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.

Neoadjuvant imatinib treatment and laparoscopic anus-preserving surgery for a large gastrointestinal stromal tumor of the rectum.

BACKGROUND: Resection of a gastrointestinal stromal tumor (GIST) of the rectum can be difficult because of the particular location in the pelvis, and a large rectal GIST often requires abdominoperineal resection. Recent reports demonstrate that neoadjuvant imatinib treatment improves surgical outcomes in patients with a rectal GIST, and there are only a few reports of the effectiveness of laparoscopic surgery for a rectal GIST. CASE PRESENTATION: A 46-year-old man was found to have a rectal GIST that measured 80 mm and was located on the anterior wall of the lower rectum. After 6 months treatment with imatinib, the tumor decreased in size to 37 mm, and laparoscopic low anterior resection was performed. The patient is currently alive without any evidence of recurrence 37 months after surgery. CONCLUSIONS: Neoadjuvant imatinib should be a treatment of choice for a large rectal GIST. When marked tumor shrinkage is achieved, laparoscopic surgery may be the preferred procedure.

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.

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.

High-grade fetal adenocarcinoma of the lung is a tumour with a fetal phenotype that shows diverse differentiation, including high-grade neuroendocrine carcinoma: a clinicopathological, immunohistochemical and mutational study of 20 cases.

AIMS: High-grade fetal adenocarcinoma (H-FLAC) is a rare variant of pulmonary adenocarcinoma; this study aims to elucidate its clinicopathological features and genetic abnormalities. METHODS AND RESULTS: Clinicopathological, immunohistochemical and mutational analyses were performed on 20 surgically resected lung cancers that showed H-FLAC histology in various proportions. These tumours predominantly occurred in elderly males and in 10 patients who were heavy smokers. Four cases were pure H-FLAC, and 16 cases were mixed H-FLAC, which were found to be combined with conventional-type adenocarcinoma (15 cases), large-cell neuroendocrine carcinoma (three cases), small-cell carcinoma (one case), enteric adenocarcinoma (two cases), choriocarcinoma (two cases), and a solid-clear cell pattern (seven cases). The fetal phenotype and diverse differentiation were supported by the immunoexpression of α-fetoprotein (95%), thyroid transcription factor-1 (TTF-1) (50%), neuroendocrine markers (30-45%), proneural markers (50-69%), and CDX2 (40%). Except for TTF-1 expression (pure H-FLACs, 0%; mixed H-FLACs, 63%), there were no significant differences in histological or immunohistochemical findings between pure and mixed H-FLACs. EGFR, KRAS, BRAF and PIK3CA mutations were identified in 20%, 0%, 0% and 7% of the tumours, respectively. CONCLUSIONS: Lung adenocarcinomas with H-FLAC features possess the potential for multidirectional differentiation, and are not strongly associated with known major driver gene mutations.

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.

Extensive goblet cell metaplasia of the peripheral lung may harbor precancerous molecular changes: comparison of two cases.

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.

Two independent families with strongly suspected hereditary diffuse gastric cancer based on the probands' endoscopic findings.

Hereditary diffuse gastric cancer (HDGC) is the most famous of hereditary gastric cancer syndromes with an autosomal dominant inheritance pattern, and its diagnosis can be made by identifying a pathogenic germline variant in CDH1. We report two independent families that were strongly suspected of having HDGC based on endoscopic findings (multiple tiny, pale areas) obtained in the probands; the probands were pathologically diagnosed as having signet ring cell carcinoma (SRCC) and were genetically confirmed to have a pathogenic CDH1 germline variant. Although the updated International Gastric Cancer Linkage Consortium (IGCLC)'s clinical guidelines for HDGC (2015) state that screening/surveillance endoscopy should be performed (Cambridge protocol), the endoscopic findings obtained in the two presently reported families suggest that pale areas should be suspected as indicating the presence of SRCCs, and biopsies should be performed in addition to obtaining a precise family history in cases suspected of having HDGC.

[Case of pancreatic mucosa-associated lymphoid tissue (MALT) lymphoma].

A 77-year-old woman underwent abdominal ultrasonic diagnosis in a screening test for diabetes mellitus. A 65 x 45 mm tumor with low echo level was revealed and located from the uncinate process of the pancreas to the body. Contrast-enhanced computed tomography demonstrated the pancreas had a low density area in the arterial phase and a comparable area in the equilibrium phase, compared with the parenchyma of the normal pancreas. Gallium-scintigraphy showed strong accumulation, consistent with the tumor. Mucosa-associated lymphoid tissue (MALT) lymphoma was diagnosed by endosonography-guided fine-needle aspiration biopsy (EUS-FNAB). Complete remission was achieved after radiation therapy.

