The potential of COVID-19 patients' sera to cause antibody-dependent enhancement of infection and IL-6 production.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many vaccine trials have been initiated. An important goal of vaccination is the development of neutralizing antibody (Ab) against SARS-CoV-2. However, the possible induction of antibody-dependent enhancement (ADE) of infection, which is known for other coronaviruses and dengue virus infections, is a particular concern in vaccine development. Here, we demonstrated that human iPS cell-derived, immortalized, and ACE2- and TMPRSS2-expressing myeloid cell lines are useful as host cells for SARS-CoV-2 infection. The established cell lines were cloned and screened based on their function in terms of susceptibility to SARS-CoV-2-infection or IL-6 productivity. Using the resulting K-ML2 (AT) clone 35 for SARS-CoV-2-infection or its subclone 35-40 for IL-6 productivity, it was possible to evaluate the potential of sera from severe COVID-19 patients to cause ADE and to stimulate IL-6 production upon infection with SARS-CoV-2.

Coexistence of gastric cancer and gastric GIST with intra-tumor bleeding: successful embolization with subsequent total gastrectomy.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a rare tumor, however, simultaneous development of gastric cancer and gastric GIST has been documented more frequently in recent years. Rupture of gastric GIST is even more rare and occurred in 7% of all GISTs. Although ruptured GIST might be occasionally difficult to be managed by endoscopy, transcatheter arterial embolization (TAE) was reported to control bleeding from GIST effectively. We report herein a case of coexistence of gastric cancer and gastric GIST with progressing intra-tumor bleeding managed successfully by TAE and review the clinicopathological characteristics of this rare condition reported previously in the Japanese literature. CASE PRESENTATION: A 75-year-old woman with dyspnea and systemic edema was diagnosed as simultaneous occurrence of gastric cancer (histopathologically detected tubular adenocarcinoma pT2N1M0 fStageIIA) and gastric GIST (65 × 92 mm in diameter at the anterior wall of the fornix) with intra-tumor hemorrhage. Perceiving the progress of bleeding from tumor growth and exacerbating anemia, TAE of left gastric artery was performed. Then remission of anemia has been obtained, the patient underwent an elective radical surgery. CONCLUSIONS: Simultaneous occurrence of gastric cancer and gastric GIST was speculated to be more common. TAE for ruptured GIST may be effective for hemostasis and reduction of tumor burden, which could facilitate minimal invasive surgery.

Hyalinized stroma is a characteristic feature of pancreatic intraductal oncocytic papillary neoplasm: An immunohistochemical study.

Hyalinized stroma (HS) is a dense, eosinophilic, and amorphous extracellular material in the stroma. HS is observed in several tumors; however, it has not been comprehensively studied in pancreatic intraductal papillary mucinous neoplasm (IPMN) or intraductal oncocytic papillary neoplasm (IOPN). Here, we aimed to evaluate the immunohistochemical and microscopic characteristics of HS in IPMN and IOPN. The prevalence of HS was determined in 168 cases of IPMN, including intestinal type (IPMN-I), gastric type (IPMN-G), and pancreatobiliary type (IPMN-PB), as well as in 11 cases of IOPN. Immunohistochemical staining for laminin and collagen (types I, II, III, IV, and V), as well as Congo red staining were performed in IPMN and IOPN cases containing HS. The prevalence of HS among the IPMN and IOPN specimens was 1.2% (2/168 cases) and 45.5% (5/11 cases), respectively. The prevalence rates of HS in each IPMN subtype were as follows: 2.2% (2/91 cases) in IPMN-G, and 0% in IPMN-PB and IPMN-I. All seven HS cases were positive for collagen I, III, IV, and V but were negative for Congo red staining. Most cases showed negative, focal, or weak expression of laminin and type II collagen. These findings indicate that HS is associated with IOPN and is primarily composed of collagen fibers.

Conversion surgery for an initially unresectable, locally advanced pancreatic cancer after induction chemotherapy and carbon-ion radiotherapy: a case report.

