International Journal of Surgical Pathology最新文献

Colorectal large-cell neuroendocrine carcinoma, a rare and aggressive type of cancer, accounts for <0.6% of all colorectal cancers. Neuroendocrine carcinomas are associated with hereditary conditions such as Lynch syndrome; however, their co-occurrence with familial adenomatous polyposis (FAP) is poorly documented. To date, only 1 patient of colorectal neuroendocrine carcinoma in a patient with FAP has been reported. This report presents a patient with FAP. Large-cell neuroendocrine carcinoma with lymph node metastasis was discovered during right colectomy. Histopathological and immunohistochemical assessments confirmed neuroendocrine differentiation with a high Ki-67 index (>90%). Genetic analysis revealed a pathogenic germline APC mutation and somatic alterations in APC, TP53, RB1, PALB2, MAP3K1, NTRK3, and KRAS. Adjuvant chemotherapy commenced postoperatively. No evidence of recurrence was observed for 18 months postoperatively. This case report highlights the rare presentation of colorectal large-cell neuroendocrine carcinoma in a patient with FAP, thereby contributing to the limited literature on this association. APC mutations have been characterized in adenomatous polyposis and colorectal adenocarcinomas; however, their role in the pathogenesis of neuroendocrine carcinoma remains unclear. Additional mutations of TP53, RB1, PALB2, MAP3K1, NTRK3, and KRAS suggest a unique molecular profile that may contribute to the development of neuroendocrine carcinoma in patients with FAP. This is the second reported patient of colorectal large-cell neuroendocrine carcinoma in a patient with FAP. Further studies must be conducted to elucidate the role of APC mutations in the pathogenesis of neuroendocrine tumorigenesis.

The malignant transformation of schwannomas is exceptionally rare and typically results in a malignant peripheral nerve sheath tumor (MPNST). We report a unique patient with malignant transformation of a schwannoma into an S-100 negative epithelioid MPNST. A 72-year-old male patient presented with an abdominal mass, and imaging revealed a 5 cm tumor in the rectus abdominis muscle, which was diagnosed as schwannoma through biopsy. The patient opted for observation instead of surgery. Eight years later, the tumor had enlarged to 10 cm, accompanied by worsening pain. Imaging showed intra-abdominal dissemination and metastases to mediastinal and para-aortic lymph nodes. Comprehensive whole-body positron emission tomography and computed tomography imaging and meticulous re-examination of the original schwannoma biopsy definitively excluded alternative primary malignancies and established histopathological continuity between the current lesion and the pre-existing schwannoma. Immunohistochemical staining indicated the tumor was S-100 negative, SOX10 negative, H3K27me3 positive, SMARCB1/INI1 positive and EMA negative, leading to the diagnosis of S-100 negative epithelioid MPNST. Due to the rapid tumor growth, palliative radiation therapy was administered, and the patient received best supportive care. This patient was identified as an S-100 negative epithelioid MPNST.

Background: This study investigates the interplay between PD-L1, FOXP3+ regulatory T cells, and CD8+ cytotoxic T lymphocytes in penile squamous cell carcinoma (penile SCC), where understanding the tumor immune microenvironment is crucial. Methods: We analyzed 108 penile SCC specimens using tissue microarrays (528 spots). Immunohistochemistry was performed for PD-L1, FOXP3, and CD8. Expression was quantified in tumor and stromal compartments, and correlated with clinicopathological features including histological grade, HPV-associated morphology, and host inflammatory response. Results: PD-L1 in tumor cells positively correlated with intratumoral CD8+ (rho = 0.408, P < .001) and FOXP3+ T cells (rho = 0.293, P = .009). Peritumoral FOXP3+ and CD8+ T cells also showed a strong correlation (rho = 0.753, P < .001). Higher PD-L1 and intratumoral CD8+ were associated with higher histological grade (P < .001). HPV-associated morphology correlated with higher PD-L1 (P < .001) but lower FOXP3+ infiltration (P < .001). Intense inflammatory response was associated with increased peritumoral FOXP3+ and CD8+ T cells (P < .001). Conclusions: The immune microenvironment of penile SCC involves complex interactions among PD-L1, FOXP3+, and CD8+, and was significantly influenced by histological grade, HPV status, and inflammation. The strong co-localization of peritumoral regulatory and cytotoxic T cells suggests a critical regulatory axis. These findings highlight distinct immune profiles within penile SCC, offering insights for developing tailored immunotherapeutic strategies.

