[A Case of Esophageal Cancer with Multiple Lung Metastases Resected after Stent Placement and Chemotherapy].

A 70-year-old man was diagnosed with middle and lower thoracic esophageal squamous cell carcinoma. A computed tomography(CT)scan revealed multiple pulmonary metastases. The clinical stage was T3N1M1, Stage Ⅳb. After esophageal stent placement was performed to alleviate strong stenotic symptoms, cisplatin/5-fluorouracil(CDDP/5-FU)therapy was introduced, and 8 courses were completed. Four additional courses of 5-FU monotherapy were then administered. Following systemic chemotherapy, CT scans showed no evidence of lung metastases. About a year after the initial treatment, the patient underwent a thoracoscopic esophagectomy. Postoperatively, he was followed up without treatment and has remained alive for 1 year and 4 months without any recurrence.

A case of ovarian carcinosarcoma with a germline pathogenic variant of BRCA2 involving a perforated appendix with an abscess.

We report a case of rare and aggressive ovarian carcinosarcoma with a germline pathogenic BRCA2 variant. A patient with a history of breast cancer who developed an inflammatory ovarian tumor with peritonitis carcinomatosis involving the appendix suffered from cachexia. Following three cycles of weekly paclitaxel and carboplatin chemotherapy, emergency surgery was required owing to sepsis. Bilateral salpingo-oophorectomy, total hysterectomy, appendectomy, and small intestine adhesiolysis were performed. Histologically, the tumor comprised an admixture of carcinomatous and sarcomatous components, with involvement of the appendix, which had caused perforation and abscess formation. The final diagnosis was ovarian carcinosarcoma with a germline pathogenic BRCA2 variant, c.658_659del (p.Val220fs). The patient responded completely to adjuvant chemotherapy. A combination of chemotherapy and surgery might be beneficial to patients with ovarian carcinosarcoma and germline pathogenic BRCA2 variants with a poor general condition. This is the first report of ovarian carcinosarcoma with a germline pathogenic BRCA2 variant that responded favorably to chemotherapy.

Clinical Utility of Comprehensive Genomic Profiling in Patients with Unresectable Hepatocellular Carcinoma.

The molecular mechanism of hepatocellular carcinoma (HCC) is partially demonstrated. Moreover, in the patients receiving multiple molecular-targeted therapies, the gene alternations are still unknown. Six molecular-targeted therapies of unresectable HCC (uHCC) and comprehensive genomic profiling (CGP) have been approved in clinical practice. Hence, the utility of CGP in patients with uHCC treated with multiple molecular-targeted agents is investigated. The data of the patients with uHCC who received CGP tests were collected, retrospectively, between February 2021 and May 2022. Gene alterations detected by foundation testing, excluding variants of unknown significance, were reported in all nine patients. The samples for CGP were derived from liver tumor biopsy (n = 2), surgical specimens of bone metastases (n = 2), and blood (n = 5). The median number of systemic therapies was four. Seven patients were candidates eligible for clinical trials. One patient with a high tumor mutation burden (TMB) could receive pembrolizumab after CGP. This study presented genomic alternations after receiving multiple molecular-targeted therapies. However, further investigation needs to be conducted to develop personalized therapies and invent newer agents for treating HCC.

[CASE OF LOW-RISK PROSTATE CANCER WITH LYMPH NODE METASTASIS IN THE ANTERIOR PROSTATIC FAT TISSUE].

