American Journal of Dermatopathology最新文献

Abstract: Hepatocellular carcinoma (HCC) rarely metastasizes to the skin. When it occurs, it is often poorly differentiated making the diagnosis challenging. There exists a male predominance, and clinical presentation usually includes papules or nodules resembling pyogenic granulomas or dermal deposits. Histopathology shows malignant dermal cells. Hepatoid features including nests or cords of cells arranged in a trabecular or pseudoglandular pattern, sinusoidal formation, or the presence of bile exist in less than 50% of cases. Limitations exist with immunohistochemical staining, particularly in poorly differentiated neoplasms. Albumin in situ hybridization is more sensitive for detecting poorly differentiated HCC. Immunostaining in conjugation with albumin in situ hybridization enhances the detection of metastatic hepatocellular carcinoma. We report the case of a 74-year-old man with a history of HCC and a stable lung metastasis who presented with painful, growing bumps on his nose for 2 months. Examination revealed multiple, pink to white, shiny dermal-based papules with telangiectasias involving the right nasal tip and naris. Alpha-fetoprotein level was markedly elevated. Computed tomography showed expanding right lower lobe lung nodules. Histopathology of the cutaneous biopsy revealed features of a poorly differentiated basaloid carcinoma. Immunohistochemical staining was diffusely positive for glypican-3, focally positive for arginase-1, and negative for hepatocyte paraffin 1. Albumin in situ hybridization was diffusely positive, clinching the diagnosis of HCC. Metastatic HCC is a rare encounter for dermatopathologists. We aim to increase awareness of its occurrence in patients with advanced HCC and highlight the importance of clinical correlation when faced with poorly differentiated or unusual-looking basaloid neoplasms.

Abstract: Microtubule-stabilizing agents (enfortumab vedotin and brentuximab vedotin) and microtubule-disrupting agents (docetaxel and paclitaxel) are used as anticancer agents but can also induce drug eruptions. Recently, mitotic arrest figures have been reported in various non-neoplastic cells as the histopathologic side effect of these drug eruptions. Therefore, we performed a comparative analysis of drug eruptions associated with these microtubule-targeting agents. Enfortumab vedotin-, brentuximab vedotin-, docetaxel-, and paclitaxel-associated drug eruptions were retrieved from 4 hospitals in 5, 5, 5, and 7 patients, respectively. Ring mitotic and other mitotic arrest figures were observed in the epidermis in all types of drug eruption but were most frequently (100%) observed in enfortumab vedotin-induced eruptions. Such a finding was also occasionally observed in the sweat ductoglandular units but not in the follicular epithelium. Keratinocyte multinucleation and apoptotic keratinocytes distributed predominantly in the upper part of the epidermis were also observed in these eruptions, particularly in enfortumab vedotin-induced eruptions (4/5, 80%). In conclusion, drug eruptions associated with microtubule-targeting agents, particularly enfortumab vedotin, can often exhibit mitotic arrest figures, keratinocyte multinucleation, and apoptotic keratinocytes predominantly observed in the upper part of the epidermis. These characteristic histopathologic features can be the diagnostic clues of drug eruptions induced by microtubule-targeting agents.

Abstract: Primary effusion lymphoma (PEL) is a rare and aggressive B-cell lymphoma typically associated with human herpesvirus 8 (HHV-8) and Epstein-Barr virus infections. It classically presents as a malignant effusion in body cavities, but rarely presents with an extracavitary variant characterized by solid tumors in lymph nodes or extranodal sites such as the gastrointestinal tract, skin, lungs, and nervous system. This case report describes an unusual presentation of primary cutaneous extracavitary PEL in an HIV-positive patient that has only been reported in 8 cases previously. The patient presented with a skin nodule in the right supraclavicular area. Histopathologic examination showed a malignant infiltrate in the dermis composed of sheets of plasmablasts. The immunophenotype of the cells shows the characteristic coinfection with HHV-8 and Epstein-Barr virus. The case presented herein contributes to expand the reported literature on primary cutaneous extracavitary PEL and performs a comprehensive review of this entity, which most dermatopathologists are unfamiliar with.

Introduction: Leishmaniasis, a chronic vector-borne disease caused by parasites of the genus Leishmania , presents diagnostic challenges. Conventional diagnostic methods struggle with accurate visualization of these parasites. Immunostaining with CD1a has demonstrated effectiveness in visualizing Leishmania parasites, particularly in the Old World. However, the application of CD1a immunostaining in Colombian leishmaniasis remains unexplored.

Objective: To determine the utility of CD1a as an immunomarker in detecting chronic forms of tegumentary leishmaniasis.

Materials and methods: This proof-of-concept study involved 48 paraffin-embedded samples categorized into 3 groups: moderate-to-high parasite load (n = 15), low load (n = 15), and chronic granulomatous inflammation (n = 13); 5 samples diagnosed with cutaneous histoplasmosis. These samples were stained with the immunomarker CD1a clone EP3622 for comparative analysis. In addition, CD1a immunohistochemistry was compared with 18S rDNA qPCR and hematoxylin-eosin staining to evaluate its performance in relation to these established methods.

Results: CD1a immunohistochemistry was positive in 46.51% of the samples evaluated. This immunomarker showed lower sensitivity and negative predictive value than 18S rDNA qPCR and hematoxylin-eosin staining; specificity and negative predictive value were consistent. ROC indicated inferior discrimination for leishmaniasis compared with 18 s rDNA qPCR and hematoxylin-eosin staining.

Conclusions: Immunohistochemistry for CD1a could be a diagnostic support in the detection of chronic forms of tegumentary leishmaniasis.

Abstract: Skin biopsy plays a fundamental role in the diagnosis of vasculitis. However, the general pathologist or dermatopathologist who encounters these diagnostic findings in their early stages often faces the paradox that the clinician requests the exclusion of various systemic diseases, when the biopsy only shows leukocytoclastic vasculitis. In other cases, even though the affected vessels are small, some of them seem deep within the biopsy, raising differential diagnosis with several entities of systemic repercussion. Lastly, although the dermatopathologist has a histological picture before them, they are often required to correlate it with laboratory data such as the presence of antineutrophil antibodies, for example. Therefore, the objective of this article is conceptual, emphasizing those basic aspects that can contribute to a better understanding and diagnosis of skin biopsy in vasculitis.

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.