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A 63-year-old woman presented with a fever, eruption, and sterile pyuria. A cystoscopic examination revealed submucosal nodular lesions in the trigone of the bladder, and a biopsy specimen showed epithelioid cell granulomas in the lamina propria of the bladder. Mycobacterium avium grew in the urine culture. Other organ involvement, such as the lungs, spleen, bones, muscles, and pelvic lymph nodes, was observed on radiological examinations, and M. avium was isolated from some organ lesions. Interferon-γ-neutralizing autoantibodies were detected in the patient's serum. Therefore, the patient was diagnosed with disseminated M. avium infection, which was resolved with antimycobacterial treatment.

A 48-year-old man was admitted due to marked leukocytosis. Bone marrow examinations resulted in a diagnosis of Philadelphia (Ph) chromosome-positive chronic myeloid leukemia. One month later, massive muscle and bone invasion by leukemic cells was detected. After induction chemotherapy, he complained of a headache and visual loss, which was caused by a leukemic infiltration in the central nervous system. After temporary remission in response to chemotherapy, the disease relapsed in the form of an intracranial tumor. The unusual t(14;22)(q24;q11.2) translocation of the Ph-chromosome and the significant increase in monocytes observed might have contributed to the unique and aggressive clinical course.

A 77-year-old man was suspected of having tumor-induced osteomalacia (TIO) because of hypophosphatemia (1.9 mg/dL) and elevated serum fibroblast growth factor 23 (FGF23) level (186.9 pg/mL). We detected a tumor in his left parotid gland, and the FGF23 level in the left external jugular vein indicated that the tumor overproduced FGF23. After the removal of the tumor, the serum FGF23 level rapidly decreased, and the serum phosphate normalized. This is the first case of TIO caused by a tumor in a parotid gland. This case indicates that the responsible tumors for TIO can be quite diverse.

Morphologically, an inflammatory fibroid polyp (IFP) is usually centred in the submucosa. Extension of an IFP to the subserosa with destruction of the muscularis propria is exceedingly rare. Herein, we describe a 70-year-old woman who presented with right lower abdominal pain but was finally diagnosed with an IFP. Contrast-enhanced computed tomography revealed a target-like structure with a hypovascular mass at the leading edge, which was consistent with intussusception due to a tumour. Following surgery, the resected specimen displayed a mass measuring 4 × 3 × 3 cm that was protruding into the lumen. Microscopically, the mass was centred in the submucosa, extending up to the mucosal surface and down to the subserosa and serosa. The muscularis mucosae and muscularis propria were destroyed focally. A PDGFRA gene mutation in exon 2 (1837_1851 del) that was found in this case, as well as a highly infiltrative growth pattern, strongly supported the neoplastic nature of IFP.

Cytological features of gastrointestinal stromal tumors (GISTs) have been reported, especially regarding fine-needle aspiration cytology, including immunostaining for c-kit and DOG1. Meanwhile, cytological findings of GISTs on ascites cytology have rarely been reported, which may be owing to the rare appearance of GIST tumor cells in ascites. Herein, we present a 66-year-old woman who had disseminated GISTs in the abdomen. The GIST tumor cells appeared sparsely in the ascites smear cytology using ascites obtained at the time of autopsy. Even when widespread intra-abdominal dissemination takes place, GISTs may be hard to detect in ascites smear cytology, based on the experience of this case. However, immunohistochemistry of DOG1 using a cell block preparation was found to clearly visualize the GIST tumor cells, although they were sparsely present. Immunostaining of c-kit did not provide as clear an identification of the tumor cells as DOG1 did. When suspicious about GISTs, it is wise to prepare a cell block to make it possible to visualize the tumor cells immunohistochemically.

Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstein-Barr virus (EBV) sometimes contributes to the development of MTX-associated LPD. Herein, we report the case of a 64-year-old Japanese woman with RA who showed complications of EBV-positive MTX-associated LPD. This case is exceedingly rare in that the LPD was confined to the lungs and its subclassification was extranodal NK/T-cell lymphoma. Only four cases of extranodal NK/T-cell lymphoma in the setting of MTX-associated LPD have ever been reported in the English language literature, only one of which was an extranasal NK/T-cell lymphoma, similar to our case. Extranasal NK/T-cell lymphomas show more aggressive behavior than nasal NK/T-cell lymphomas, possibly reflected by the considerable re-exacerbation of the lesions in only two months after the cessation of MTX in our case. However, the SMILE regimen (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) was able to suppress tumor growth in this case.

