A case of diverticulum of the appendiceal base resembling a submucosal tumor of the cecum under colonoscopy: a hitherto undescribed lesion.

BACKGROUND: Diverticulosis of the appendix is an uncommon clinical entity, and a preoperative diagnosis is often difficult. Herein we report an unusual case of appendiceal diverticulosis. CASE PRESENTATION: A 72-year-old male was referred to our hospital to examine the cause of hematochezia. A colonoscopy study showed a protruding lesion resembling a submucosal tumor (SMT), approximately 20 mm in diameter, at the site around the appendiceal orifice of the cecum. An abdominal computed tomography and magnetic resonance imaging showed a cystic lesion at the appendiceal base. The lesion was clinically diagnosed as a cystic tumor of the appendix, but the possibility of a malignant tumor could not be excluded. Therefore, a laparoscopic ileocecal resection with lymph node dissection was performed. The pathological examination of the resected specimen revealed that the lesion was a diverticulum (pseudodiverticulum) occurring solitarily at the appendiceal base, in which the mucosal layer of the appendix was invaginated into the submucosa of the adjacent cecum, thus forming an SMT-like lesion. CONCLUSION: To our knowledge, this is the first case report in the English literature showing that an appendiceal diverticulum can manifest as an SMT-like lesion in the cecum. This condition should be recognized as a differential diagnosis for such lesions.

Possible spontaneous regression of hepatocellular carcinoma with unique histopathological features confirmed by surgical resection: a case report.

BACKGROUND: Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event, and its clinicopathological features and underlying mechanism are not fully understood. CASE PRESENTATION: An 84-year-old female with hepatitis C virus infection and diabetes mellitus was referred to our hospital for further examination. Abdominal ultrasonography showed a 3.4-cm solid tumor with a heterogeneous irregular center and no fibrous capsule in liver segment 8 (S8). An enhanced computed tomography (CT) scan revealed a tumor in S8 with heterogeneous enhancement in the arterial phase and washed out insufficiently in the portal and equilibrium phase. The enhanced pattern on magnetic resonance imaging was similar to that of CT. Although the imaging findings were not typical for HCC, liver resection (S8) was performed with HCC as the most probable diagnosis. Histopathological examination of the resected specimen showed that the tumor was well to moderately differentiated HCC with unique features. Approximately half of the tumor was composed of well-differentiated HCC that was focally accompanied by dense lymphocyte infiltration. The other half of the tumor was fibrotic tissue that resembled an inflammatory pseudotumor. Several foci of moderately differentiated HCC were scattered within the tumor with a nodule-in-nodule appearance, and the foci totally showed coagulative necrosis. On immunostaining, lymphocytes in the tumor stroma were positive for CD8 and programmed death 1. The expression of programmed death-ligand 1 was observed in carcinoma cells and macrophages specifically within the lymphocyte-rich area of HCC. CONCLUSIONS: We consider this case representative of spontaneous regression of HCC, and the immune response against HCC might contribute to tumor regression, leading to complex histopathological appearances. This case may provide insight into the mechanism of spontaneous regression of HCC.

Does cellular senescence play an important role in the prognosis of sarcomatoid carcinoma of the pancreas?

AIM: Sarcomatoid carcinoma of the pancreas (SCP) is an extremely rare and aggressive disease with poor prognosis. We have already reported a rare case of SCP with long-term survival. In the present article, we investigate the underlying mechanisms of patient's long-term survival from the point of view of cellular senescence which was examined in three SCP cases, including our reported case, using immunohistochemical analysis. FINDINGS: The expressions of cellular senescence marker were observed in the sarcomatous component of the patient with long-term survival but not observed in the other patients with short- term survival. Thus, we can speculate that cellular senescence might play an important role in the reduction of the cell proliferative and metastatic activities of sarcomatous cells, leading to long-term patient survival.

Heterotopic ossification in lymph node metastasis after rectal cancer resection: a case report and literature review.

BACKGROUND: Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear. CASE PRESENTATION: An 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-ß1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7. CONCLUSION: This is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.