"Collision tumors" are a phenomenon that occur when two neoplasms concomitantly localize next to each other. Malignant melanoma of the bladder is an uncommon entity with less than 40 reported instances and is exceedingly rare to present as a collision tumor. In this report, we present a collision tumor consisting of a primary bladder malignant melanoma and invasive high-grade papillary urothelial carcinoma. The clinical presentation and cytomorphologic, immunophenotypic, and molecular findings of this tumor are depicted. Additionally, we also briefly discuss an overview of cutaneous versus mucosal melanomas, focusing on those reported in the genitourinary tract. To the best of our knowledge, this is the second report in literature of a collision between malignant bladder melanoma and urothelial carcinoma occurring in the bladder and the first to involve an invasive urothelial carcinoma.

Alveolar soft part sarcoma (ASPS) is a rare and distinctive subtype of soft tissue sarcoma accounting for <1% of all sarcomas. Characterized by the t(X;17)(p11;q25) translocation, it typically affects the extremities in younger individuals. This case report presents a bladder ASPS in a 45-year-old woman, a rare occurrence, developing as a second primary malignancy following breast cancer treatment. Histopathological analysis, immunohistochemistry and molecular diagnostics confirmed the diagnosis. The patient underwent partial cystectomy with clear surgical margins and remained recurrence-free 38 months post-resection. This report highlights the diagnostic challenges, therapeutic strategies, and the importance of long-term surveillance for bladder ASPS.

BackgroundThe balance between CD8+ cytotoxic T cells and FOXP3+ regulatory T cells within the tumor microenvironment is crucial in cancer progression. This study aimed to characterize CD8+/FOXP3+ T-cell ratios in tumor and stromal compartments of penile squamous cell carcinoma (SCC) across different histologic subtypes and grades.MethodsThis retrospective study analyzed 1 tissue microarray block (144 spots from 35 patients). CD8 and FOXP3 immunohistochemistry was performed. Ratios of CD8+/FOXP3+ T cells per high-power field were categorized as CD8 > FOXP3 or CD8 ≤ FOXP3 in tumor and stromal compartments. Associations with histologic subtype (including WHO classification) and grade were examined.ResultsSeventy-nine spots (55%), representing 23 unique patients, were evaluable. Median intratumoral CD8+ and FOXP3+ counts were 5 and 4 per high-power field, respectively. Stromal median counts were 22 (CD8+) and 38 (FOXP3+) per high-power field. No statistically significant associations were found between CD8+/FOXP3+ ratios and histologic grade in either tumor (P = .529) or stromal compartments (P = .660). Similarly, no significant associations were observed with histologic subtype, though a non-significant trend (P = .09) was noted between stromal ratio and subtype.ConclusionsThis study characterized CD8+ and FOXP3+ T-cell infiltrates and their ratios in penile SCC, revealing distinct patterns between tumor and stromal compartments. In this cohort, significant associations with histologic grade or subtype were not observed. These findings underscore the need for larger, prospective studies incorporating HPV status and clinical outcomes to elucidate the role of these immune ratios.

Myeloid sarcoma is an extramedullary mass lesion composed of myeloid blasts that disrupt tissue architecture. Myeloid sarcoma in the prostate is exceptionally rare, with fewer than 30 patients reported. Among these, 8 have been observed without a prior diagnosis of a hematolymphoid neoplasm. To date, concurrent prostatic myeloid sarcoma and adenocarcinoma have not been documented in the English-language literature. We present the first 2 myeloid sarcomas in the prostate occurring concurrently with high-grade prostatic adenocarcinoma, identified on core needle biopsy and radical prostatectomy in patients without a prior history of myeloid sarcoma or acute myeloid leukemia (AML), and highlight the associated diagnostic challenges. Both were positive for NPM1 by immunohistochemistry, consistent with NPM1 mutation. Neither patient received treatment for myeloid sarcoma/AML due to multiple comorbidities. One patient succumbed to the disease 44 days after diagnosis, while the other passed away from respiratory failure in the context of multiple comorbidities 2 months after being diagnosed with myeloid sarcoma.

