The exact relationship between solid papillary carcinoma (SPC) and invasive breast carcinoma of no special type (IBC-NST) with neuroendocrine differentiation and SPC and mucinous carcinoma (MC) of the breast remains unclear. To clarify the relationship, we conducted a comparative study of morphological and neuroendocrine features between ductal carcinoma in situ (DCIS, 72 cases) and SPC in situ (35 cases), and IBC-NST (103 cases) and invasive SPC (92 cases). We also conducted the study between MC associated with and without SPC. Synaptophysin, chromogranin A, and INSM1 were employed for the immunohistochemical study. IBC-NST had occasionally a morphological similarity with invasive SPC. While 123 of 127 cases with SPC demonstrated diffuse staining with one or more of the neuroendocrine markers, the only one case of DCIS and none of IBC-NST showed it. Type B was observed in 16 of 18 cases of MC associated with SPC and in 13 of 33 cases of MC without it. All the cases of MC with SPC and 6 of 33 cases without it showed diffuse staining for at least one of the neuroendocrine markers. In conclusion, a careful distinction between invasive SPC and IBC-NST with neuroendocrine differentiation is required. We assume that SPC in situ is a potential candidate for precursor of IBC-NST with neuroendocrine differentiation. MC of the breast is suggested to have two pathogenetic pathways through SPC in situ or non-SPC in situ. SPC in situ is thought to be less common as a precursor of MC than non-SPC in situ.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous tumour with high mortality and frequently delayed diagnosis. Clinically, it often manifests as a rapidly growing erythematous to purple nodule usually located on the lower extremities or face and scalp of elderly patients. There is limited available data on the dermoscopic findings of MCC, and there are no specific features that can be used to definitively diagnose MCC.
OBJECTIVE: Here, we aimed to summarize existing published literature on dermatoscopic and reflectance confocal microscopy (RCM) features of MCC.
METHODS: To find relevant studies, we searched the PubMed and Scopus databases from inception to April 12, 2023. Our goal was to identify all pertinent research that had been written in English. The following search strategy was employed: (\" dermoscopy\" OR \" dermatoscopy\" OR \" videodermoscopy\" OR \" videodermatoscopy\" OR \" reflectance confocal microscopy\") AND \" Merkel cell carcinoma\". Two dermatologists, DK and GE, evaluated the titles and abstracts separately for eligibility. For inclusion, only works written in English were taken into account.
RESULTS: In total 16 articles were retrieved (68 cases). The main dermoscopic findings of MCC are a polymorphous vascular pattern including linear irregular, arborizing, glomerular, and dotted vessels on a milky red background, with shiny or non-shiny white areas. Pigmentation was lacking in all cases. The RCM images showed a thin and disarranged epidermis, and small hypo-reflective cells that resembled lymphocytes arranged in solid aggregates outlined by fibrous tissue in the dermis. Additionally, there were larger polymorphic hyper-reflective cells that likely represented highly proliferative cells.
CONCLUSIONS: Dermoscopic findings of MCC may play a valuable role in evaluating MCC, aiding in the early detection and differentiation from other skin lesions. Further prospective case-control studies are needed to validate these results.

UNASSIGNED: Large cell neuroendocrine carcinomas of the colon (LCNECC) are exceptionally rare, comprising only 0.2 % of all colonic carcinomas. Their diagnosis poses a significant challenge due to their propensity to mimic colonic adenocarcinomas. Typically diagnosed at advanced stages, LCNECCs carry a grim prognosis. Herein, we present a rare case of LCNECC and aim to elucidate its clinico-pathological characteristics.
METHODS: A 56-year-old female patient presented with complaints of constipation, abdominal pain, and weight loss. On physical examination, a sizable mass was palpable in the right flank. Colonoscopy revealed a polyp in the descending colon and a friable multinodular stenosing mass in the ascending colon. Microscopic examination of the biopsy from the ascending colon mass exhibited a poorly differentiated large cell carcinomatous proliferation with positivity for synaptophysin and CD56, along with a Ki-67 proliferation index of 50 %. The polyp in the descending colon was consistent with a low-grade dysplastic tubular adenoma. A diagnosis of LCNECC with synchronous low-grade dysplastic tubular adenoma was established. A right hemicoloctomy was performed. Final pathological examination confirmed LCNECC invading the muscularis propria, with lymph node metastases. The tumor was classified as pT2N1M0 (Stage III).
UNASSIGNED: LCNECCs often mimic adenocarcinomas clinically, endoscopically, and radiologically. Pathological examination is the key for diagnosis. An immunohistochemical study using neuroendocrine markers is imperative to prevent overlooking the diagnosis of LCNECC.
CONCLUSIONS: LCNECCs represent rare aggressive carcinomas. Their diagnosis might be challenging. A better knowledge of this rare entities would enable early diagnosis.

