[A Case of Primary Gastric Lymphoma with Spontaneous Perforation].

An 85-year-old female patient presented to the emergency department with the chief complaint of sudden upper abdominal pain. The patient suffered from anorexia and epigastric pain for a month, and a local physician suspected a diagnosis of gastric ulcer. An abdominal computed tomography(CT)scan showed intraperitoneal free air as well as irregular thickening and thinning of the gastric wall. Gastric ulcer perforation was suspected, and an emergency operation was performed. Surgical findings showed thickening of the gastric wall in the pylorus and gastric corpus but partial thinning of areas of the anterior wall of the gastric corpus with a perforation measuring 5 mm. A distal gastrectomy and reconstruction were performed using the Billroth Ⅱ method. The histopathological diagnosis was malignant gastric lymphoma(diffuse large B- cell lymphoma). Considering the patient's age and general condition, chemotherapy was not administered after surgery. The patient was alive without recurrence 8 months after the operation.

[Resectable Pancreatic Cancer Successfully Treated with Neoadjuvant Chemotherapy Regimen Change to Modified FOLFIRINOX-A Case Report].

A 72-year-old woman presented with obstructive jaundice. Computed tomography revealed a 12-mm low-density mass in the head of the pancreas. She was diagnosed as having pancreatic cancer by endoscopic ultrasound-guided fine-needle aspiration. She received gemcitabine plus nab-paclitaxel as preoperative chemotherapy. After 2 courses, hepatoduodenal lymph node metastasis appeared and was accompanied by increased tumor marker levels. The regimen was changed to modified FOLFIRINOX. After 5 courses, the lymph node metastasis was reduced in size and the tumor marker levels were decreased, so subtotal stomach-preserving pancreaticoduodenectomy was performed. Adjuvant chemotherapy was administered postoperatively. The patient was alive and well without recurrence 2 years and 9 months after the surgery, but died of sepsis. Nevertheless, this case highlights that when preoperative chemotherapy for resectable pancreatic cancer appears to be ineffective, a change in regimen may be useful.

[A Case of Pancreatic Invasive Micropapillary Carcinoma That Survived Seven Years after Resection and Chemotherapy].

We present the case of a 47-year-old man who underwent a subtotal stomach-preserving pancreaticoduodenectomy for pancreatic head cancer. Histopathological diagnosis revealed that the majority of the cancer was an invasive micropapillary carcinoma(IMPC). Postoperative adjuvant chemotherapy using S-1 was continued for 4 years, at the end of which, multiple lymph node metastases were identified. Therefore, gemcitabine plus S-1 therapy was initiated. The treatment reduced the lymph node in size and resulted in the maintenance of a partial response for a year and a half. However, increased lymph node metastases recurred, and multiple lung metastases were noted. The patient died 7 years and 2 months after the resection of the primary lesion. Although pancreatic IMPC has a poor prognosis, long-term survival may be achieved by resection of the primary region, the administration of adjuvant chemotherapy and management of recurrent lesions by chemotherapy.

[Total Pancreatectomy for Remnant Pancreatic Cancer with Positive Washing Cytology after Conversion to Negative Cytology Following Gemcitabine plus Nab-Paclitaxel Therapy-A Case Report].

A 53-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)for resectable pancreatic cancer after neoadjuvant chemotherapy. Postoperatively, she received hepatic arterial infusion of 5-FU and S-1 chemotherapy. Two years after SSPPD, abdominal computed tomography showed a 2-cm mass in the remnant pancreas, which was diagnosed as recurrence of cancer by endoscopic ultrasound-guided fine-needle aspiration. Staging laparoscopy was performed and peritoneal washing cytology(CY)was positive. She then received gemcitabine plus nab-paclitaxel chemotherapy for 8 months. After that, staging laparoscopy was performed again and negative CY was confirmed. A total remnant pancreatectomy with splenectomy was performed. She received chemotherapy after pancreatectomy and is now alive and well without recurrence 2 years and 1 month after the second surgery. Although positive CY is a poor prognostic factor, surgery combined with perioperative chemotherapy may contribute to prolonged survival for some patients who have recurrence in the remnant pancreas with positive CY.

[A Case of Surgical Resection of Anaplastic Carcinoma of the Pancreas(Pleomorphic Cell Type)with Poor Response to Neoadjuvant Chemotherapy].

