American Journal of Dermatopathology最新文献

Aims: Limited studies have been conducted on juvenile conjunctival nevus (JCN) in Asian populations. This study aims to investigate the clinical and pathologic characteristics of JCN cases among the Han ethnicity in northwest China, providing insights for pathologists and ophthalmologists in diagnosing this condition.

Methods: A subset of conjunctival nevi in children and adolescents, characterized by a confluent growth pattern and lack of maturation, was identified and defined as JCN. A retrospective analysis of the clinicopathologic features of these cases was performed.

Results: The study included 40 patients aged 3-20 years, with a median age of 15.5 years. Six cases involved congenital conjunctival pigmentation. Twenty-four were male patients and 16 were female patients, with a male-to-female ratio of 1.5:1. Microscopically, nevus cells grew confluently within or beneath the epidermis and exhibited moderate cellular atypia. In some cases, the junction of the epithelium and the lamina propria layer was obscured by the integration of nevus cell clusters, mimicking epithelial invasion and potentially leading to a misdiagnosis. Over an average follow-up of 78.5 months, no recurrence or postoperative complications were observed.

Conclusions: Diagnosing JCN is challenging because of its histologic resemblance to conjunctival melanoma. A systematic analysis of JCN can improve the recognition of its benign nature by pathologists and ophthalmologists, helping to prevent overdiagnosis of conjunctival malignant melanoma in this young population.

Abstract: Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. It is characterized by the presence of neoplastic lymphoid cells within blood vessels. We report a rare case of IVLBCL with exclusively cutaneous involvement colonization of hemangiomas. A 55-year-old man with a history of cutaneous angioma consulted dermatology because of the growth of some of the hemangiomas in recent months. Histologic examination revealed a dermal proliferation of small- and medium-sized vessels with lumina occupied by large pleomorphic cells with B immunophenotype and aberrant expression of HMB-45. Biopsy of a pre-existing hemangioma may be useful in the diagnosis of suspected cutaneous IVLBCL. The cutaneous variant has a better prognosis. It is also important to note that unexpected protein expression or loss of expression in malignant tumors may be a risk factor for misdiagnosis.

Abstract: Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis that is difficult to diagnose due to non-specific clinical, laboratory, and histopathologic features. Distinguishing pseudoepitheliomatous hyperplasia (PEH) from squamous cell carcinoma (SCC) is also histopathologically challenging. The connection between PEH and PG is not well recognized, and instances of PG mimicking SCC are rare. We report a case of vegetative PG accompanied by PEH, originally mistaken for SCC. A 78-year-old woman presented with a 3-month history of an ulcerated, exophytic, and painful mass on her right lower leg. An incisional biopsy revealed PEH and neutrophilic microabscesses, initially raising concerns for SCC keratoacanthoma type with PEH or well-differentiated, infiltrative SCC. However, following additional review of clinical and histopathologic findings at the cutaneous oncology tumor board, the diagnosis of vegetative PG with associated PEH was favored. This case highlights the significance of recognizing PEH as a histopathology feature that can be seen in PG and lead to difficulty distinguishing PG with PEH from SCC. We stress the importance of promptly diagnosing PG through clinical and histopathologic correlation to prevent diagnostic delays and unnecessary surgeries or treatments.

Abstract: The tumor microenvironment plays a critical role in malignant melanoma, influencing progression and patient outcomes, particularly through tumor budding (TB) and tumor-infiltrating lymphocytes (TILs). Despite the importance of TB, its detailed impact still needs to be explored, especially its interaction with TILs. This study evaluates the prognostic significance of TB and TILs in malignant melanoma, assessing their potential as indicators for disease progression and survival. Conducted at Akdeniz University, the research included 92 patients diagnosed between 2014 and 2021. TB was evaluated according to the International Tumor Budding Consensus Conference guidelines, and TILs were assessed by the International Immuno-Oncology Biomarker Working Group standards. The analysis revealed significant correlations between TB and the level of anatomic invasion, Breslow thickness, satellite nodules, lymph node metastasis, distant metastasis, and stage ( P < 0.05). A notable inverse relationship between TB and intratumoral TILs suggested their different roles in tumor progression. Tumor subtype, level of anatomic invasion, satellite nodules, lymphovascular invasion, lymph node metastasis, distant metastasis, stage, TILs, and TB were significant risk factors associated with poor prognosis ( P < 0.005). Multivariate Cox regression identified histologic subtype and TB >10 as independent prognostic factors, underscoring the need for further research to integrate TB and TILs into clinical practice for better patient management and treatment planning.

Abstract: Superficial CD34 + fibroblastic tumor (SCD34FT) is a relatively recently described borderline mesenchymal neoplasm. Owing to a relative lack of specificity in clinical presentation, radiopathologic findings, and immunohistochemical staining, the diagnoses of SCD34FT can be challenging. In this study, we present a case of a 55-year-old woman with an indolent painless nodule on the right shin. Histopathologic evaluation of the resected specimen showed a moderately cellular, subcutaneous lesion composed of spindled cells with mild pleomorphism arranged in sheets and fascicles. Immunohistochemical staining demonstrated diffuse positivity for CD34. Surprisingly, the tumor also showed diffuse expression of smooth muscle actin (SMA) and more than focal (ranging from subset to diffuse) expression of AE1/AE3 and CAM5.2. DNA and RNA next-generation sequencing revealed a t(X; 11)(q13; q24) MED12::PRDM10 fusion, confirming the diagnosis of SCD34FT. To the best of our knowledge, this is the first reported case highlighting SCD34FT with more extensive immunoreactivity to epithelial markers (AE1/AE3 and CAM5.2) and SMA compared with the focal staining reported in the existing literature. We hope that adding this case to the existing literature will raise awareness among pathologists to recognize the more variable staining pattern of epithelial markers and SMA when considering the diagnosis of SCD34FT.

