fused melanomas.