A 62-year-old man was incidentally found to have a pancreatic tumor by CT. He was diagnosed with pancreatic cancer by EUS-FNAB. Gemcitabine(GEM)plus nab-paclitaxel(PTX)was started as neoadjuvant chemotherapy(NAC)for resectable pancreatic cancer. However, after the end of the second course, the tumor grew rapidly and invaded the stomach, so NAC was discontinued, and surgery was performed. The pathological diagnosis was anaplastic ductal carcinoma of the pleomorphic cell type, and the histological response was Grade 1a. Multiple liver metastases appeared during adjuvant chemotherapy with S-1, so GEM plus nab-PTX and modified FOLFIRINOX were administered, but the therapeutic response was poor, the patient died 9 months after surgery. Anaplastic carcinoma has a poor response to chemotherapy and may be included with cancers showing treatment resistance to NAC, as seen in our case. It is necessary to pay attention to anaplastic carcinoma during the course of NAC for pancreatic cancer.

Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry.

Although several reports have highlighted neoplastic PD-L1 (nPD-L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV-CHL), with and without Epstein-Barr virus (EBV) association, and highlight the diagnostic utility of PD-L1 (clone SP142) immunohistochemistry. The patients were a 61-year-old male, 45-year-old male, 85-year-old female, and 89-year-old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV-CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed-Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD-L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD-L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing 'confluent' sheets in the diagnostic workup for SV-CHL.

[A case of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in an elderly woman].

An 84-year-old woman who had diabetes mellitus and atrial fibrillation presented to our hospital with appetite loss and difficulty in standing up. Her cervical, axillary, and mediastinal lymph nodes were swollen. At first, malignant lymphoma was suspected, but positron emission tomography-computed tomography and cervical lymph node biopsy did not support this diagnosis. She was admitted to our hospital 41 days after the first consultation because of appetite loss and fever. We suspected a disorder related to Epstein-Barr virus infection because Epstein-Barr virus-encoded small RNAs were found in the lymph node. She was diagnosed with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) based on the diagnostic criteria of the Japanese Society for Pediatric Infectious Diseases. Her symptoms, including appetite loss and fever, were alleviated after the administration of prednisolone (20 mg per day). She was discharged 90 days after admission. At two weeks after discharge, she was readmitted for respiratory failure, and died five days after readmission.To the best of our knowledge there are no previous reports of EBV-HLH in patients over 80 years of age, and the optimal treatment strategy is unknown. This case suggested that prednisolone may alleviate the symptoms of EBV-HLH. When a patient presents with swollen lymph nodes, clinicians should keep the possibility of EBV-HLH in mind.

Sauvé-Kapandji procedure with headless compression screw in patients with rheumatoid arthritis.

OBJECTIVE: We examined the surgical outcomes of the Sauvé-Kapandji (S-K) procedure using a headless compression screw and a metal cancellous screw in patients with rheumatoid arthritis (RA). METHODS: This retrospective study included 41 RA patients who underwent the S-K procedure for distal radioulnar joint disorders with two screws: headless compression screws (HCS group, n = 20) and cannulated cancellous screws (CCS group, n = 21). Clinical and radiographic outcomes were assessed 1 year after surgery. Radiographic outcomes included bony union of the distal radioulnar joint (DRUJ), bone resorption around the screw, a screw back-out, and use of additional K-wire. We investigated any complications related to the screw head. RESULTS: All 20 patients in the HCS group showed bone fusion of the DRUJ. In the CCS group, an asymptomatic non-union was observed in one patient and additional K-wire was needed to stabilize the DRUJ in three patients. No patients complained of any complications related to the screw head in the HCS group, while the CCS group demonstrated the hardware protrusion in two patients who complained of tenderness or discomfort at the screw head. CONCLUSIONS: The use of a headless compression screw in the S-K procedure is useful in patients with RA.

Disuse Atrophy Accompanied by Intramuscular Ectopic Adipogenesis in Vastus Medialis Muscle of Advanced Osteoarthritis Patients.