Perivascular epithelioid cell tumors (PEComas) most frequently involve the uterus, particularly the uterine corpus and very occasionally the cervix. One case of PEComa identified using a conventional cervical smear has previously been documented. Herein, we present the second such case. The patient was a 51-year-old woman with abnormal genital tract bleeding. Samples collected for conventional cervical smears were submitted for cytopathological examination, which revealed discohesive monotonous tumor cells showing epithelioid morphology, ample cytoplasm that was pale to weakly eosinophilic, and mildly enlarged nuclei. The cytopathological features were well correlated with histopathological findings. Upon immunohistochemistry, the tumor cells were positive for both melanocytic and smooth muscle markers. Based on these findings, PEComa was diagnosed. Subsequently, a total hysterectomy with bilateral salpingo-oophorectomy was performed, revealing that the tumor (28 × 22 × 12 mm) was located at the superficial part of the endocervix. We propose that the cytopathological findings described herein can guide the diagnosis of PEComa, even though this tumor is rare.

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is rare compared with intraductal papillary mucinous neoplasm (IPMN). These entities are distinguished by endoscopic ultrasonography (EUS)-fine-needle aspiration cytology (FNAC) on the basis of mucin production and the presence of a tubular or papillary growth pattern. In addition, there are several tumor types that should be distinguished from ITPN, such as solid pseudopapillary neoplasm, acinar cell carcinoma, and pancreatic neuroendocrine tumor. Herein, a case of an 80-year-old man with ITPN, which was suspected based on EUS-FNAC findings at the time of review and confirmed by histological examination of the surgically resected specimen, has been presented. There have only been three reported cases that included the cytology of ITPN in the English language literature, all of which propose diagnostic features of ITPN based on cytological specimens. Here, a previously undescribed diagnostic feature of ITPN revealed by EUS-FNAC--tubules in contact with fibrovascular structures--correlated well with the histological findings of the surgically resected specimen, has been shown.

Intracranial germinomas comprise 0.5-2.0 % of all central nervous system (CNS) tumors and 50-60 % of CNS germ cell tumors. They most frequently originate in the pineal gland and the suprasellar region. The corpus callosum is an extremely uncommon location for germinoma formation. Herein, we report about a 20-year-old man with a germinoma centered at the corpus callosum and that extended to both cerebral hemispheres. In addition to its location, this case is unique in that the amount of tumor cells with rhabdoid morphology exceeded that of tumor cells with typical morphology. The rhabdoid cell component showed an immunophenotype compatible with germinoma. While the presence of rhabdoid cells is generally regarded as a sign of aggressive behavior, the patient has been doing well for at least 4 years since undergoing radiation therapy and chemotherapy. The cellular composition of germinoma might not critically affect prognosis with adequate treatment.

Intimal sarcoma (IS) is the most common sarcoma of the aorta. The platelet-derived growth factor receptor α (PDGFRA), murine double minute 2 (MDM2), and cyclin-dependent kinase 4 (CDK4) genes are often simultaneously amplified in IS. While immunohistochemical analysis of IS tissue has demonstrated frequent overexpression of the MDM2 and CDK4 proteins, the expression pattern of PDGFRA has not been well characterized, particularly in terms of intratumoral heterogeneity. Here, we present the case of a 46-year-old man who presented with a backache and was subsequently diagnosed with IS. Intratumoral heterogeneity of PDGFRA gene amplification was observed using fluorescence in situ hybridization and was positively correlated with PDGFRA protein expression using immunohistochemistry (IHC). The expression of PDGFRA was also correlated with cytological atypia: PDGFRA was not overexpressed in intimal spreading cells that displayed the lowest degree of atypia while PDGFRA overexpression and amplification were observed in invasive cells of progressive areas such as the aortic wall and a pulmonary metastatic site, which showed increased cytological atypia. Although PDGFRA has not been well examined on IHC, IHC of PDGFRA could be useful to diagnose IS. However, the areas within the tumor from which specimens are derived are important given potential intratumoral heterogeneity.

Paratesticular sarcoma is rare, but liposarcoma is its most common type. Paratesticular liposarcoma sometimes presents as dedifferentiated liposarcoma. Both high-grade and low-grade dedifferentiation have been reported. Herein, we presented a unique case of a 64-year-old man with low-grade dedifferentiated liposarcoma with prominent myxoid stroma. Well-differentiated liposarcoma components extended along the spermatic cord. The constituent cells of the dedifferentiated component were peculiar in that, they were relatively uniform cells with atypia and did not have pleomorphism to such an extent that it mimicked myxofibrosarcoma. This myxoid component was confidently differentiated from myxoid liposarcoma with the help of immunohistochemical analysis using CDK4 and MDM2. These two markers were also expressed in the well-differentiated component. It could therefore be confirmed that this sarcoma is dedifferentiated liposarcoma but is not mixed-type liposarcoma comprising well-differentiated liposarcoma and myxoid liposarcoma.