A 78-year-old man with a prostate-specific antigen level of 10 ng/mL was referred to our hospital. Magnetic resonance imaging revealed a Prostate Imaging-Reporting and Data System category of 5 in the apex transition zone. Transrectal and transperineal prostate needle biopsies were performed at a total of 20 sites. A well-differentiated adenocarcinoma with a Gleason score of 3+3 was detected on the right peripheral zone of the biopsied specimen. There were no apparent metastases, and robot-assisted radical prostatectomy was performed (Lesion 1: 30 mm lesion with a Gleason score of 4+5, EPE1, RM1, ly0, v0, pn1, sv0 in the bilateral transitional zones; Lesion 2: 4 mm lesion with a Gleason score of 3+3, EPE0, RM0, ly0, v0, pn0, sv0 in the left peripheral zone). Lymph node metastasis was found in the separately submitted anterior prostatic fat tissue. Removal of the anterior prostatic fat tissue is a simple procedure and is considered useful for evaluating the stump, and in this hospital, the tissue is routinely submitted for pathological diagnosis. It is extremely unlikely that lymph nodes will be found in the anterior prostatic fat tissue, and it is even less likely that any lymph node in the tissue will contain lymph node metastases. We therefore report a case of incidental discovery of lymph node metastasis in the anterior prostatic fat tissue at our hospital.

Novel pathologic manifestation of idiopathic massive myocardial calcification.

Idiopathic myocardial calcification is a rare disease. Herein, we report a case of massive idiopathic calcification; a 78-year-old woman presented with acute heart failure with preserved ejection fraction (HFpEF). Computed tomography and magnetic resonance imaging showed diffused calcified nodules in the myocardium. The patient was treated for HFpEF; however, the calcified nodules and diastolic dysfunction gradually progressed. She was hospitalized for heart failure with preserved ejection fraction 6 times before her death at the age of 84 years. The pathological report showed calcified nodules with surrounding collagen fibers in the myocardium and tiny calcifications within the myocytes. Thus, idiopathic myocardial calcification can result in HFpEF, while calcification and diastolic dysfunction can gradually worsen.

Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma.

OBJECTIVES: The diagnostic utility of En1 in the histopathologic differentiation of eccrine porocarcinoma (EPC) from invasive squamous cell carcinoma (SCC) was investigated. METHODS: Expression of En1 and CK19 in 16 cases of EPC was immunohistochemically examined and compared with that in 32 cases of SCC. RESULTS: In all 16 EPCs, En1 was expressed in 3% to 100% of tumor cells. In 20 of the 32 SCCs, En1 was expressed in 3% to 90% of tumor cells. A total of 13 of the 16 EPCs and five of the 32 SCCs were judged as En1 positive, with a cutoff value of 25%. In addition, 11 of the 16 EPCs and four of the 32 SCCs were CK19 positive. The frequencies of En1- and CK19-positive cases were significantly higher in EPCs than in SCCs. In a logistic regression analysis for predicting EPC, En1 and CK19 were independent markers. When expression patterns of En1 and CK19 were combined, none of the 32 SCCs was both positive. In contrast, 15 of the 16 EPCs were positive for either En1 or CK19. CONCLUSIONS: A combination of En1 and CK19 expression can improve the accuracy of histologic diagnosis of EPC.

Disseminated Carcinomatosis of the Bone Marrow from Occult Breast Cancer Responding to a Sequence of Endocrine Therapy.

Patients with cancer of unknown primary (CUP) are generally treated with chemotherapy. Bone marrow involvement suggests an advanced stage, and CUP with disseminated carcinomatosis of the bone marrow (DCBM) appears to have a dismal prognosis. However, our case of CUP with DCBM was successfully treated with a sequence of endocrine therapy over a long period. A woman presenting with low back pain was found to have multiple bone metastasis without an identifiable primary tumor on imaging studies. Blood tests revealed anemia and thrombocytopenia. A bone marrow biopsy was performed and showed relatively uniform small cells, strongly positive for estrogen receptor and progesterone receptor expression. We considered chemotherapy to be risky due to bicytopenia and an aromatase inhibitor, letrozole, was initiated. The patient's symptoms and laboratory findings gradually improved and bone lesions almost disappeared on FDG-PET/CT after 1 year of treatment. After 2 years on letrozole, hemoglobin levels and platelet counts had been gradually decreasing. Although she had no symptoms and no significant changes were observed on a CT scan, disease progression was highly likely. Thus, second-line treatment with fulvestrant and palbociclib was commenced, and hemoglobin levels and platelet counts were restored to within the normal ranges. She currently continues to receive fulvestrant and palbociclib over a year later. CUP complicated with DCBM might be metastatic occult breast cancer, and endocrine therapy can be a valuable treatment option if tumors express hormone receptors.