Muscle dysfunction is the most important modifiable mediating factor in primary osteoarthritis (OA) because properly contracting muscles are a key absorber of forces acting on a joint. However, the pathological features of disuse muscle atrophy in OA patients have been rarely studied. Vastus medialis muscles of 14 female patients with OA (age range, 69 to 86 years), largely immobile for 1 or more years, were obtained during arthroplastic surgery and analyzed histologically. These were compared with female patients without arthritis, two with patellar fracture and two with patellar subluxation. Areas occupied by myofibers and adipose tissue were quantified. Large numbers of myofibers were lost in the vastus medialis of OA patients. The loss of myofibers was a possible cause of the reduction in muscle strength of the operated on knee. These changes were significantly correlated with an increase in intramuscular ectopic adipose tissue, and not observed in knees of nonarthritic patients. Resident platelet-derived growth factor receptor α-positive mesenchymal progenitor cells contributed to ectopic adipogenesis in vastus medialis muscles of OA patients. The present study suggests that significant loss of myofibers and ectopic adipogenesis in vastus medialis muscles are common pathological features of advanced knee OA patients with long-term loss of mobility. These changes may be related to the loss of joint function in patients with knee OA.

Sclerosing adenosis as a predictor of breast cancer bilaterality and multicentricity.

Breast cancer is occasionally complicated by sclerosing adenosis (SA). Although both lesions usually originate in the terminal duct lobular unit, their pathogenetic relationship has not yet been elucidated. The present study analyzed 63 breast cancer patients with SA (involving a total of 75 breasts) to clarify if coexisting SA increased the frequency of multicentric breast cancer or not. Using the topographical classification proposed in our previous study, breast cancers with SA were classified into the following three types: type A (n = 22), cancer area was completely surrounded by the SA; type B (n = 26), cancer area partially overlapped the SA; and type C (n = 27), cancer area was located separate from the SA. Breast cancers with SA had a significant (P < 0.001) increase in frequency of harboring bilateral and multicentric cancers [17 of 63 (27%) and 15 of 63 (24%), respectively] when compared to breast cancer patients without SA, regardless of topographical type. Breast cancers with SA were less invasive (P < 0.001), of lower histological grade (P = 0.034), and had similar frequency of estrogen receptor-positive (P = 0.21) and HER2-positive (P = 0.74) tumors. In conclusion, contralateral and ipsilateral multicentric breast cancers occurred at a higher frequency in those with SA. Our data suggest that SA is, in addition to lobular neoplasia, a predictor of multicentric breast cancers.

[A Case of Long-Term Survival of a Patient with Liver Metastasis of Colon Cancer and Suspected Inferior Vena Cava Invasion].

A 58-year-old woman was diagnosed with a sigmoid colon cancer and synchronous liver metastasis. Because an obstruction of the sigmoid colon was identified, the patient underwent sigmoidectomy. Computed tomography(CT)findings suggested possible vena cava and hepatic vein invasion. Therefore, the decision was made to offer systemic chemotherapy. The patient underwent 6 courses of chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6). After 4 courses of chemotherapy, CT scans showed a significant reduction of the liver metastasis (reduction rate of 5 0%; a partial response) and demonstrated improved exclusion of the inferior vena cava and hepatic vein. After 6 courses of chemotherapy, we performed right trisegmentectomy of the liver and resection of the inferior vena cava and diaphragm. Postoperative pathological findings revealed negative margins, and no invasion of the inferior vena cava. The pathological response grade of the tumor after chemotherapy was determined to be Grade 2. Adjuvant chemotherapy was not performed because of the patient 's poor performance status. The patient was alive with no recurrence 8 years after resection of the liver metastasis.

Immunohistochemical expression of myoepithelial markers in adenomyoepithelioma of the breast: a unique paradoxical staining pattern of high-molecular weight cytokeratins.

To determine which immunohistochemical markers are useful for the identification of neoplastic myoepithelial cells in adenomyoepithelioma of the breast, the expression of seven myoepithelial markers (α-smooth muscle actin (α-SMA), calponin, p63, CD10, cytokeratin 5/6, cytokeratin 14, and S-100) was examined in 19 lesions from 16 patients. The lesion consisted of seven spindle and 12 clear cell lesions. For normal myoepithelial cells, α-SMA, calponin, and p63 were significantly more sensitive than cytokeratin 5/6, cytokeratin 14, and S-100. There was no significant difference in the expression of α-SMA, calponin, p63, and CD10 in neoplastic myoepithelial cells of adenomyoepithelioma regardless of spindle or clear cell types. In spindle cell lesions, high-molecular weight cytokeratins (HMWCK; cytokeratin 5/6 and cytokeratin 14) tended to show higher staining scores and S-100 showed lower staining scores than other markers. In clear cell lesions, HMWCK showed significantly lower staining scores than the other five markers. There was no significant difference in staining scores among the other five markers. HMWCK showed a unique paradoxical staining pattern in clear cell lesions, with diffusely positive inner epithelial cells and completely negative outer myoepithelial cells. Although the sensitivity of HMWCK in clear cell lesions is low, with this unique paradoxical staining pattern and relatively high sensitivity in spindle cell lesions, HMWCK could be useful in diagnosing adenomyoepithelioma. In choosing immunohistochemical markers, any of the seven markers are useful, but combining HMWCK and any one of α-SMA, calponin, and p63 would be a good panel for the diagnosis of adenomyoepithelioma.