Lipid metabolic changes under diseased conditions, particularly in solid tumors, are attracting increased attention. However, in non-solid tumors, including most hematopoietic tumors, lipid analyses are scarce. Multiple myeloma (MM) is a plasma cell disorder arising from bone marrow, and the lipid status of MM cells has not been reported yet. In this study, we analyzed flow cytometry-sorted single MM cells and normal plasma cells (NPCs) using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), a two-dimensional label-free mass spectrometry technique for biomolecular analysis, to obtain specific lipid information. We isolated 1.31-5.77% of MM cells and 0.03-0.24% of NPCs using fluorescence-activated cell sorting (FACS). Analysis of purified cells using MALDI-IMS at the single-cell level revealed that the peak intensity and ion signals of phosphatidylcholine [PC (16:0/20:4) + H](+) at m/z 782.5 were significantly decreased in MM cells compared to NPCs. By examining particular cell populations rather than cell mixtures, our method can become a suitable tool for the analysis of rare cell populations at the single-cell level and advance the understanding of MM progression.

Primary salivary gland-type tumors of the lung are rare; among them, epithelial-myoepithelial carcinomas (EMC) represent a minor histological subtype. The present case documents an EMC that occluded the B8 segment of the left lung in a 72-year-old woman. Macroscopically, the tumor was well-demarcated; however, microscopic examination demonstrated that it had infiltrated the lung parenchyma. The majority of the tumor mass was composed of a myoepithelial overgrowth in conjunction with conventional bilayered ductal structures comprising epithelial and myoepithelial cells. At the advancing edge of the tumor, the myoepithelial overgrowth was observed to be gradually transitioning to a higher-grade component, which demonstrated venous invasion. The Ki-67 labeling index was reduced compared with high-grade transformation (HGT) of salivary gland EMC; p53 was sparsely observed on immunostaining. However, cyclin D1, which is reported to be overexpressed in certain subtypes of salivary gland carcinomas with HGT, was overexpressed in the higher-grade component of the tumor, indicating a potential HGT initiation. The surgical margin was tumor free, and no recurrence has been observed for 4 months. A thorough follow-up is required considering the HGT-like changes and venous invasion of the tumor. Additional studies are required to elucidate the characteristics of pulmonary EMC, with an emphasis on detecting HGT or HGT-like changes.

Breast carcinomas that produce chondroid matrix are extremely rare. If the carcinoma is invasive, it is classified as a matrix-producing carcinoma (MPC). Herein, we present a case of a breast carcinoma, which showed duct-replacing growth with chondroid matrix production. A 63-year-old woman underwent fine needle aspiration cytology for suspected malignancy, based on radiological findings. Cellular components showed sufficient atypia to allow a diagnosis of malignancy. A partial mastectomy was performed, and no mass-forming lesion was apparent in the surgically resected specimen. Histopathological examination showed that the carcinoma produced chondroid matrix and grew replacing ducts, which were associated with a small amount of an obvious invasive component without matrix production. Some parts of the duct-replacing component might take the form of expansile invasion due to the absence of residual duct-lining myoepithelial cells; it is difficult to decide whether the duct-replacing component is invasive or not. However, regarding a few tumor nests, they would be recognized as MPC-like intraductal components because of the focal presence of myoepithelial cells around them. Hence, this carcinoma could not be definitely diagnosed as a MPC, even though we believe they are closely related. This is the first reported case of a breast carcinoma displaying duct-replacing growth with chondroid matrix production.

Cord capillary hemangioma (CCH) of the spleen is an extremely rare lesion. Once classified under splenic hamartoma, CCH is now differentiated from hamartoma, as its clonality has recently been proven. Herein, we present the case of an incidentally found CCH, measuring 6 × 5.5 × 5 cm, in a 45-year-old man. He underwent splenectomy and has been recurrence-free for 8 years. Macroscopically, the cut surface of the mass showed a central stellate scar with peripheral interspersed reddish areas of variable sizes and intervening fibrous bands. Microscopically, the mass was well demarcated from the splenic tissue. The macroscopic reddish areas were found to correspond to nodules of various sizes, which were predominantly composed of CD34-expressing capillaries without the presence of CD8-expressing sinuses. The relative proportion of these two types of vessels distinguishes CCH from sclerosing angiomatoid nodular transformation (SANT), as SANT shows the apparent presence of CD8-expressing sinuses. In longstanding cases of SANT, sinuses might become ambiguous and the differences between CCH and SANT might become subtle. Nonetheless, immunohistochemistry should be performed when these conditions are suspected, since accurate distinction is usually achieved as a result.

Invasive urothelial carcinoma with chordoid features has not been reported since being first documented in 2009. Here we report a further case of it, involving an 85-year-old man with a papillary tumor of the urinary bladder, measuring 3 cm in diameter. This case is unique in that an epithelial-mesenchymal transition was suspected to have occurred in the transformation of a conventional urothelial carcinoma to a sarcomatoid variant, with invasive urothelial carcinoma with chordoid features acting as an intermediate stage. Based on this finding, we recommend that the presence of invasive urothelial carcinoma with chordoid features should be reported as it may predict the coexistence or future development of an aggressive sarcomatoid variant.