BACKGROUND: Prostate cancer presents with soft tissue progression (STP) is highly aggressive. We analyzed the risk factor for STP in patients with metastatic castration-resistant prostate cancer (mCRPC) who developed abiraterone acetate (AA) resistance.
METHODS: This retrospective study included patients with mCRPC who received AA between February 2018 and July 2022. STP was defined as recurrent lesions in situ, multiple regional lymph node metastases (mLNM), or visceral metastases. Clinical features of patients with STP were analyzed, and risk factors for STP were further investigated.
RESULTS: Sixty-three patients (mean age, 75.0 years; median follow-up time, 22.3 months) were included in this study. Twenty-three patients (36.5%) presented STP during follow up, the overall survival (OS) after STP was 4.6 months. The serum neuron-specific enolase (NSE) were significantly elevated in patients with STP. Biopsies for 8 patients with STP showed neuroendocrine prostate cancer (NEPC, n = 5) was the major pathological types. Further analysis showed that perineural invasion (PNI) in primary tumor were the independent risk factors (HR = 3.145, P = 0.020) for STP, and PNI was related to the aggressiveness of tumor. Patients with PNI showed shorter castration-resistant progression free survival (median, 23.73 months vs. 25.59 months) and STP progression free survival (median, 19.7 months vs. not reached) compared with patients without PNI.
CONCLUSIONS: STP showed extremely poor prognoses in patients with mCRPC after AA resistance, NEPC is the main pathological type of STP, and PNI in primary tumor was an independent risk factor for STP and indicated poor prognosis of prostate cancer.

Background: Neuroendocrine carcinomas (NECs) of the tubular gastrointestinal tract (GI-NECs) are rare and associated with worse clinical outcomes. This population-based study aims to highlight key demographics, clinicopathological factors, and survival outcomes in the US population. Methods: Data from 10,387 patients with GI-NECs were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2000 to 2020. Results: Most patients were >40 years old at the time of presentation with a median age of 63 years old, with almost equal ethnic distribution per US population data. The most common primary tumor site was the small intestine (33.6%). The metastatic spread was localized in 34.8%, regional in 27.8%, and distant in 37.3% of cases, and the liver was the most common site of metastasis (19.9%) in known cases of metastases. Most NEC patients underwent surgery, presenting the highest 5-year overall survival of 73.2% with a 95% confidence interval (CI) (95% CI 72.0-74.4%), while chemotherapy alone had the lowest 5-year survival of 8.0% (95% CI 6.4-10.0%). Compared to men, women had a superior 5-year survival rate of 59.0% (95% CI 57.6-60.5%). On multivariate analysis, age > 65 (HR 2.49, 95% CI 2.36-2.54%, p ≤ 0.001), distant metastasis (HR 2.57, 95% CI 2.52-2.62%, p ≤ 0.001), tumor size > 4 mm (HR 1.98, 95%, CI 1.70-2.31%, p ≤ 0.001), esophageal (HR 1.49, 95% CI 0.86-2.58%, p ≤ 0.001), transverse colon (HR 1.95, 95% CI 1.15-3.33%, p ≤ 0.01), descending colon (HR 2.12, 95% CI 1.12, 3.97%, p = 0.02) anorectal sites, and liver or lung metastases were associated with worse survival. Surgical intervention and tumors located in the small intestine or appendix showed a better prognosis. Conclusion: GI-NECs are a group of rare malignancies associated with a poor prognosis. Therefore, epidemiological studies analyzing national databases may be the best alternative to have a more comprehensive understanding of this condition, assess the impact of current practices, and generate prognosis tools.

UNASSIGNED: Renal neuroendocrine neoplasms (R-NEN) are exceptionally rare tumours characterized by high mortality rates.
UNASSIGNED: The objective of this study is to analyse prognostic factors and treatment impact on overall survival in patients with R-NEN.
UNASSIGNED: We identified all patients with R-NEN in the National Cancer Database (NCDB) from 2004 to 2019 and identified prognostic factors for improved survival.
UNASSIGNED: Of 542 R-NEN cases, 166 (31%) were neuroendocrine tumour grade 1 (NET-G1), 14 (3%) were neuroendocrine tumour grade 2 (NET-G2), 169 (31%) were neuroendocrine carcinoma (NEC-NOS), 18 (3%) were large cell neuroendocrine carcinoma (LC-NEC) and 175 (32%) were small cell neuroendocrine carcinoma (SC-NEC). Median overall survival for all patients in the study was 44.88 months (SE, 4.265; 95% CI, 27.57-62.19). Median overall survival was 7.89 months (SE 0.67; 95% CI, 6.58-9.20) for patients without surgical intervention and 136.61 months (SE 16.44; 95% CI, 104.38-168.84, p < 0.001) for patients who underwent surgery. Increased age (HR, 1.05; 95% CI, 1.03-1.06; p < 0.001), T4 stage disease (HR, 3.17; 95% CI, 1.96-5.1; p < 0.001), NEC-NOS histology (HR, 2.82; 95% CI, 1.64-4.86; p < 0.001), LC-NEC histology (HR, 2.73; 95% CI, 1.04-7.17; p = 0.041) and SC-NEC histology (HR, 5.17; 95% CI, 2.95-9.05; p < 0.001) were all positive predictors of worsening overall survival. The main limitation of the study is its retrospective design.
UNASSIGNED: R-NEN is an aggressive tumour characterized by high mortality rates. Surgery continues to be the mainstay of treatment and has shown to provide a survival benefit for most patients.
UNASSIGNED: R-NEN is composed of several tumour histologies that differ based on their aggressiveness with NEC-NOS and SC-NEC being the most lethal. Surgery, predominantly through minimally invasive approaches, is the mainstay of treatment and has a clear survival benefit.

