Paratesticular dedifferentiated liposarcoma with prominent myxoid stroma: report of a case and review of the literature.

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.

Germinoma with an extensive rhabdoid cell component centered at the corpus callosum.

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.

A clear cell variant of mucoepidermoid carcinoma harboring CRTC1-MAML2 fusion gene found in buccal mucosa: report of a case showing a large clear cell component and lacking typical epidermoid cells and intermediate cells.

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.

Iatrogenic immunodeficiency-associated Epstein-Barr virus (EBV) -negative natural killer cell lymphoproliferative disorder in a patient undergoing rheumatoid arthritis therapy.

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.

[Solitary Fibrous Tumor Originating from the Visceral Pleura Presenting an Extrapleural Sign;Report of a Case].

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.

Breast carcinoma with a predominant duct-replacing component and chondroid matrix production.

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.

Pleomorphic leiomyosarcoma with a dedifferentiation-like appearance in the kidney: case report and literature review.

Although primary leiomyosarcoma of the kidney is extremely rare, it is the most common sarcoma of the kidney. Leiomyosarcoma with a large pleomorphic component is designated as pleomorphic leiomyosarcoma. The pleomorphic component is usually similar to undifferentiated high-grade pleomorphic sarcoma, although it variably expresses smooth muscle markers on immunohistochemistry. In the few reported cases of pleomorphic leiomyosarcoma of the kidney, cases with the pleomorphic component showing distinct nodularity similar to dedifferentiated leiomyosarcoma have not been described, to the best of our knowledge. Herein, we present a case of a 49-year-old woman with pleomorphic leiomyosarcoma in the kidney showing distinct nodularity of smooth muscle marker-expressing pleomorphic cells within a background of classic leiomyosarcoma. Along with the classification as a pleomorphic leiomyosarcoma, suggesting aggressive clinical behavior, the renal origin itself might also be a predictor of poor prognosis, as shown in a previous study. This case also involved concomitant distant metastases, already present during the initial detection of the renal tumor.

E-cadherin-negative acinar cell carcinoma of the pancreas: report of a case showing a solid pseudopapillary growth pattern.

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 ß-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 ß-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.

Cystic apocrine ductal carcinoma in situ with increased EGFR expression, trisomy 7, and associated focal invasion.

A 71-year-old woman was admitted to our hospital with a lump in her right breast. Mammography revealed an internal high-density mass in the lower right breast, which was larger than it was 2 years ago. Considering the findings from ultrasonography, computed tomography, and cytology, an intracystic carcinoma could not be ruled out. The patient underwent excisional biopsy, which revealed an apocrine ductal carcinoma in situ (ADCIS) with focal invasive apocrine carcinoma (IAC). The diagnosis was based on morphology and immunohistochemistry (IHC), which was negative for the estrogen and progesterone receptors, and positive for the androgen receptor. Expression of the human epidermal growth factor receptor 2 and the epidermal growth factor receptor (EGFR) received an immunohistochemical score of 2+. Trisomy of chromosome 7, including multiple CEP 7 and EGFR signals, was observed in ADCIS by fluorescence in situ hybridization (FISH). IAC exhibited similar results for IHC and FISH. This is the first reported case showing trisomy 7 resulting in EGFR copy number gain and increased EGFR expression in ADCIS.

ERG and FLI1 are useful immunohistochemical markers in phosphaturic mesenchymal tumors.

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.

Invasive urothelial carcinoma with chordoid features may be an ominous sign predicting sarcomatoid change: a case report of a bladder carcinoma.

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.

Robust quantitative assessments of cytosine modifications and changes in the expressions of related enzymes in gastric cancer.