Uniqueness of ductal carcinoma in situ of the breast concurrent with papilloma: implications from a detailed topographical and histopathological study of 50 cases treated by mastectomy and wide local excision.

AIMS: To clarify the diagnostic clues of ductal carcinomas in situ (DCIS) associated with papilloma and optimal clinical management of papilloma diagnosed on core needle biopsy (CNB). METHODS AND RESULTS: A total of 50 surgically resected cases were examined histopathologically and topographically. Thirty-nine cases (78%) spread in segmental fashion. Papilloma and DCIS were intermingled closely in 44 cases (88%), occupying the same areas in varying proportions from DCIS-predominant to papilloma-predominant. The two components occupied discrete areas and collided focally in six cases (12%). Most were non-high-grade. Cribriform and solid architectures with fibrovascular stroma were frequent. The cribriform pattern was unique, consisting of fused tubules separated by fibrovascular stroma. Intraductal myoepithelial cells were present to varying degrees in 40 cases (80%). In 38 cases (76%), points were identified where papilloma and DCIS coexisted or collided within a single lumen (CC point). Forty-eight cases (96%) had either intraductal myoepithelial cells or CC points, implying that DCIS and papilloma existed in the same duct system. Radiology showed segmental abnormalities in 83% of the available cases. CONCLUSIONS: Intraductal myoepithelial cells do not always guarantee benignity. Surgical resection is recommended for papilloma in CNB when radiology shows segmental abnormalities.

Ductal carcinoma in situ with isolated tumor cells in the sentinel lymph node in a 17-year-old adolescent girl.

We report here a quite rare case of ductal carcinoma in situ (DCIS) with isolated tumor cells in the sentinel lymph node in a 17-year-old adolescent girl whose mother also had advanced breast cancer. Findings included an elastic mass in the right breast accompanied by serous nipple discharge. DCIS of the breast was diagnosed following core needle biopsy. Although no invasive focus was clearly observed in the mastectomy sample, isolated tumor cells were found in the sentinel lymph node. Although the family refused genetic testing, a hereditary abnormality may have played a role in the carcinogenesis in this case.

Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia.

Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.

Intracytoplasmic lipid accumulation in apocrine carcinoma of the breast evaluated with adipophilin immunoreactivity: a possible link between apocrine carcinoma and lipid-rich carcinoma.

Although apocrine carcinoma is a distinct histologic entity, there is no immunohistochemical marker to confirm apocrine differentiation with high sensitivity and specificity, and its differential cytologic characteristics are still not fully clarified. Despite the foamy cytoplasm of some apocrine carcinomas and the existence of lipid in the normal apocrine gland, intracytoplasmic lipid in apocrine carcinomas has not been fully explored. By using immunohistochemistry for adipophilin, which is a specific marker of lipid accumulation that can be applied to paraffin sections, we examined intracytoplasmic lipid in apocrine carcinomas. Twenty-four of 26 (92%) apocrine carcinomas and 38 of 116 (33%) nonapocrine carcinomas contained intracytoplasmic lipid. The frequency of adipophilin-positive cases was significantly higher in apocrine carcinomas compared with nonapocrine carcinomas (P<0.01). The positive cell rate per tumor ranged from 10% to 70% (mean, 29%) for apocrine carcinomas. The staining density was heterogeneous from cell to cell. There was no difference in the staining pattern of adipophilin between apocrine ductal carcinoma in situ and invasive apocrine carcinoma or between eosinophilic cells and foamy cells. Sporadic or mosaic distribution of adipophilin-positive cells throughout the tumor and microvesicular or fine granular cytoplasmic staining with heterogeneous density were characteristic features of apocrine carcinoma. Although intracytoplasmic lipid was identified in most apocrine carcinomas, none of the apocrine carcinomas contained prominent intracytoplasmic lipid in >90% of the tumor cells; thus, the criteria for lipid-rich carcinoma was not fulfilled. However, the immunohistochemical study suggests that lipid-rich carcinomas are closely related to apocrine carcinomas.

Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ.

AIM: To examine the histopathological features of 24 surgically resected carcinoma in situ (CIS) involving sclerosing adenosis (SA), with special reference to the topographical relationship between CIS and SA. METHODS AND RESULTS: In 13 (54%) lesions, CIS was entirely surrounded by SA (type A) and in 11 (46%), CIS involved SA at least focally but was not confined to the SA area (type B). The mean size of CIS in type B (30.45 mm) was significantly larger than in type A (18.00 mm). The mean size of SA in type A (39.46 mm) was significantly larger than in type B (19.54 mm). Most type A CIS were non-high-grade, and the oestrogen receptor (ER)(+)/progesterone receptor (PgR)(+)/HER2(-) immunophenotype predominated. Most type B CIS were high-grade and six (54%) were ER(-)/PgR(-). Most type A were bcl-2(+)/p53(-) in both SA and CIS areas, but two (18%) apocrine ductal CIS of type B were bcl-2(-)/p53(+) in both SA and CIS areas. Expression of ER and cyclin D1 in SA was not different from that of SA unassociated with cancer. CONCLUSIONS: Most CIS involving SA arises within SA and high-grade DCIS tends to grow beyond SA. Occasional CIS may arise outside SA and secondarily involve SA.

Dedifferentiation and progression of an intracranial solitary fibrous tumor: autopsy case of a Japanese woman with a history of radiation therapy of the head during infancy.

Solitary fibrous tumor (SFT) is usually an indolent neoplasm with a low rate of local recurrence and metastasis. Although dedifferentiation of low-grade sarcoma is well documented, the concept of dedifferentiated SFT was not recognized until recently. A case of intracranial SFT with seven recurrences within 5 years, showing progression and dedifferentiation during the course of disease, is reported here. A 51-year-old woman with a history of irradiation during infancy presented with a SFT in the right posterior fossa. Because of the close proximity to the brain stem, the tumor could not be removed completely. The tumor recurred 12, 16, and 28 months after the initial operation. With the repeated recurrences, cellularity, mitotic count, and Ki-67 (MIB-1) index increased gradually. The histology suddenly changed at the fourth recurrence, which occurred 16 months after postoperative radiation therapy for the third recurrence. The tumor revealed a fibrosarcoma-like appearance with necrosis and markedly increased mitotic activity. The tumor further recurred 50, 52, and 55 months after the initial operation with the same fibrosarcoma-like histology. The patient died of uncontrolled tumor 58 months after the initial operation. In this case radiation may have played some role in the tumorigenesis, progression, and dedifferentiation of the SFT.

Measurement of human epidermal growth factor receptor type-2 extracellular domain and cancer antigen 15-3 levels in needle washout fluid: a potential adjunct to the cytological diagnosis of breast cancer.

To determine whether the measurement of biomarkers in the needle washout fluid after fine needle aspiration cytology could strengthen cytological diagnosis, 29 benign lesions, 26 ductal carcinomas in situ (DCIS), and 95 invasive carcinomas of the breast were analyzed. Immediately after the aspiration samples were expelled onto glass slides, the needle was rinsed out with 2 ml of saline. Human epidermal growth factor receptor two extracellular domain (HER2-ECD) and cancer antigen 15-3 (CA 15-3) in the washout fluid were measured using chemiluminescence. The measuring limit for HER2-ECD (0.5 ng/ml) and that for CA 15-3 (4 U/ml) were used as the cutoff values, respectively. The proportion of patients with positive HER2-ECD values was 6.9% in cases of benign lesions, 26.9% in DCIS, and 10.5% in invasive carcinomas. The proportion of patients with positive CA 15-3 values was 6.9% in cases of benign lesions, 42.3% in DCIS, and 10.5% in invasive carcinomas. The proportion of patients with any biomarker elevation was 6.9% in cases of benign lesions, 46.2% in DCIS, and 15.8% in invasive carcinomas. Thus, biomarker elevation was most frequent in cases of DCIS, followed by invasive carcinomas (P < 0.01). HER2-ECD values over 6 ng/ml or CA 15-3 values over 25 U/ml were seen exclusively in cases of DCIS or invasive ductal carcinomas with an extensive intraductal component. If the biomarker status is included, 5 of 12 cases of DCIS with equivocal cytology categories would be upgraded. Further clinicopathological validation is necessary before applying this new approach to the clinical setting.