[Retroperitoneal fibrosis and Castleman disease in two patients with high IgG4 levels].

With the cumulative increase in the number of autoimmune pancreatitis cases, the disease is now widely accepted as a symptom of IgG4-related systemic disease. We recently experienced two cases of retroperitoneal fibrosis and Castleman disease presenting high IgG4 levels without evident pancreatic lesions. Both patients were successfully treated with steroid therapy. It is necessary to acknowledge that retroperitoneal fibrosis and Castleman disease, with or without pancreatic lesions, may have aspects of IgG4-related systemic disease and that the measurement of serum IgG4 and tissue immunostaining for IgG4 should be considered for diagnosing and treating the conditions.

Locally infiltrative inflammatory fibroid polyp of the ileum: report of a case showing transmural proliferation.

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.

[A case of Castlemans disease (plasma cell type) in which autoimmune pancreatitis developed 6 years later].

In 1998 a 74-year-old man, he had a medical checkup and mediastinal and hilar lymph node hyperplasia were discovered. Since the lymph nodes showed a tendency to increase in size, mediastinal lymph node biopsy was performed in the following year. Castlemans disease was diagnosed, and he was followed up. In 2005, autoimmune pancreatitis (AIP) developed. At this time, the mediastinal lymph node that had been biopsied was stained with anti-IgG4 antibody. Further examinations on pancreatic lesions associated with Castlemans disease and AIP are necessary in relation to IgG4-related systemic diseases.

HIF-1α, MDM2, CDK4, and p16 expression in ischemic fasciitis, focusing on its ischemic condition.

Ischemic fasciitis is a benign myofibroblastic lesion, occurring in the sacral region or proximal thigh of elderly or bedridden individuals. The pathogenesis of ischemic fasciitis is thought to be based on ischemic condition; however, it has never been demonstrated. In this study, we examined the expression of ischemia-associated proteins in ischemic fasciitis by immunohistochemical and genetic methods. Specifically, this study aimed to reveal the expression of HIF-1α, MDM2, CDK4, p16, and gene amplification of MDM2 gene. Seven cases of ischemic fasciitis from among the soft-tissue tumors registered at our institution were retrieved. Histopathological findings were as follows: poorly demarcated nodular masses, a proliferation of spindle-shaped fibroblastic or myofibroblastic cells with oval nuclei and eosinophilic or pale cytoplasm, zonal fibrinous deposition, pseudocystic degeneration, granulation-like proliferation of capillary vessels, ganglion-like cells, myxoid or hyalinized stroma, and chronic inflammatory infiltration. Immunohistochemically, the spindle cells were positive for HIF-1α (7/7 cases), MDM2 (4/7 cases), CDK4 (4/7 cases), p16 (7/7 cases), p53 (2/7 case), cyclin D1 (7/7 cases), and alpha-smooth muscle actin (6/7 cases). Neither MDM2 gene amplification nor USP6 gene split signal was detected in any case. Overexpression of the above proteins may be associated with the pathogenic mechanism of ischemic fasciitis. It is noted that the immunohistochemical positivity of MDM2, CDK4, and p16 do not necessarily indicate malignant neoplasm such as dedifferentiated liposarcoma.

Spontaneous rupture of a necrotic hepatic angiosarcoma: findings on dual-phase computed tomography and angiography.

We present dual-phase computed tomographic (CT) and angiographic findings of a ruptured hepatic angiosarcoma. These tumors can be divided into two types: those with and those without gross central necrosis with hemorrhage. In our case, the tumor had gross central necrosis, and CT and angiographic findings showed a small number of areas with a centripetal enhancement pattern and the rest of the tumor with avascular areas. We found that dual-phase CT and angiographic findings are able to distinguish angiosarcoma, which mimics a hemangioma, as these lesions show avascular areas that reflect a mass with gross central necrosis.

Uroplakin II Expression in Breast Carcinomas Showing Apocrine Differentiation: Putting Some Emphasis on Invasive Pleomorphic Lobular Carcinoma as a Potential Mimic of Urothelial Carcinoma at Metastatic Sites.

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.