BACKGROUND: Herein we report a case of an extremely rare pancreatic adenocarcinoma with enteroblastic differentiation (AED), an underrecognized histological subtype. Moreover, the tumor was mixed with a neuroendocrine carcinoma (NEC), which is also a rare malignancy in the pancreas.
METHODS: The patient was an elderly male who was incidentally diagnosed with a 35 mm-sized pancreatic head tumor and underwent pancreatoduodenectomy. Histopathologically, the tumor was composed of four different types: conventional ductal adenocarcinoma, AED, NEC, and squamous cell carcinoma. Interestingly, p53 overexpression and loss of Rb expression, which are characteristic findings of NEC, were observed in all components. He had been received adjuvant chemotherapy after the surgery, however, he died of bath-related cardiac arrest 14 months after surgery.
CONCLUSIONS: In the stomach, AED, a carcinoma resembling fetal gut epithelium, is a rare but established subtype and is considered a related entity of hepatoid carcinoma (HAC). However, gastric AED and HAC differ to some extent. In contrast to the stomach, extragastric AED, including pancreatic AED, is extremely rare, and its biological features are unclear. A mixed tumor with NEC is a complex phenomenon, but it is occasionally reported in extragastric AED. The histogenesis of mixed AED-NEC can be resolved by determining p53 and Rb status.
CONCLUSIONS: Owing to their rare and novel nature, extragastric AED is under-recognized or confused with HAC. Further studies and the establishment of an extragastric AED classification are required.

In this study, we investigate the expression of muscle markers, including the specific skeletal muscle markers myogenin and myoD1, in neuroendocrine carcinomas (NECs). The study included 23 NECs from various sites (14 small cell NECs and 9 large cell NECs). These were stained with desmin, myogenin and myoD1. Positive staining with at least one muscle marker was observed in 14 cases (61%). 8 (35%), 8 (35%) and 11 (48%) of the cases were positive with desmin, myogenin and myoD1 respectively. In most, but not all, cases positive staining was focal generally involving < 10% of tumour cells. Expression of muscle markers is not uncommon in NECs. This represents an important diagnostic pitfall of which pathologists should be aware. In reporting this phenomenon, we speculate on the pathogenesis of this \"aberrant\" expression of muscle markers.

UNASSIGNED: Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied.
UNASSIGNED: The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients\' medical and pathological data were collected and analyzed.
UNASSIGNED: We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142).
UNASSIGNED: Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients\' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.

Neuroendocrine neoplasms (NENs) encompass tumors arising from neuroendocrine cells in various organs, including the gastrointestinal tract, pancreas, adrenal gland, and paraganglia. Despite advancements, accurately predicting the aggressiveness of gastroenteropancreatic (GEP) NENs based solely on pathological data remains challenging, thereby limiting optimal clinical management. Our previous research unveiled a crucial link between hypermethylation of the protocadherin PCDHGC3 gene and neuroendocrine tumors originating from the paraganglia and adrenal medulla. This epigenetic alteration was associated with increased metastatic potential and succinate dehydrogenase complex (SDH) dysfunction. Expanding upon this discovery, the current study explored PCDHGC3 gene methylation within the context of GEP-NENs in a cohort comprising 34 cases. We uncovered promoter hypermethylation of PCDHGC3 in 29% of GEP-NENs, with a significantly higher prevalence in gastrointestinal (GI) neuroendocrine carcinomas (NECs) compared with both pancreatic (Pan) NECs and neuroendocrine tumors (NETs) of GI and Pan origin. Importantly, these findings were validated in one of the largest multi-center GEP-NEN cohorts. Mechanistic analysis revealed that PCDHGC3 hypermethylation was not associated with SDH mutations or protein loss, indicating an SDH-independent epigenetic mechanism. Clinically, PCDHGC3 hypermethylation emerged as a significant prognostic factor, correlating with reduced overall survival rates in both patient cohorts. Significantly, whereas PCDHGC3 hypermethylation exhibited a strong correlation with TP53 somatic mutations, a hallmark of NEC, its predictive value surpassed that of TP53 mutations, with an area under the curve (AUC) of 0.95 (95% CI 0.83-1.0) for discriminating GI-NECs from GI-NETs, highlighting its superior predictive performance. In conclusion, our findings position PCDHGC3 methylation status as a promising molecular biomarker for effectively stratifying patients with GI-NENs. This discovery has the potential to advance patient care by enabling more precise risk assessments and tailored treatment strategies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.