E-cadherin expression patterns in acinar cell carcinomas (ACCs) of the pancreas have not been well documented. Herein, we present a hitherto undescribed case of E-cadherin-negative ACC with a solid pseudopapillary growth pattern in a 65-year-old man. We used an antibody against the extracellular domain of E-cadherin. As a further unusual status in ACC, faint β-catenin expression was observed in the cytoplasm of carcinoma cells. Morphological distinction from a solid pseudopapillary neoplasm (SPN) of the pancreas might be problematic in such a case, because of their similarities concerned with the growth pattern and E-cadherin negativity. Without nuclear accumulation of β-catenin, a diagnosis of SPN was almost excluded. Immunoreactivity for trypsin and BCL10 made an accurate diagnosis of ACC to this case. The tumor recurred 10 months post-surgery as rapidly enlarging masses in the liver, presumably indicating the aggressiveness of the E-cadherin-negative phenotype among ACCs.

Here we present a patient with rheumatoid arthritis (RA), who was suspected to have developed malignant lymphoma during immunosuppressive therapy 5 years earlier. She temporarily achieved remission after discontinuing therapy; however, her disease worsened with remittent fever and splenomegaly. Splenic biopsy demonstrated infiltration by abnormal cells, which were positive for CD56 and T cell intracytoplasmic antigen, but negative for CD3 and Epstein-Barr virus (EBV) -encoded RNA. Cytogenetic analysis of bone marrow and lumbar spine tumor revealed common complex karyotype abnormalities. Thus, she was diagnosed with chronic natural killer cell lymphoproliferative disorder (NK-LPD) and finally died of disease progression. The most common type of LPD in methotrexate-related patients with RA is B-lymphoid LPD, whereas NK-LPD is extremely rare. Furthermore, almost all cases of NK-LPD have been reported to be positive for EBV. This is the first case report on a patient with EBV-negative NK-LPD developed during immunosuppressive therapy for RA.

We report a case of solitary fibrous tumor (SFT) originating from the visceral pleura, which presented an extrapleural sign on chest computed tomography (CT) and magnetic resonance imaging (MRI). A 44-year-old woman presented at our hospital for a growing mass visible in chest X-rays. Chest CT and MRI detected a 27×12 mm lesion on the intrathoracic side of the right 3rd intercostal space. The extrapleural signs strongly suggested the tumor to be chest wall origin. However, the tumor was found to be pedunculate with an umbrella-like appearance locating on the visceral pleura of the lung. Histopathological examination demonstrated SFT originating from the visceral pleura.

We present two cases of extensive goblet cell metaplasia in the peripheral lung. The first case was a 72-year-old male with a nodule (12 × 10 mm) detected by CT. Macroscopically, it contained abundant mucin; histopathologically, goblet cells were predominant, whereas ciliated and basal cells were sparse. A KRAS G12V mutation was detected. In the pulmonary background of this case, scattered tiny foci of goblet cell metaplasia were present. The second case was a 71-year-old female with a nodule (7 × 5 mm) detected by CT. It contained abundant mucin, and microscopically, various cell types were intermingled. Although the nodule mainly comprised goblet cells, ciliated and basal cells were also easily identified. No KRAS mutation was found in this patient. Dispersed minute foci of goblet cell metaplasia were identified in the pulmonary background. Therefore, we suspect that airway irritants may have contributed to the changes that occurred in the pulmonary background of both cases. We propose that the tendency of goblet cells to overwhelm other cell types in the metaplastic epithelium may be an indicator of precancerous molecular changes.

An 81-year-old man was referred to our hospital because gastric cancer was detected on screening esophagogastroduodenoscopy. Surgical resection of the tumor was performed. It was 25 × 20 mm in size and swollen lymph nodes were present nearby. Lymphadenectomy was also performed. Histopathologically, the tumor reached the proper muscle layer via venous invasion. There were three components that constituted the tumor, that is, 40% of mass was invasive micropapillary carcinoma (IMPC), 40% was papillary adenocarcinoma and 20% tubular adenocarcinoma. Vascular invasion was prominent. Immunohistochemistry revealed that the tumor showed an entirely intestinal mucin phenotype, being positive only for CD10 and negative for MUC2, MUC5AC, and MUC6. HER2 staining score ranged from 2+ to 3+, depending on the components described above. HER2 gene amplification was present in all the components according to dual-color in situ hybridization. The metastatic lymph nodes were similar to the primary site in morphology and immunohistochemistry, but HER2 amplification was higher in the lymph nodes. The IMPC component with HER2 amplification is rarely seen and its positivity for CD10 is an unexpected finding for gastric IMPC. Hence, this is a highly unusual case judging by the literature; further studies are needed to clarify the nature of gastric IMPC.