Efficacy of Long-Term Adjuvant Therapy With Imatinib Mesylate After Extensive Surgical Treatment for Ruptured Gastrointestinal Stromal Tumors of the Small Intestine With Peritoneal Metastases: A Case Report.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Although most patients with advanced GISTs benefit from imatinib mesylate (IM) as standard targeted therapy, the optimal duration of adjuvant IM for GIST patients with high risk of recurrence who underwent surgical resection remains unknown. In this article, we present a case of a ruptured GIST of the small intestine accompanied by peritoneal metastases, which was effectively treated by surgical procedure followed by long-term adjuvant therapy with IM. Surgical resection was performed for the ruptured small intestinal GIST, and multitude of peritoneal metastases were cauterized. The patient received adjuvant therapy with IM (400 mg/day) for 12 years without an interruption or a dose change. Peritoneal metastatic recurrence was observed by the follow-up computed tomography scan obtained 12 years after surgery, and surgical resection of the recurrent GIST was performed. The molecular examination indicated a KIT exon 11 deletion mutation in both the primary GIST and recurrent GIST. An additional point mutation was observed in the recurrent GIST in exon 17 that caused resistance to IM. The present case might indicate that extensive removal of the tumor cells through surgery and long-term administration of IM without an interruption or a dose change were important for achieving improved recurrence-free survival in patients with ruptured GISTs of the small intestine with peritoneal metastases.

Pancreatic acinar cell carcinoma with a ductal adenocarcinoma component: a case report and analysis of the histogenesis of the tumor.

BACKGROUND: Pancreatic cancer composed of acinar cell carcinoma (ACC) and ductal adenocarcinoma (DAC) is rare, and the clinicopathological characteristics of ACC with DAC have yet to be elucidated. Herein, we report a case of ACC with a DAC component of the pancreas and examined the histogenesis of this tumor. CASE PRESENTATION: A 69-year-old man was admitted to our hospital complaining of appetite loss, constipation, epigastric dull pain, and jaundice. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a pancreatic head tumor with dilatation of the bile duct and the distal main pancreatic duct. Under the diagnosis of pancreatic head cancer, a pancreatoduodenectomy was performed. The histology of the resected tumor consisted of mainly ACC with a focus of DAC, which was confirmed by mucin staining and immunohistochemistry for antigens such as BCL10, trypsin, Smad4, p16, p53, and MUC1. There was histological transition between the components of ACC and DAC, and immunostaining of the transitional zone showed equivocal results for the antigens. KRAS was wild-type in both ACC and DAC. The patient was treated with adjuvant chemotherapy with S-1 for 1 year. No evidence of recurrence or metastasis was observed after 9 years of follow-up. CONCLUSIONS: A rare case of pancreatic ACC with a DAC component in a patient with long-term survival after surgery was reported. Immunohistochemical and molecular analysis indicated that DAC might have arisen from ACC through transdifferentiation in this case.

Sarcomatoid carcinoma of the pancreas with rare long-term survival: a case report.

BACKGROUND: Sarcomatoid carcinoma of the pancreas (SCP) tends to have similar or even worse prognosis than that of conventional pancreatic ductal adenocarcinoma. The clinical and pathological features of SCP remain poorly characterized owing to its rarity. CASE PRESENTATION: A 58-year-old man was admitted to our hospital with the chief complaints of upper abdominal pain and weight loss. Abdominal contrast computed tomography revealed a 5-cm low-density mass in the pancreatic body. Magnetic resonance cholangiopancreatography revealed an obstruction of the main pancreatic duct and a dilation of the distal main pancreatic duct. Based on the clinicoradiological findings, pancreatic body cancer was suspected, and the distal pancreatectomy was performed. A pathological examination revealed that the tumor was composed of an area of invasive ductal adenocarcinoma and an area of sarcomatous spindle-shaped cells; the latter component predominated. The spindle cells were immunohistochemically positive for both cytokeratin and vimentin, and thus, a pathological diagnosis of SCP was made. In addition, immunohistochemical analysis suggested the sarcomatous component might be derived from the adenocarcinoma component via the process of epithelial-mesenchymal transition. After the operation, the patient received 6 months of chemotherapy with gemcitabine. At 10 years after the operation, the patient is alive with no recurrence. CONCLUSIONS: The current case study presented a SCP patient with long-term survival after the operation. It was worth noting that the sarcomatous component of the tumor pathologically showed lower MIB-1 labeling index compared with those in previously reported SCP cases, which might account for the long-term survival of the patient.