BACKGROUND: Pancreatic cancer has a very high mortality rate worldwide, and about 30-40% of all patients have extensive vascular involvement at initial diagnosis that precludes surgical intervention. Here, we describe our experience in a patient with locally advanced pancreatic cancer (LAPC) who underwent R0 conversion surgery after undergoing a combination of chemotherapy and carbon-ion radiotherapy (CIRT), which led to long-term relapse-free survival (23 months). CASE PRESENTATION: A 41-year-old woman presented a month ago with epigastralgia referred to our facility and was subsequently diagnosed with pancreatic cancer cStage III (Ph, TS2 (35 mm), cT4, cCH1, cDU1, cS1, cRP1, cPL1, cVsm0, cAsm1, cN0, cM0) that was also categorized as an unresectable LAPC. She immediately underwent 3 cycles of induction chemotherapy (gemcitabine + nanoparticle albumin-bound (nab-) paclitaxel) followed by CIRT with concurrent gemcitabine. Although significant shrinkage of the primary tumor occurred, frequent cholangitis due to duodenal stenosis of unknown etiology prevented continued chemotherapy, and 9 months after the first visit, she underwent a radical, subtotal, stomach-preserving, pancreaticoduodenectomy (SSPPD). Histopathologic examination of the resected tissue revealed a R0 resection with a histological response of Evans grade IIB. She was administered an almost full dose of S-1 as adjuvant chemotherapy for 6 months and has shown no signs of recurrence in 23 months. CONCLUSIONS: We report a first case of successful conversion surgery for an initially unresectable LAPC after rapid induction GEM + nab-PTX chemotherapy followed by CIRT. Rapid induction GEM + nab-PTX chemotherapy followed by CIRT for LAPC might be a safe and effective treatment option.

Rectal Neuroendocrine Tumor with Synchronous Pancreatic Metastasis: A Case Report.

INTRODUCTION: Gastrointestinal neuroendocrine tumors (GI-NETs) often show hematogenous metastasis, with the liver being the most common metastatic site; however, metastasis to the pancreas is rare. CASE PRESENTATION: We report a rare case of rectal NETs with pancreatic metastases in a 75-year-old man who presented with a chief complaint of constipation. Imaging and endoscopic findings revealed a rectal submucosal tumor, a pancreatic hypovascular mass, and multiple liver masses. The rectal lesion and pancreatic lesions were diagnosed as neuroendocrine tumors using biopsy and endoscopic ultrasound fine-needle aspiration, respectively. Synchronous rectal NET and pancreatic NET (P-NET) with liver metastasis of either of these two were preoperatively diagnosed. A two-stage surgery was performed, comprising abdominoperineal resection and distal pancreatectomy. Pre-operative imaging findings showed a solitary mass in the pancreas, although the resected specimen contained multiple lesions. Immunohistochemical staining of the resected rectal and pancreatic lesions showed that both were synaptophysin positive and chromogranin A (CgA) negative. Generally, rectal NET cells are positive for synaptophysin and negative for CgA, while the majority of P-NETs are positive for both. The final diagnosis was rectal NETs with pancreatic and liver metastases. Till date, there have been no reports on the outcomes in patients with pancreatic metastasis of GI-NETs. CONCLUSIONS: More case reports on metastatic NETs are needed to arrive at a consensus for a standardized treatment regimen.

Nectin-1 expression in cancer-associated fibroblasts is a predictor of poor prognosis for pancreatic ductal adenocarcinoma.

PURPOSE: Nectin-1 is a cell adhesion molecule that regulates the formation of adherens junctions and tight junctions. We measured the expression of nectin-1 in cancer-associated fibroblasts (CAFs) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Nectin-1 expression was measured via immunohistochemistry using tissue microarray blocks constructed from resected PDAC tissue from 258 patients. We screened for associations between nectin-1 expression and clinicopathological parameters. According to the percentage of CAFs stained, expression was classified as negative at ≤ 30% and positive at > 30%. RESULTS: Nectin-1 expression was confirmed in CAFs from 64 patients (24.8%), and was associated with lymph node metastasis (p = 0.016), advanced Union for International Cancer Control stage (p = 0.016), perineural invasion (p = 0.022), pancreatic head tumors (p = 0.023), and shorter overall survival (p = 0.003). Multivariate analysis revealed that nectin-1 expression in CAFs was an independent prognostic factor (p = 0.038). CONCLUSIONS: Diffuse nectin-1 expression in the CAFs of PDAC patients is associated with invasion, metastasis, and shorter survival.