A 38-year-old male was admitted to our hospital due to upper abdominal pain. Computed tomography revealed a hepatic angiomyolipoma (AML; 10.5 × 9.5 × 7.0 cm in size), which had ruptured into the space between the liver and the diaphragm. Following transcatheter arterial embolization, surgical resection was performed. The tumor consisted of epithelioid cells (50-60%), mature fat (40-50%), and thickened-wall blood vessels. Considering the amount of epithelioid cells and their positivity for E-cadherin and β-catenin, the tumor was diagnosed as hepatic epithelioid AML. Cases of ruptured hepatic AML are rare. To the best of our knowledge, this is the sixth case reported in the English literature.

An extremely rare case of anterior mediastinal mature teratoma with almost complete gastrointestinal and bronchial walls is described. A 65-year-old woman presented with left precordial pain. Chest computed tomography showed a huge anterior mediastinal tumor, 15 cm × 21 cm, occupying the left thoracic cavity. Post-resection histopathological examination confirmed the diagnosis of mature teratoma and demonstrated almost complete gastrointestinal and bronchial walls. Although mature teratomas of the ovary and sacrococcygeal area are known to rarely contain organoid structures with various degrees of differentiation, this is the first case of an anterior mediastinal mature teratoma that contained well-developed organoid structures.

An asymptomatic 26-year-old man received an annual medical check-up, and chest X-ray showed a protrusion of the aortopulmonary window. Chest computed tomography (CT) revealed an anterior mediastinal tumor and cysts with thin wall and septum enhancement. The preoperative diagnosis was cystic thymoma or malignant lymphoma. We performed total resection of the tumor through a median sternotomy. The pathological findings revealed seminoma, positive for c-kit stain, and multilocular thymic cysts. Cysts were lined by normal squamous epithelium and no seminoma cells were located on their surface. So, cysts were probably secondary changes caused by seminoma cells themselves or inflammatory stimulations. No invasion to adjacent structures was seen. After the surgery, testicular ultrasound imaging and abdominal, pelvic, and cerebral CT showed no apparent tumor or enlarged lymph nodes; however, an abnormal uptake in the right mesenteric lymph node was pointed out by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan. The patient received four courses of bleomycin, etoposide, and cisplatin (BEP) as adjuvant chemotherapy. Follow-up PET scan revealed no uptake in the right mesenteric lymph node. To date, no recurrence or metastasis has been identified for 16 months.

An extremely rare case of non-mucinous lepidic-predominant invasive adenocarcinoma (LPA) showing extensive aerogenous spread with a pneumonic presentation is reported. A 73-year-old woman was referred to our hospital because of an infiltrative shadow on chest xray. Chest computed tomography revealed extensive ground glass opacities in the right lower lobe, which was accompanied by infiltrative shadow with a pneumonic presentation. Invasive mucinous adenocarcinoma was presumed, and a partial resection of the right lower lobe was done. Histopathological examination revealed lepidic growth-predominant invasive adenocarcinoma with Clara type tumor cells, and there were innumerable aerogenous metastases also consisting of Clara cells. Because Alcian Blue and periodic acid-Schiff staining disclosed no mucus, the tumor was diagnosed as a non-mucinous LPA. The patient showed a poor response to 5 courses of pemetrexed, and she died one year after the diagnosis due to cancer progression. Nonmucinous LPA showed a rare presentation characterized by extensive aerogenous spread followed by a poor prognosis.

An extremely rare case of stromal micropapillary predominant lung adenocarcinoma is presented in this study. A 70‐year‐old woman visited our hospital because of an abnormal shadow on chest X‐ray. Chest computed tomography revealed a nodule in the left lower lobe and a mass in the left upper lobe. She underwent an exploratory thoracotomy owing to the suspicion of advanced lung cancer. Pathological examination of the left lower lobe nodule revealed tumour cells with more than half the tumour cells showing stromal micropapillary pattern (SMP), consisting of tumour cells invading the fibrotic stroma. In general, micropapillary adenocarcinomas in the lung form an aerogenous micropapillary pattern (AMP), in which tumour cells float in alveolar spaces. Because the prognosis of SMP lung adenocarcinomas is known to be worse than that of AMP lung adenocarcinomas and have a high frequency of epidermal growth factor receptor mutations, the discrimination of SMP from AMP is important for both pathologists and clinicians.