A Rare Case of Moderately Differentiated Adenocarcinoma With PD-L1 Overexpression and a Heterogeneous LELC Component in the Ascending Colon.

BACKGROUND: Lymphoepithelioma-like carcinomas (LELCs), especially colorectal cancers (CRCs), are uncommon pathological phenotypes generally associated with poor aggressiveness and a preferable prognosis. However, PD-L1 overexpression in CRCs is associated with poor outcomes. We report a case of moderately differentiated adenocarcinoma with PD-L1 overexpression, an LELC component, and Crohn's-like lymphoid reaction (CLR) presenting with extreme locoregional aggression and complete remission with chemotherapy after noncurative excision. CASE PRESENTATION: A 69-year-old man was referred to our hospital for abdominal fullness and pain. Computed tomography (CT) showed a circumferential tumor in the ascending colon, accompanied by bulky swollen lymph nodes. Under the preoperative diagnosis of T4N2M1 (lymph nodes) ascending colon cancer, we performed a right hemicolectomy; however, paracaval and parailiac vein lymph nodes were abandoned. Pathological findings showed moderate to poorly differentiated adenocarcinoma invading the subserosa accompanied by an LELC component invading the superficial muscularis propria. Lymph node metastases were found in a neighboring tumor and in retroperitoneal lymph nodes with glandular differentiation. No relation to microsatellite instability (MSI) or Epstein-Barr virus (EBV) was observed. In the component with glandular differentiation, PD-L1 overexpression was revealed. CLR findings were also observed. The tumor was diagnosed as T3N2M1 cancer that was moderately to poorly differentiated and had an LELC component. The patient was treated with chemotherapy, and the metastasized lymph nodes ultimately disappeared. He was alive without tumor recurrence 5-years post-operation. CONCLUSION: This is a very rare case of moderately differentiated adenocarcinoma with PD-L1 overexpression and a heterogeneous LELC component that developed in the ascending colon. Unlike the previously reported weak aggressive properties of LELCs, the present case showed an extremely aggressive locoregional extent, but complete remission was finally achieved with chemotherapy. This type of LELC with CLR could be associated with a good response to chemotherapy and a good prognosis in CRC patients.

Cystic lymphangioma in the peripheral jejunal mesentery in an adult and excision with laparoscopic-assisted surgery: a case report.

BACKGROUND: Lymphangiomas are uncommon congenital malformations that present mainly in the head, neck, and axillar regions in pediatric patients. Mesenteric cystic lymphangiomas (MCLs), which occasionally present with substantial growth and the invasion of adjacent vital structures, are rarely reported in adults. We report a case of MCL in an adult who was treated with laparoscopic-assisted excision. CASE PRESENTATION: A 40-year-old Japanese man visited his family physician for prolonged periumbilical pain. Plain computed tomography (CT) showed a low-density mass in his left abdomen, and he was referred to our hospital 2 weeks later. His abdomen was flat and soft, and no mass was felt upon palpation. Routine laboratory data showed no abnormalities in the blood cell counts. The levels of tumor markers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125), were within normal ranges. Contrast-enhanced CT was performed, and a low-density mass was observed with an irregular outline and poor contrast, as well as involvement of the peripheral mesenteric artery and partial compression of the adjacent jejunum without dilatation of the oral side of the bowel. The patient was diagnosed with lymphatic cysts and observed for 1 month without symptom exacerbation. Follow-up CT showed no increase in the size of the mass but showed apparent invasion of the jejunal wall without bowel obstruction. Magnetic resonance imaging (MRI) showed intermediate intensity on T1-weighted imaging (T1WI) and high intensity on T2-weighted imaging (T2WI). The coronal view on T2WI clearly showed an accumulation of cystic lesions. We performed tumor excision with partial resection of the jejunum in a laparoscopic-assisted manner. Pathological examination showed multicystic lesions with an attenuated endothelial lining, surrounding rich adipose tissue and scattered smooth muscle fibers; the patient was diagnosed with MCL. Immunohistochemical assays supported this diagnosis. CONCLUSIONS: This is rare case of MCL presenting in an adult who underwent successful laparoscopic-assisted resection. Mesenteric lymphangioma (ML) should be considered in the differential diagnosis of patients with intraabdominal cysts. Radical excision is optimal, even when the patient is asymptomatic. Laparoscopic-assisted tumor resection is a suitable surgical method for treating MLs located in the peripheral mesentery.