Epidermoid cysts are a characteristic feature of intrapancreatic but not of extrapancreatic accessory spleens.

Accessory spleens (ASs), ectopic splenic tissue at intrapancreatic and extrapancreatic sites, rarely contain epidermoid cysts. Our aim was to analyze the incidence of epidermoid cysts in ASs and perform an immunohistochemical analysis of its epithelial lining. We included in the study 148 ASs from 135 patients, for which pathological data were available. Eleven were intrapancreatic ASs (IPASs) and 137 were extrapancreatic ASs (EPASs). Six of the eleven (55%) IPASs contained epidermoid cysts, but they were not detected in EPASs. Immunohistochemical analysis showed that both the superficial/luminal and basal layer of the epithelial lining of epidermoid cysts in IPASs are negative for MUC2, MUC5AC, MUC6, WT-1, calretinin, thrombomodulin, uroplakin-II, and uroplakin-III. The superficial/luminal layer was positive for MUC4, CK7, and CA19-9 in all cases (100%), for CEA and HBME-1 in three cases (50%), and for MUC1, CK5/6, and CK20 in two cases (33%). The superficial/luminal layer was negative for p63 and D2-40 in all cases. The basal layer was positive for MUC1, CK5/6, p63, and HBME-1 in all six cases (100%), for CK7 and D2-40 in two cases (33%), and for CEA in one case (17%). The basal layer was negative for MUC4, CK20, and CA19-9 in all cases. Epidermoid cysts are a characteristic feature of IPASs but not of EPASs. Immunohistochemical analysis showed that the epithelial lining of epidermoid cysts in IPASs has a mixed character of glandular, squamous, mesothelial, and urothelial epithelium.

A Serous Cystic Neoplasm of the Pancreas Coexisting with High-Grade Pancreatic Intraepithelial Neoplasia Mimicking an Intraepithelial Papillary Mucinous Neoplasm: A Case Report.

Serous cystic neoplasms of the pancreas are rare exocrine pancreatic neoplasms, most of which are benign and do not communicate with the pancreatic duct. Pancreatic intraepithelial neoplasm (PanIN) is considered a precursor of ductal adenocarcinoma that is microscopically recognized in pancreatic ducts. A 67-year-old Japanese woman presented with a 10-mm multilocular cystic lesion at the pancreatic body. Magnetic resonance pancreatography showed stenosis of the main pancreatic duct at the pancreatic body and dilatation of the distal side of the main pancreatic duct. Furthermore, communication between the cystic lesion and the main pancreatic duct was suspected based on magnetic resonance pancreatography findings. Distal pancreatectomy was performed under the preoperative diagnosis of intraductal papillary mucinous neoplasm. Histologically, the cystic lesion was lined with a non-atypical cuboidal or flat epithelium with clear cytoplasm and was thus diagnosed as a serous cystic neoplasm. High-grade PanIN lesions with stromal fibrosis were observed at the main and branch pancreatic ducts. Histological examination revealed no communication between the serous cystic neoplasm and the pancreatic ducts. Immunohistochemically, the epithelium of the serous cystic neoplasm showed positive anti-von Hippel-Lindau antibody staining, whereas the epithelium of the PanIN showed negative staining. A serous cystic neoplasm coexisting with another pancreatic neoplasm is rare. When dilatation of the main or branch pancreatic ducts coexists with a serous cystic neoplasm, as in this case, the lesion clinically mimics an intraductal papillary mucinous neoplasm.

Laparoscopic splenopancreatectomy for an endocrine tumor with cystic changes: a case report.

The biological behavior of a cystic pancreatic endocrine neoplasm is less aggressive than that of pancreatic neuroendocrine neoplasms, and its prognosis is better. Limited surgery should be considered for cystic pancreatic endocrine neoplasms that are not accompanied preoperatively by lymph node or distant metastasis.

Undifferentiated carcinoma of the ampulla of Vater.