Non-invasive liver fibrosis assessment correlates with collagen and elastic fiber quantity in patients with hepatitis C virus infection.

AIM: Elastic fiber deposition is a cause of irreversibility of liver fibrosis. However, to date, its relevance to clinical features has not yet been clarified. This study aimed to clarify the correlation between non-invasive markers of fibrosis and fiber quantity, including elastic fiber, obtained from computational analysis. METHODS: This retrospective study included 270 patients evaluated by non-invasive liver fibrosis assessment prior to liver biopsy. Of these patients, 95 underwent magnetic resonance elastography (MRE) and 244 were assessed with Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP). Using whole-slide imaging of Elastica van Gieson-stained liver biopsy sections, the quantity of collagen, elastin, and total fiber (elastin + collagen) was determined. RESULTS: The total fiber quantity showed significant linear correlation with fibrosis stage F0-F4. Collagen fiber quantity increased from stage F0 to F4, whereas elastic fiber quantity increased significantly only from stage F2 to F3. Spearman's rank correlation test revealed that non-invasive liver fibrosis assessment significantly correlates with each fiber quantity, including correlation between total fiber quantity and the Fibrosis-4 (FIB-4) index (r = 0.361, P < 0.001), WFA+ -M2BP values (r = 0.404, P < 0.001), and liver stiffness value by MRE (r = 0.615, P < 0.001). Receiver operating characteristic (ROC) curve analyses revealed that the area under ROC for predicting higher elastic fiber (>3.6%) is 0.731 by FIB-4 index, 0.716 by WFA+ -M2BP, and 0.822 by liver stiffness by MRE. CONCLUSION: Liver fibrosis correlates with fiber quantity through non-invasive assessment regardless of fiber type, including elastic fiber. Moreover, MRE is useful for predicting high amounts of elastic fiber.

A distinctive subgroup of oral EBV+ B-cell neoplasm with polymorphous features is potentially identical to EBV+ mucocutaneous ulcer.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly recognized provisional entity included in mature B-cell neoplasm in the latest 2016 World Health Organization Classification. It has a self-limited growth potential with a high predilection for oral cavities and occurs in age-related or iatrogenic immunodeficiency with indolent clinical courses. However, it shares histological features with EBV-positive diffuse large B-cell lymphoma (DLBCL), and this often leads to diagnostic challenges and controversies in patients with an oral EBV-positive B-cell neoplasm. The aim of this study was to better characterize and comprehend the pathophysiology of DLBCL and EBVMCU in the oral cavity. We conducted clinicopathologic and recurrent gene mutation analysis of 49 cases (14 EBV positive, 35 EBV negative), including cases diagnosed as DLBCL or B-cell lymphoproliferative disorders with high-grade morphology in the oral cavity. All EBV-positive cases matched the criteria of EBVMCU, with significantly earlier clinical stages than the EBV-negative group (P=.0006). Besides, histological analysis showed that all EBV-positive cases presented polymorphous features, whereas 91.4% (32/35) of the EBV-negative cases showed diffuse and monotonous proliferation (P<.0001). Furthermore, EBV-positive cases presented favorable clinical outcomes without disease-related death or recurrence. Gene mutation analysis (MYD88, CD79A, CD79B, CARD11, and EZH2) revealed that 33.3% (9/27) of EBV-negative cases harbored at least 1 gene mutation, whereas no gene mutation was observed in the EBV-positive group (0/11). These results suggest that oral EBV-positive B-cell lymphoid proliferation with polymorphous features often fulfill the criteria for EBVMCU, with clinicopathologically and genetically distinctive properties.

Gastric high-grade dysplasia can be associated with submucosal invasion: evaluation of its prevalence in a series of 121 endoscopically resected specimens.