Abstract: Breast cancer1-associated protein 1 (BAP-1)-inactivated melanocytic tumors are a group of familial or sporadic lesions with distinctive histology and molecular features. Inherited germline inactivating mutations in BAP1 have been associated with the development of multiple epithelioid melanocytic neoplasms resembling Spitz nevi and increased susceptibility for developing several malignancies, including uveal melanoma, cutaneous melanoma, renal cell carcinoma, mesothelioma, and other tumors. Cutaneous melanoma with loss of BAP1 expression is rare. We present a unique case of BAP1 -inactivated melanoma with anaplastic lymphoma kinase ( ALK ) fusion arising in a pre-existing BAP1 -inactivated nevus in a 47-year-old female patient who presented with a dome-shaped red papule on the superior crus of the right antihelix. Histology revealed intradermal melanocytic proliferation with biphenotypic morphology. There was a proliferation of atypical melanocytes showing epithelioid features in the background of nevus. Mitotic figures were identified in the cytologically atypical component of the lesion. Mart-1/Ki67 dual stain demonstrated a higher proliferation index in the larger epithelioid atypical cells, supporting the diagnosis of melanoma. Nuclear BAP-1 expression was lost in the larger atypical cells and associated nevoid cells. Preferentially expressed antigen in melanoma stain demonstrated focal positive staining in 20%-30% of the melanocytes. Immunostaining for B-Raf proto-oncogene, serine/threonine kinase V600E was diffusely positive and ALK demonstrated patchy immunoreactivity in the melanocytic proliferation. Interphase fluorescence in situ hybridization studies showed gains at chromosome 6p25 (Ras responsive element binding protein 1) in the tumor cells. The comprehensive next-generation sequencing revealed B-Raf proto-oncogene, serine/threonine kinase V600E mutation, TP53 mutation, ALK fusion, BAP1 loss (copy number variation = 0.0, potentially germline), and loss of MAP2K7, Von Hippel-Lindau tumor suppressor, FGFR3, CDKN2A , 19q, and telomerase reverse transcriptase . The tumor was microsatellite stable with a low tumor mutational burden (5.76 mutations/Mb). The tumor was completely excised with negative margins. The patient is doing well at 17 months follow-up with no signs of recurrence.

Background: Thiotepa, an alkylating agent commonly used in chemotherapy, is increasingly recognized to induce cutaneous reactions resembling toxic erythema of chemotherapy (TEC). This condition is characterized by erythema, hyperpigmentation, and mucositis, often affecting intertriginous areas, and can mimic the early stages of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

Case description: A 31-year-old woman with a history of systemic lupus erythematosus, antiphospholipid antibody syndrome, seizures, and chronic kidney disease was admitted for the management of central nervous system (CNS) lymphoma. Seven days after receiving thiotepa during an autologous stem cell transplant, she developed severe mucositis, requiring intubation for airway protection, followed by a dusky, gray, full-body rash with sloughing in the groin, axillae, and buttocks. A skin biopsy from the back revealed vacuolar interface changes, eccrine gland necrosis, and occasional necrotic keratinocytes at the dermal-epidermal junction, with no evidence of full-thickness necrosis or significant eosinophilic infiltration. The differential diagnosis included thiotepa-induced toxicity, SJS/TEN, and drug eruption. Based on the patient's clinical presentation and the biopsy findings, thiotepa-induced TEC was favored over SJS/TEN.

Discussion: Thiotepa is a potent lipophilic alkylating agent widely used in chemotherapy for pediatric and adult patients with various solid tumors and hematologic malignancies. Its anticancer mechanism involves DNA alkylation, leading to DNA strand cross-linking that disrupts replication and transcription, ultimately inhibiting cancer cell proliferation and survival. While thiotepa is primarily utilized in high-dose preparative regimens for stem cell transplantation in pediatric patients, its use in the adult population remains comparatively limited.This case emphasizes the importance of differentiating thiotepa-induced TEC from severe cutaneous adverse reactions such as SJS/TEN. While these conditions share clinical and histologic features, the absence of extensive epidermal necrosis, satellite cell necrosis, and systemic involvement, along with recent thiotepa exposure, supported a diagnosis of TEC.

Conclusions: This case highlights the diagnostic challenge of distinguishing thiotepa-induced TEC from SJS/TEN in post-transplant patients. Recognizing the characteristic involvement of intertriginous areas and eccrine gland necrosis in TEC is critical for accurate diagnosis and management. Awareness of this potential complication in patients receiving thiotepa is essential to avoid misdiagnosis and inappropriate treatment.