Undifferentiated carcinoma of the ampulla of Vater is a rare disease with unclear and clinical characteristics and prognosis. Here, we report the case of a 61-year-old man with undifferentiated carcinoma of the ampulla of Vater. He presented to our hospital with an increase in hepatobiliary system enzymes that was detected during a health check-up. Imaging and endoscopy demonstrated a tumor with ulcer in the ampulla of Vater, which was diagnosed as a carcinoma by biopsy. No distant metastasis was observed. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Undifferentiated carcinoma was confirmed based on the presence of small round atypical cells with the formation of a solid alveolar lesion on histopathological examination and immunohistochemical staining that was positive for CAM 5.2 but negative for chromogranin A and synaptophysin. The tumor infiltrated the duodenum, but not the pancreas; no lymph node metastasis was observed. However, liver metastases were detected 2 months postoperatively. Chemotherapy was performed, and the tumor size temporality decreased; however, it grew in size again, and the patients subsequently died of the primary disease 15 months postoperatively. Undifferentiated carcinoma of the ampulla of Vater is a very rare histological type. More number of cases is necessary to clarify optimal treatment.

Clinicopathological significance of Necl-4 expression in pancreatic ductal adenocarcinoma.

AIMS: The loss, or decreased expression, of nectin-like molecule 4 (Necl-4; an immunoglobulin-like cell adhesion molecule) is reported to be associated with the development and progression of certain types of cancer. We investigated the clinicopathological significance of Necl-4 expression in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Immunohistochemical analyses of Necl-4 (n=258) and E-cadherin (n=256) expression were performed using tissue microarray blocks of PDAC samples. Necl-4 expression of 38 pancreatic intraepithelial neoplasia (PanIN) lesions included in tissue microarray cores was also evaluated. Necl-4 and E-cadherin expression was considered positive if >30% of cells were stained, and negative if ≤30% of cells were stained. RESULTS: Necl-4 expression was positive in 45.7% (n=118) and negative in 54.3% (n=140) of PDAC cases. Necl-4 staining was positive in 96.7% (n=29) and negative in 3.3% (n=1) of low-grade PanIN cases, and positive in 62.5% (n=5) and negative in 37.5% (n=3) of high-grade PanIN cases. The number of cases with positive Necl-4 expression decreased in the order low-grade PanIN>high-grade PanIN>PDAC (p<0.001). Negative Necl-4 expression was significantly associated with a larger tumour size of >30 mm, perineural invasion, lymphatic involvement, lymph node metastasis (pN1), an advanced TNM (tumour, node, metastases) stage (stage IIB-IV), an advanced histological grade (G2/3), and shorter overall survival. E-cadherin staining was positive in 46.1% (n=118) and negative in 53.9% (n=138) of PDAC cases. Necl-4 expression correlated positively with E-cadherin expression (r=0.405, p<0.001). CONCLUSIONS: The results suggest that Necl-4 is associated with carcinogenesis and aggressiveness of PDAC.

Carcinosarcoma of the ampulla of Vater: a case report and literature review.

BACKGROUND: Carcinosarcoma of the ampulla of Vater is extremely rare, and to the best of our knowledge, this is the third reported study. CASE PRESENTATION: The patient was a 73-year-old man, who presented with a chief complaint of dark urine. After a work-up, we suspected duodenal papillary cancer and performed a subtotal stomach-preserving pancreaticoduodenectomy with lymph node dissection. Immunohistochemically, the sarcomatous atypical cells were diffusely positive for cytokeratin AE1&3 and vimentin and focally positive for α-smooth muscle actin; these cells were also negative for desmin, CD34, DOG1, c-kit, and S100. From these findings, we diagnosed the patient with so-called carcinosarcoma. There was no lymph node metastasis. CONCLUSIONS: Carcinosarcoma of the ampulla of Vater has a poor prognosis, and lymph node metastases are often seen. For the complete cure of carcinosarcoma of the ampulla of Vater, resection with the dissection of the lymph nodes may be necessary.

Cholangiolocellular Carcinoma of the Liver Exhibiting High F-18 FDG Uptake.

Cholangiolocellular carcinoma (CoCC) is a rare primary liver cancer. It is considered to originate from hepatic progenitor or stem cells. We report a rare case of a 74-year-old male with CoCC of the liver and duodenal gastrointestinal stromal tumor (GIST). Both tumors manifested tracer uptakes on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT); however, the uptake in hepatic tumor was extremely higher than that in the duodenal tumor. This finding was helpful to exclude the metastasis of GIST.

Bone morphogenetic protein-2 expression in an intraductal papillary mucinous neoplasm with marked ossification: A case report.