Adenosquamous lung carcinoma (AdSqLC) has a worse prognosis than adenocarcinoma (ADC) or squamous cell carcinoma (SQCC). Micropapillary pattern in lung ADC is an additional poor prognostic factor. We describe a rare case of AdSqLC with epidermal growth factor receptor (EGFR) mutation in both the micropapillary-ADC and SQCC components, showing long-term response to gefitinib. A 60-year-old woman underwent right lower lobectomy for primary lung cancer. Histopathological examination demonstrated adenosquamous carcinoma comprising micropapillary-ADC and moderately differentiated SQCC. EGFR exon 19 deletions mutation was detected in both the ADC and SQCC components. Gefitinib was administered for multiple metastatic recurrences on bilateral lung, resulting in remarkable shrinkage of visible lesions. The efficacy of gefitinib lasted for 31 months after the induction. AdSqLCs harbouring the EGFR mutation in both the ADC and SQCC components may well benefit from EGFR tyrosine kinase inhibitors, especially when they contain micropapillary-ADC component that correlates with frequent EGFR mutations.

A case of sarcomatoid malignant pleural mesothelioma showing extremely rare growth pattern is described. A 63‐year‐old man presented to our hospital with left pleural effusion. A computed tomography (CT) scan of the chest showed diffusely thickened left visceral and parietal pleura associated with intermingled pulmonary infiltrative shadowing. Biopsy of the pleura under general anaesthesia confirmed the diagnosis of sarcomatoid malignant pleural mesothelioma. The patient underwent left extra‐pleural pneumonectomy. Histopathologically, the sarcomatoid spindle tumour cells changed their morphology to polygonal cells in the pulmonary parenchyma and grew upwards, filling the alveolar space without the destruction of its septa, showing an alveolar‐filling growth pattern. The current report indicates a case of sarcomatoid pleural mesothelioma that shows an alveolar‐filling growth pattern, despite having not been thoroughly categorized in the World Health Organization (WHO) classification.

The degree of leaning of the Electro-Static Discharge (ESD) wave form (hereinafter referred as RON) of ESD protection parameters is closely related to the internal core circuit damage. Accurate measurement of RON requires stable short calibration with Transmission Line Pulse (TLP). In particular, for the high-precision ESD design of the thin gate oxide transistor in the most advanced technology, the high accuracy RON measurement of TLP is required. During short calibration, we found the contact resistance between the packaged sample and integrated circuit (IC) socket varied depending on the calibration current. Scanning Electron Microscope (SEM) analysis of contacts made it clear.

Amyloidosis in non-Hodgkin's lymphoma (NHL) is known to be of the AL type, and AA-type amyloidosis in NHL is extremely rare. Herein is reported an autopsy case of follicular lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL) in a relapse associated with systemic AA amyloidosis. CMV infection in an immunocompromised state with chemotherapy against DLBCL may have been involved in amyloid accumulation. The serum amyloid A (SAA)1 gene polymorphism, SAA1.2/1.3, might have also been another factor in this case, considering the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis.

Uroplakin II antibody is exclusively specific for urothelial carcinoma. Nonurothelial carcinoma has not been reported to be immunoreactive for uroplakin II. In the present study, we hypothesized that breast carcinoma showing apocrine differentiation, such as invasive pleomorphic lobular carcinoma (IPLC) and apocrine carcinoma (AC), stains positive for uroplakin II. We identified 6 cases of IPLC between 2000 and 2014 by searching a computerized pathological database. We randomly selected 10 cases of each classic invasive lobular carcinoma (cILC) and AC and five cases of apocrine metaplasia (AM) that coexisted in a surgically resected breast carcinoma specimen. Immunohistochemistry was performed for uroplakin II, GATA3, CK7, CK20, and other representative markers positive for urothelial carcinoma. All cases of IPLC, AC, and AM, except those of cILC, showed immunoreactivity for uroplakin II. Poorly differentiated urothelial carcinoma sometimes shows similar morphology to IPLC with the following immunophenotype: CK7+, CK20−, GATA3+, and uroplakin II+. In the present study, this immunophenotype was observed in all the cases of IPLC and AC. Therefore, when studying metastatic, poorly differentiated carcinoma showing the aforementioned immunophenotype, we should consider the possibility of it being IPLC in addition to metastatic urothelial carcinoma.

Cytological features of gastrointestinal stromal tumors (GISTs) have been reported, especially regarding fine-needle aspiration cytology, including immunostaining for c-kit and DOG1. Meanwhile, cytological findings of GISTs on ascites cytology have rarely been reported, which may be owing to the rare appearance of GIST tumor cells in ascites. Herein, we present a 66-year-old woman who had disseminated GISTs in the abdomen. The GIST tumor cells appeared sparsely in the ascites smear cytology using ascites obtained at the time of autopsy. Even when widespread intra-abdominal dissemination takes place, GISTs may be hard to detect in ascites smear cytology, based on the experience of this case. However, immunohistochemistry of DOG1 using a cell block preparation was found to clearly visualize the GIST tumor cells, although they were sparsely present. Immunostaining of c-kit did not provide as clear an identification of the tumor cells as DOG1 did. When suspicious about GISTs, it is wise to prepare a cell block to make it possible to visualize the tumor cells immunohistochemically.