Gastric neoplasms classified as high-grade dysplasia (HGD) by Western pathologists are frequently diagnosed as tubular adenocarcinoma in Japan. Here, we evaluated the prevalence of submucosal and lymphovascular invasion in a series of 125 endoscopically resected gastric neoplasms. On the basis of Western criteria, the lesions were classified as poorly cohesive carcinomas (n=4) (excluded from further analysis), low-grade dysplasia (n=4), pure HGD (n=78), HGD with tubular adenocarcinoma (n=4), and pure tubular adenocarcinoma (n=35). Submucosal invasion was found in 3.8% of the 78 HGDs, 75.0% of the 4 HGDs combined with adenocarcinoma, and 11.4% of the 35 adenocarcinomas. Venous invasion was detected in 1.3% of the 78 HGDs, 75% of the 4 HGDs combined with adenocarcinoma, and none of the 35 tubular adenocarcinomas. Lymphatic invasion was absent in HGD but noted in 25% of the HGDs combined with adenocarcinoma, and 2.9% of the tubular adenocarcinomas. Thus, we demonstrated that lesions characterized as HGD on the basis of Western criteria can be associated with submucosal and lymphovascular invasion. Endoscopic therapy has made it less crucial to differentiate between HGD and intramucosal adenocarcinoma in biopsy samples of small tubular neoplasms. However, it is important to recognize that the criteria for dysplasia currently used in the West may understate the degree of malignant potential. To limit any diagnostic discrepancy between biopsy, endoscopic resection, and surgical specimens, it is suggested that the features of HGD and adenocarcinoma be reevaluated, which may result in some lesions being classified as mucosal adenocarcinoma.

Significant association between hypolipoproteinemia(a) and lifetime risk of cancer: an autopsy study from a community-based Geriatric Hospital.

BACKGROUND: Our recent study showed that a low lipoproteinemia(a) [Lp(a)] level was a risk factor for cancer and all-cause deaths. The purpose of this study was to verify the role of the Lp(a) level on cancer among consecutive autopsy cases. METHODS: The subjects consisted of 1354 cases (775 men and 579 women). The average age at death was 79.9 years. Hypolipoproteinemia(a) was defined as an Lp(a) level of below 80 mg/L. Overall, 62.3% of the subjects had suffered from at least one to a maximum of five malignancies throughout their lives. The most frequent type of malignancy was gastric cancer, followed by leukemia, lung cancer, and colon cancer. RESULTS: The cancer-bearing status decreased linearly according to the Lp(a) level in both men and women (P=0.01 and P<0.001, respectively). The median Lp(a) level was significantly lower among the cases with hepato-biliary-pancreatic cancers or hematopoietic malignancy, but was higher among cases with lung cancer, especially lung adenocarcinoma. Hypolipoproteinemia(a) was a significant risk factor for any origins of cancer, with an odds ratio of 1.94 (95% CI, 1.45-2.60; P<0.001). It was also a risk factor for hepato-biliary cancers and leukemia, but it was a protective factor for lung cancer. CONCLUSIONS: Our findings suggested hypolipoproteinemia(a) would be a significant risk factor for cancer except lung cancer. This study complements our previous study showing that hypolipoproteinemia(a) would increase the lifetime risk of cancer other than lung cancer.

[A case of pathologically complete response in a patient with locally advanced sigmoid colon cancer after chemotherapy including bevacizumab/FOLFOX4].

A 65-year-old man complaining of abdominal pain was admitted to our hospital. A diagnosis of colon ileus due to sigmoidal colon cancer was made. A stoma was created at the transverse colon, and elective surgery was scheduled. During the operation, the tumor was found to have invaded the bladder and the pelvic wall, making curative resection impossible. Chemotherapy consisting of bevacizumab/oxaliplatin, Leucovorin, and 5-fluorouracil(FOLFOX4, intravenous drip infusion every 2 weeks)was started. After 12 courses of treatment, remarkable shrinkage of the tumor was noted, which led us to perform a sigmoidectomy and partial resection of the bladder wall. A histopathological study of the surgically resected specimen showed no cancer cells. Recovery was uneventful and the patient was discharged on the 17th postoperative day. In cases of advanced colon cancer, complete response of the primary tumor with preoperative chemotherapy is very unusual. We conclude that chemotherapy with bevacizumab/FOLFOX4 plays a role in the management of advanced/unresectable colon cancer.

Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach.

BACKGROUND: Microsatellite instability (MSI) has been observed in 8-39 % of sporadic gastric cancers. However, despite numerous reports indicating a significant relationship between intestinal-type histology and MSI, detailed correlation between histological subtypes and MSI remains obscure. The purpose of the present study is to clarify the relationship between histological subtype and microsatellite status in gastric carcinomas. METHODS: Microsatellite status was examined for 464 consecutive gastric carcinomas from 420 patients as well as histological subtypes and other clinicopathological findings. RESULTS: MSI was observed in 82 carcinomas (17.7 %), and the greatest proportions were observed in solid-type, poorly differentiated adenocarcinoma (43.0 %) and papillary adenocarcinoma (32.5 %), both being significantly higher than those of other subtypes. The proportion increased with advancing age (0 % at 51-64 years, 8.5 % at 65-74 years, 18.4 % at 75-84 years, 35.3 % at 85-96 years). Compared with microsatellite-stable carcinomas, microsatellite-unstable carcinomas were significantly related with older age, female gender, antral location, and predominant papillary adenocarcinoma and solid-type, poorly differentiated adenocarcinoma. Poorly differentiated type carcinoma was significantly less frequent than differentiated type in microsatellite-unstable cancer at the early stage, whereas no significant difference existed at the advanced stage. CONCLUSIONS: These results suggest that there are specific histological subtypes with highly frequent MSI and that gastric carcinoma with MSI originates from differentiated-type carcinomas, indicating histological diversity during tumor growth.

[Pathologic characteristics of malignant neoplasms occurring in the elderly].

Malignant neoplasms usually occur in the elderly. Common cancers in elderly men are gastric, lung, colorectal and prostate, whereas they are colorectal, gastric, lung and biliary in elderly women. Compared with malignant neoplasms in younger patients, several characteristic features exist in the neoplasms of the elderly, such as tumor location, histology, biological behavior, and the pathway of tumor carcinogenesis. The incidence of multiple cancers increases with aging. Although it is generally recognized that carcinoma in the elderly is well -differentiated and shows slow growth, a low incidence of metastases and favorable prognoses, tumors do not always evidence such features. Regarding biological behavior of malignant tumors in the elderly, age-related alterations of the host, such as stromal weakness and decreased immune response against cancer cell invasion should be considered, as well as the characteristics of the tumor cell itself.

Diagnostic possibility of diffusion tensor imaging for the evaluation of myometrial invasion in endometrial cancer: an ex vivo study.

PURPOSE: To investigate the feasibility of magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) for evaluating the myometrial invasion of uterine endometrial cancer. MATERIALS AND METHODS: Twelve specimens of uterine endometrial cancer were obtained. The depth of myometrial invasion was classified as stage E (limited to the endometrium; n = 4), stage S (superficial invasion of less than 50% of the myometrium; n = 5), or stage D (deep invasion of greater than 50% of the myometrium; n = 3). The specimens were fixed in 10% formalin and stored at 4°C before imaging. At 15 hours after fixation, MRI was performed using a 4.7-T experimental imager/spectrometer system. RESULTS: We found a high fractional anisotropy (FA) value zone (anisotropic zone) at the myometrium adjacent to the tumor on FA maps of histopathological stage S and stage D cancers, whereas the anisotropic zone did not exist in stage E cancers. Histopathological analysis showed that compared to the other regions, the anisotropic zone had tightly packed stromal tissue. The disruption of the anisotropic zone was consistent with myometrial invasion. CONCLUSION: Our ex vivo study suggests that DTI might be a useful tool for the diagnosis of myometrial invasion of uterine endometrial cancer ex vivo.