Intratumoral ossification has been reported in a number of epithelial tumors, but its presence in intraductal papillary mucinous neoplasms (IPMNs) is very rare. Herein, we present a rare case of IPMN with marked ossification. A 56-year-old Japanese man was under follow-up for a previously diagnosed IPMN. Seven years later, he was found to have dilatation of the main pancreatic duct and an enlarged solid mass, for which pancreaticoduodenectomy was performed. Macroscopically, multiple and cystically dilated pancreatic branch ducts, as well as a dilated main pancreatic duct, were identified. There was a solid, polypoid hard mass measuring 15 × 12 mm in the cystically dilated branch of the duct in the pancreatic head. Histological examination revealed papillary proliferation of atypical cuboidal or columnar epithelial cells in the dilated main and branch pancreatic ducts. The solid mass included an invasive adenocarcinoma component with a tubular or trabecular structure that showed pronounced ossification. We diagnosed the patient with invasive IPMN accompanied by marked ossification. Immunohistochemically, tumor cells in both the non-invasive and invasive lesions expressed bone morphogenetic protein-2 (BMP-2). While the mechanism of intratumoral ossification is unclear, it may have involved BMP-2 in the present case.

Bile duct carcinoma associated with congenital biliary dilatation in a 16-year-old female: a case report and literature review.

We encountered a very rare case of bile duct carcinoma associated with congenital biliary dilatation (CBD) in a 16-year-old female who was admitted to our hospital because of right upper abdominal pain and vomiting. Abdominal computed tomography demonstrated a cystic dilatation of the common bile duct measuring 7 cm in diameter and two enhanced tumors 4 cm in diameter located in the inferior bile duct and middle bile duct. Magnetic resonance cholangiopancreatography clearly demonstrated a cystic dilatation of the extrahepatic bile duct (Todani's CBD classification: type 4-A). Endoscopic retrograde cholangiopancreatography also revealed two tumors. Biopsy results of one of the tumors confirmed adenocarcinoma. Excision of the perihilar bile duct and subtotal stomach-preserving pancreaticoduodenectomy with dissection of the major lymph nodes were performed. A postoperative histopathologic examination revealed a well-differentiated tubular adenocarcinoma, which remained within the mucosal layer, and no lymph node metastasis was found. The postoperative course was uneventful, and the patient was discharged 10 days after surgery and has remained disease-free for 21 months.

Molecular alterations in sporadic pancreatic neuroendocrine microadenomas.

BACKGROUND: Pancreatic neuroendocrine microadenomas (pNEMAs) are neuroendocrine tumors measuring <5 mm in diameter. They are considered the precursor of pancreatic neuroendocrine tumors (pNETs). The aim of this study was to investigate the immunohistochemical differences between pNEMA, pNET, and hyperplasia of pancreatic islet cells (HPIL) in patients with non-familial syndromes. METHODS: We evaluated 21 pNEMAs, 19 HPILs, and 21 non-functional pNETs (10 G1 and 11 G2 cases) in patients with non-familial syndromes. Immunohistochemistry for tumor-associated markers death domain-associated protein (DAXX), alpha thalassemia/mental retardation X-linked (ATRX), cytokeratin 19 (CK19), bcl-2, and CD99 was performed. RESULTS: DAXX was expressed in 95%, 71%, and 71% of HPIL, pNEMA, and pNET samples, respectively; the differences were not significant. ATRX expression in pNEMA and pNET was significantly lower than that in HPIL, whereas there was no significant difference between pNEMA and pNET (HPIL: 95%, pNEMA: 43%, and pNET: 52%). All HPIL and pNEMA cases were negative for bcl-2 and positive for CD99, whereas 29% of pNETs were positive for bcl-2 and 24% were negative for CD99. CK19 expression in HPIL was significantly lower than in pNEMA and pNET, although no significant difference was observed between pNEMA and pNET (HPIL: 5%, pNEMA: 57%, and pNET: 43%). Among G1 and G2 pNETs, CD99 was expressed in 50% of G1 pNETs but not in any G2 pNET cases. CONCLUSION: Non-familial HPIL, pNEMA, and pNET patients exhibit distinct ATRX, CD99, CK19, and bcl-2 molecular profiles.

Danger peptide receptor signaling in plants ensures basal immunity upon pathogen-induced depletion of BAK1.