Neuroblastomas in adults are extremely rare and are generally regarded to have poorer outcomes compared to infants and children. Due to the scarcity of data among adult patients with neuroblastoma, treatment guidelines are also not well established. These tumors are derived from primitive neural crest cells and fall under a broader category of small round blue cell tumors which can pose diagnostic challenges in atypical scenarios like adult patients or atypical primary sites. Accurate diagnosis is vital to appropriate patient management. We present one such rare occurrence of a mediastinal neuroblastoma in a 31-year-old adult woman presenting with neurological symptoms after a prolonged indolent course.

Endometrial stromal tumors comprise a spectrum of lesions ranging from benign nodules to malignant sarcomas. Endometrial stromal sarcomas are classified as either low-grade or high-grade based on morphologic, immunophenotypic, and genetic features. The majority of low-grade endometrial stromal sarcomas of the uterus are characterized by recurrent chromosomal translocations producing specific gene fusions, with JAZF1::SUZ12 being the most common. While endometrial stromal sarcomas typically originate in the uterine corpus, the neoplasm can rarely manifest as an extrauterine tumor in the absence of uterine involvement (endometrioid stromal sarcoma or extrauterine endometrial stromal sarcoma). Herein, we present a case report of a 55-year-old woman presenting with an intra-abdominal mass incidentally found on renal ultrasound performed for chronic kidney disease. Resection revealed irregular nodules of tumor permeating mesenteric soft tissue, composed of small, uniform ovoid to spindled cells expressing CD10, estrogen receptor, and WT1. Gross and microscopic evaluation of the accompanying hysterectomy specimen showed no uterine involvement by the tumor. Fluorescent in-situ hybridization (FISH) study performed on the mesenteric mass demonstrated the presence of a JAZF1 gene rearrangement. The patient was diagnosed with low-grade endometrioid stromal sarcoma and placed on adjuvant hormone therapy without clinical or imaging recurrence at 18-month follow-up. This case report underscores the utility of FISH as a potential confirmatory diagnostic tool in specimens of suspected extrauterine endometrial stromal sarcoma.

BackgroundMyxofibrosarcoma (MFS) and undifferentiated soft tissue sarcoma (USTS) are common sarcoma subtypes with overlapping molecular features. Both are treated with neoadjuvant radiotherapy followed by surgery, yet radiotherapy response is variable and unpredictable. This study investigated DNA methylation and copy number variation (CNV) profiles obtained from pre-radiotherapy biopsies as predictive biomarkers of radiotherapy response.Patients and methodsPre-radiotherapy biopsies and post-radiotherapy resections were obtained from 49 patients (27 MFS, 22 USTS). Radiotherapy response was assessed on the resection specimens using the EORTC-STBSG 5-tier system; grades A-C (<10% viable tumor) were classified as responders, D-E (≥10% viable tumor) as non-responders. Genome-wide DNA methylation and CNV data were generated from the pre-radiotherapy biopsies using Illumina MethylationEPIC BeadChips and were correlated with response grades.ResultsDNA methylation profiling yielded evaluable results in 23/49 tumors (15 MFS, 8 USTS), with 9 responders and 14 non-responders. Unsupervised methylation clustering, incorporating public datasets, showed that MFS, USTS, and pleomorphic liposarcomas formed a single, heterogeneous cluster. Similarly, CNV profiles did not distinguish MFS from USTS. Methylation patterns did not significantly differ between responders and non-responders. CNV profiles were largely comparable between responders and non-responders, except of a significantly higher frequency of chromosome 11q24.1 loss in responders compared to non-responders (100% vs 33%; P = 0.0039).ConclusionsOur findings support the concept that MFS and USTS represent a spectrum of the same disease. We could not demonstrate the value of DNA methylation profiling in radiotherapy response prediction. However, 11q24.1 loss may represent a potential predictive biomarker and merits further validation.