BACKGROUND: The rediscovery of 5-hydroxymethylcytosine, the ten-eleven translocation (TET) family, thymine-DNA glycosylase (TDG) and isocitrate dehydrogenase (IDH) have opened new avenues in the study of DNA demethylation pathways in gastric cancer (GC). We performed a comprehensive and robust analysis of these genes and modified cytosines in gastric cancer. METHODS: Liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) was used to assess 5-methyldeoxycytidine (5-mC), 5-hydroxymethyldeoxycytidine (5-hmC), 5-formyldeoxycytidine (5-fC) and 5-carboxyldeoxycytidine (5-caC) quantitatively in tumorous and non-tumorous regions of GCs; [D2]-5-hmC was used as an internal standard. Expression levels of the genes TET1, TET2, TET3, TDG, IDH1 and IDH2 were measured using a real-time reverse transcription polymerase chain reaction (RT-PCR) and were compared to the clinical attributes of each case. Using HEK293T cells the effects of introducing plasmids containing full-length TET1, TET2, and TET3 and 7 variants of the TET2 catalytic domain were evaluated in terms of their effect on cytosine demethylation. RESULTS: LC-MS/MS showed that 5-hmC was significantly decreased in tumorous portions. 5-mC was also moderately decreased in tumors, while 5-fC and 5-caC were barely detectable. The expressions of TET1, TET2, TET3, TDG and IDH2, but not IDH1, were notably decreased in GCs, compared with the adjacent non-tumor portion. TET1 expression and the 5-hmC levels determined using LC-MS/MS had a significantly positive correlation and TET1 protein had a greater effect on the increase in 5-hmC than TET2 and TET3 in HEK293T cells. CONCLUSIONS: The loss of 5-hmC and the down-regulation of TET1-3, TDG and IDH2 were found in GCs. The loss of 5-hmC in GCs was mainly correlated with the down-regulation of TET1.

Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: a single-cell MALDI-IMS approach.

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.

A signet-ring cell melanoma arising from a medium-sized congenital melanocytic nevus in an adult: A case report and literature review.

Patients with congenital nevus, especially giant congenital melanocytic nevus (CMN) measuring >20 cm, are known to be at elevated risk of developing melanomas, especially during the first and second decades of life. Melanomas rarely develop in patients with small and medium-sized CMNs, but if they do, they occur during the fourth and fifth decades of life. We present a case of a rapidly enlarging signet-ring cell melanoma (over 3 months) that arose from a medium-sized CMN in a 57-year-old Japanese man. Only 11 other cases of signet-ring cell melanomas at the primary site have been reported. On the basis of morphology alone, it is difficult to diagnose a nodule appearing in a CMN as a signet-ring cell melanoma, because even a benign melanocytic nevus can appear as signet-ring cell morphology. Moreover, a rapidly growing proliferative nodule (PN) more often develops in a CMN than melanoma; PNs may at times exhibit enough atypia to be comparable to melanomas. In our case, loss of p16 expression in the melanoma distinguished it from the nevus cells and was helpful in making the correct diagnosis. Clinical information, such as the patient's age, was also useful in establishing the diagnosis.

A case of cord capillary hemangioma of the spleen: a recently proven true neoplasm.

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.

Primary leiomyosarcoma of the breast with prominent osteoclastic giant cells: A case expressing receptor activator of NF-κB ligand (RANKL).

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.

Methotrexate-associated lymphoproliferative disorder presenting as extranodal NK/T-cell lymphoma arising in the lungs.

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.

Intimal sarcoma of the abdominal aorta with platelet-derived growth factor receptor α overexpression and amplification in mural invasive cells and pulmonary metastatic cells but not in intimal spreading cells.

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.

Acquired cystic disease-associated renal cell carcinoma with a focal sarcomatoid component: Report of a case showing more pronounced polysomy of chromosomes 3 and 16 in the sarcomatoid component.

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has recently been established. Herein we report the sixth case of ACD-associated RCC with a sarcomatoid change. The patient was a 77-year-old man who regularly underwent hemodialysis for 14 years due to chronic renal failure resulting from IgA nephropathy. On computed tomography, a large right RCC was observed with contrast enhancement in the arterial phase. A nodular protrusion into the perirenal fat was detected. Right nephrectomy was performed under laparoscopy. Surgically resected specimens revealed a tan-to-yellow tumor (95 × 75 × 55 mm) with a whitish nodule (20 × 15 × 15 mm) invading into the perirenal fat. Histopathologically, the large carcinoma component of the tumor displayed a cribriform or microcystic growth pattern with deposition of oxalate crystals. The whitish nodule corresponded to the sarcomatoid component, and the spindled and pleomorphic tumor cells showed diffuse positivity of p53 on immunohistochemistry. Fluorescence in situ hybridization revealed trisomy of chromosomes 3 and 16 in the carcinoma component, as was expected from the literature. In addition, increased polysomy of these chromosomes was also observed in the sarcomatoid component. This finding may be related to the development of the sarcomatoid component along with the TP53 mutation.

Gastric carcinoma with an invasive micropapillary carcinoma component showing HER2 gene amplification and CD10 expression: a case report and review of the literature.

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.