Double primary recurrent human epidermal growth factor receptor 2-positive breast cancer and esophageal cancer that responded well to chemotherapy.

Double primary breast and esophageal cancer have been no reported cases in which treatment methods other than surgery were selected because of multiple metastasis or advanced cancer. The patient was a 52-year-old woman who had received left pectoral muscle-preserving mastectomy and axillary lymph node dissection (level 2) 7 years prior, following the diagnosis of left breast cancer. The postoperative diagnosis was pT2 N3a M0 stage IIIC and luminal human epidermal growth factor receptor 2 (HER2) phenotype. After the surgery, six courses of triple chemotherapy with 5-fluorouracil (5-FU), epirubicin, and cyclophosphamide and four courses of docetaxel (DTX) were administered, and letrozole was administered for 5 years. Seven years after the surgery, swelling of her left axillary, supra-, and subclavicular lymph nodes, and sternum osteolysis were observed on computed tomography (CT). Radioisotope uptake was observed in the esophagus on positron emission tomography. An esophageal cancer was observed in the upper thoracic esophagus on esophagogastroscopy. The patient was administered a local treatment for esophageal cancer and systemic chemotherapy for both cancers. As a primary therapy, double chemotherapy with 5-FU and cisplatin (FP) (two courses) + radiotherapy on the esophagus and left supraclavicular lymph nodes (total target dose of radiotherapy was 60 Gy /30 fractions) was performed with the concomitant use of trastuzumab and zoledronate. Marked shrinkage [complete response (CR)] of the esophageal cancer was observed on esophagogastroscopy and shrinkage (partial response) of the left axillary and supra- and subclavicular lymph nodes were observed on CT. The secondary treatment included pertuzumab + trastuzumab + DTX. Bilateral pleural effusions were observed in the eighth course; therefore, DTX was withdrawn and the treatment was continued with only the molecularly targeted drugs. Two years have passed since the initiation of treatment. The individual lymph node metastatic foci have disappeared or markedly shrunk (CR) on CT scans and the sternal metastases have remained hard without change. In addition, CR for esophageal cancer has been maintained. We report a case of double primary recurrent HER2-positive breast cancer and esophageal cancer that responded well to radiotherapy and chemotherapy.

Effects of bafilomycin A1, a vacuolar type H+ ATPase inhibitor, on the thermosensitivity of a human pancreatic cancer cell line.

PURPOSE: It has been known that the thermosensitivity of tumour cells can be increased by lowering intra-cellular pH (pHi) by inhibiting pHi control mechanisms. The pHi is partially controlled by transport of H+ from cytoplasm into endocytic and secretary systems in the cells mediated by vacuolar type H+ATPase and also by transport of H+ through plasma membrane. METHODS: This study investigated the effects the bafilomycine A1, an inhibitor of the vacuolar type H+ATPase and the EIPA, an inhibitor of the Na+/H+ exchanger in plasma membrane, on thermosensitivity of AsPC-1 cells, a human pancreatic cancer cell line. It also investigated the effects of combination of bafilomycine A1 and EIPA. RESULTS: The treatment of cancer cells with bafilomycine A1 or EIPA individually slightly lowered pHi of the cells in vitro and increased the thermosensitivity of the cells. CONCLUSION: The combination of these two drugs significantly lowered pHi and increased thermosensitivity of cancer cells in vitro and enhanced the heat-induced the growth delay of AsPC-1 tumours grown s.c in the legs of BALB/cA nude mice.