Bronchial surface epithelium (BSE)-type lung adenocarcinoma is a subtype of non-terminal respiratory unit (TRU)-type lung adenocarcinoma originating in the bronchial surface epithelium. However, there are few known cases of BSE-type adenocarcinoma with marked expression of thyroid transcription factor-1 (TTF-1). This paper describes a very rare case of KRAS mutation-positive BSE-type adenocarcinoma that exhibited strong expression of TTF-1 that was putatively involved in oncogenesis. An 84-year-old woman, a never smoker, was referred to our hospital because of an abnormal chest radiograph. Chest computed tomography (CT) showed a solid mass lesion, 15 mm × 10 mm, with a relatively smooth margin in the left upper lobe. The patient underwent partial resection of the left upper lobe for strongly suspected lung cancer with a clinical stage of cT1aN0M0. Histopathological findings showed continuous migration of papillary, hyperplastic, atypical columnar tumor cells originating from normal bronchial surface epithelium, leading to a diagnosis of BSE-type adenocarcinoma. TTF-1 was strongly expressed in almost 100% of the tumor cells, which tested positive for the KRAS mutation. TTF-1 has recently attracted attention as an oncogene, and it is purportedly involved in the carcinogenesis and survival of lung adenocarcinoma cells. There is typically an inverse correlation between the respective expressions of KRAS and TTF-1, but in the present study, they appeared simultaneously and were both putatively involved as oncogenic driver alterations. This case is important in that it sheds some light on the largely unknown pathogenic mechanism of BSE-type adenocarcinoma.

Metastasis rarely occurs in the palatine tonsils. Among primary pulmonary carcinoma subtypes, small cell carcinoma more frequently metastasizes to this site. Herein, we present an exceedingly rare case of a small pulmonary adenocarcinoma that metastasized to the cervical lymph nodes and the right palatine tonsil in a 62-year-old man. In spite of the small size of the primary site, such extensive metastasis may have occurred because of the invasive micropapillary carcinoma pattern seen in the metastatic sites. The manner of metastasis to the palatine tonsil was considered retrograde lymphatic metastasis originating from carcinoma cells in the cervical lymph nodes. Furthermore, Pagetoid spread was observed at the palatine tonsil. Although there have been only a few cases showing retrograde lymphatic metastasis and Pagetoid spread at the metastatic site, we should be careful when speculating about the primary site based on such metastatic sites, especially when dealing with a biopsy sample exhibiting Pagetoid spread.

Angiomyolipoma with epithelial cysts (AMLEC) is a distinctive variant of angiomyolipoma characterized by grossly apparent epithelial cysts and a cellular, müllerian-like subepithelial stroma. Some authors suspect that the epithelial cysts mainly represent dilated entrapped native renal collecting duct epithelium, while other authors think that they represented true epithelial differentiation of the AML. Recently, it has been reported that obvious immunolabeling of melanocytic markers such as Melan A and HMB45, which are often immunolabeled in classical angiomyolipoma, are present in epithelial cysts in cases of AMLEC. Here, we report the case of a 43-year-old Japanese woman with AMLEC, and attempt to elucidate the significance of melanocytic marker immunolabeling in the cyst’s epithelium. In the present case, Melan A was labeled in the cyst’s epithelium, and was thought to reflect its labeling in renal tubules existing in the renal parenchyma outside the tumor. This finding may indicate that the cyst epithelium is derived from entrapped renal tubules inside the AML. Non-immunolabeling of the estrogen and progesterone receptors in the cyst epithelium may also suggest that the cyst epithelium is not neoplastic, in contrast to their labeling in neoplastic cells existing in cyst wall. Further examination, such as molecular analysis, is needed to determine whether these epithelial cysts is neoplastic or non-neoplastic.

The predominance of clear cells in mucoepidermoid carcinomas (MEC) is rare, and cases in which this occurs are termed clear cell variants of MEC. We present a case of a 70-year-old woman complaining of a right buccal mucosal mass, which had increased in size over 1 year. Histological examination revealed the mass to be composed predominantly of clear tumor cells, with mucin-containing cells and intermediate cell-like cells. Immunohistochemistry indicated that the tumor was positive for CK5/6 and p63, but negative for myoepithelial markers such as S-100 protein, αSMA, and calponin. These findings ruled out the possibility of a clear cell myoepithelial carcinoma, which is the most frequently observed type of salivary carcinoma composed predominantly of clear cells. However, it is difficult to distinguish between clear cell variants of MEC and hyalinizing clear cell carcinoma. Therefore, we performed fluorescence in situ hybridization to determine whether MAML2 rearrangement had occurred in this mass. Direct sequencing of the RT-PCR product demonstrated CRTC1-MAML2 fusion between exon 1 of CRTC1 and exon 2 of MAML2. Thus, the diagnosis of clear cell variant of MEC was confirmed. This is the first report of CRTC1-MAML2 fusion gene detection in a clear cell variant of MEC.