Pathogens infect a host by suppressing defense responses induced upon recognition of microbe-associated molecular patterns (MAMPs). Despite this suppression, MAMP receptors mediate basal resistance to limit host susceptibility, via a process that is poorly understood. The Arabidopsis leucine-rich repeat (LRR) receptor kinase BAK1 associates and functions with different cell surface LRR receptors for a wide range of ligands, including MAMPs. We report that BAK1 depletion is linked to defense activation through the endogenous PROPEP peptides (Pep epitopes) and their LRR receptor kinases PEPR1/PEPR2, despite critical defects in MAMP signaling. In bak1-knockout plants, PEPR elicitation results in extensive cell death and the prioritization of salicylate-based defenses over jasmonate-based defenses, in addition to elevated proligand and receptor accumulation. BAK1 disruption stimulates the release of PROPEP3, produced in response to Pep application and during pathogen challenge, and renders PEPRs necessary for basal resistance. These findings are biologically relevant, since specific BAK1 depletion coincides with PEPR-dependent resistance to the fungal pathogen Colletotrichum higginsianum. Thus, the PEPR pathway ensures basal resistance when MAMP-triggered defenses are compromised by BAK1 depletion.

Positive Intraoperative Peritoneal Lavage Cytology is a Negative Prognostic Factor in Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Study.

OBJECTIVE: The aim of this study is to evaluate the prognostic significance of intraoperative peritoneal lavage cytology (PLC) in pancreatic invasive ductal adenocarcinoma. METHODS: Intraoperative PLC was evaluated in 162 patients with resectable pancreatic invasive ductal adenocarcinoma. The results were analyzed for correlations with clinicopathological parameters and/or prognoses. RESULTS: In the 162 cases of resectable pancreatic ductal adenocarcinoma, 18 (11%), 141 (87%), and 3 (2%) were positive, negative, and equivocal for intraoperative PLC, respectively. Intraoperative PLC positivity was associated with older patients (over 65 years), large tumor size (over 35 mm), tumor location in the body/tail of the pancreas, and distant metastasis. Univariate analysis showed that larger tumor sizes (≥35 mm, P = 0.001), lymph node metastases (P = 0.005), distant metastasis (P = 0.004), advanced stage (stage IIB or III, P = 0.006), advanced tumor histological grade (G3, P < 0.001), or positive intraoperative PLC (P = 0.002) are associated with a shorter survival. Multivariate analysis revealed that larger tumor sizes (≥35 mm, P = 0.026), lymph node metastasis (P = 0.021), advanced tumor histological grade (G3, P < 0.001), and positive intraoperative PLC (P = 0.002) were independent prognostic factors. CONCLUSION: Intraoperative PLC is an independent prognostic factor for resectable pancreatic invasive ductal adenocarcinoma.

Sex differences in immunohistochemical expression and capillary density in pancreatic solid pseudopapillary neoplasm.

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm. Solid pseudopapillary neoplasm is rare in men, and most SPN cases are in young women. This study aimed to investigate sex differences in SPN clinical histopathology including capillary density and expression of immunochemical markers, including glypican 3. A total of 22 resected tumors from pancreatic SPN patients, including 16 women (73%) and 6 men (27%), were analyzed histopathologically and immunohistochemically for synaptophysin, ß-catenin, estrogen receptor, progesterone receptor, Ki-67, CD10, CD31, and glypican 3. The median age was 52.5 years in men and 24 years in women (P = .046). The median tumor size was 22.5 mm in men and 40 mm in women (P = .337). In 11 of the 16 women (69%), but in none of the men, tumors showed complete or incomplete fibrous cap`sules (P = .006). Cholesterol clefts were observed in tumors from 10 women (63%) but in none from the men (P = .012). No significant sex differences were noted in tumor characteristics, including size, macroscopic cystic degeneration, necrosis, lymphovascular involvement, and perineural invasion. The SPNs were weakly positive for glypican 3, although there was no significant difference between sexes. Capillary density tended to be lower in tumors from men than in those from women, but not significantly. Thus, except for the fibrous capsule and cholesterol clefts often found in tumors and the younger age of the women, there were no significant sex differences in histopathologic or immunohistochemical features of SPN, despite its markedly higher occurrence in women.