Primary sarcomas of the breast are rare, accounting for less than 1% of all breast neoplasms. Leiomyosarcoma is one of the least common breast sarcoma subtypes, and less than 50 cases of primary breast leiomyosarcomas have been reported in the English literature. In other types of leiomyosarcoma, osteoclastic giant cells (OGCs) are occasionally admixed with tumor cells; however, this is rarely seen in primary breast leiomyosarcoma. We herein present the case of a 50-year-old woman with OGC-containing primary breast leiomyosarcoma whose tumor cells showed positive immunostaining for receptor activator of NF-κB ligand (RANKL). The presence of OGCs in tumors generally indicates tumor aggressiveness. This is true for leiomyosarcoma of the soft tissue and might be true for leiomyosarcoma of primary breast origin. Regarding RANKL expression, in giant cell tumor of bone (GCTB) in which OGCs expressing RANK were abundant, tumor cells are known for expressing RANKL. Therapy targeting RANKL decreases the number of tumor cells of GCTB. Our findings are clinically relevant as they indicate that RANKL expression should be investigated in various tumors containing OGCs. This might lead to the development of future molecule-targeted therapy.

Phosphaturic mesenchymal tumors (PMT) are the most common cause of tumor-induced osteomalacia (TIO) related to mesenchymal neoplasms. The lineage of differentiation of PMTs has not been elucidated in existing literature. Fourteen cases of PMT were analyzed for this study to elucidate its lineage. We used vascular and/or lymphatic endothelial markers for the immunohistochemical analysis, which included CD31, CD34, factor VIII-related antigen, podoplanin, Freund’s leukemia integration site 1 (FLI1), and avian v-ets erythroblastosis virus E26 oncogene homolog (ERG). FLI1 and ERG were stained in all cases with proportion of immunopositive tumor cells largely more than 50 %; staining intensity was moderate or strong for both FLI1 and ERG. The tumor cells were stained with CD31 and/or CD34, with significantly less staining than observed for FLI1 and ERG. The tumor cells were completely immunonegative for factor VIII-related antigen and podoplanin. FLI1 and ERG are known to have considerable specificity to endothelial cells; ERG is more widely equipped in surgical pathology laboratories than FLI1. We concluded that ERG (or FLI1 if available) is useful marker for the diagnosis of PMT, and that PMTs may have an endothelial cell lineage.

Phosphaturic mesenchymal tumor (PMT) has been elucidated as a cause of tumor-induced osteomalacia (TIO) associated with mesenchymal neoplasm. TIO is associated with the production of phosphatonins, such as fibroblast growth factor 23 (FGF23), which participate in phosphate homeostasis. Fibroblast growth factor receptor 1 (FGFR1) is a known receptor of FGF23, and it was recently found that the fibronectin 1 (FN1)-FGFR1 fusion gene is present in 60% of PMT cases. Immunohistochemical evaluation of FGFR1 expression in PMT has not been reported till date. We analyzed 11 cases of PMT in this study and found that 36% of cases (4/11 cases) exhibited cytoplasmic and membranous staining with strong intensity, and 64% of cases (7/11 cases) exhibited cytoplasmic dot-like staining with moderate to weak intensity. The aforementioned 36% of cases may reflect the presence of the FN1-FGFR1 fusion gene, as the FN1 promoter enhances FGFR1 expression. Although FGFR1 signaling increases FGF23 expression in an autocrine/paracrine loop, FGF23 serum level does not correlate with FGFR1 membranous expression (staining with strong intensity). Thus, we speculate that important factors other than FGFR1 are involved in the tumor biology of PMTs overexpressing FGF23.

Recognizing histological variants in urothelial carcinoma (UC) is important because some may be associated with different clinical outcomes and/or therapeutic approaches; being aware of unusual histological variants may also be crucial in preventing diagnostic misinterpretations. Histological variants based on cytoplasmic features, such as clear-cell, plasmacytoid, rhabdoid, and lipoid-rich variants, are described in invasive UC; however, these cytoplasmic features are not formally defined and not usually encountered in non-invasive UC. Oncocytic cytoplasm has not been well described in either invasive or non-invasive UC. Herein, we report an exceedingly rare case of UC with oncocytic features arising in the right renal pelvis, which presented a diagnostic challenge in urine cytology due to the relatively low nuclear-to-cytoplasmic ratio; however, it could definitively be diagnosed using histological specimens. UC diagnosis is based on the presence of papillary architecture and widespread p53 nuclear accumulation, suggesting malignancy. An oncocytic tumor is generally considered to be not actively dividing, as shown by the low Ki-67 labeling index in this case. In spite of the low proliferative activity, the possibility of intravesicle recurrence (IVR) should be considered since positive preoperative cytology of upper tract UC is a risk factor for IVR after nephroureterectomy.