Rare Anal Canal Cancer with Secondary Extramammary Paget's Disease (Pagetoid Spread) Complicated by Squamous Cell Carcinoma of the Skin.

A 91-year-old man had a node and erythema in the anal area resistant to treatment. A biopsy of the node in the anus showed atypical cells developing as Paget's disease, and staining revealed that the cells were CK7-positive, CK20-positive, and GCDFP15-negative. Therefore, tumor invasion with pagetoid spread (PS) from the anus to the skin was suspected, and the patient was referred to our department for a close examination and surgical treatment. Lower gastrointestinal endoscopy showed edematous, hemorrhagic mucosa in the anal canal, and he was diagnosed with adenocarcinoma via a biopsy. Additionally, redness and swelling with white moss were observed on the skin around the anus. Biopsy showed that Paget cells were diffusely present in the epithelium, and an image of squamous cell carcinoma directly under the epithelium was obtained. Taken together, the patient was diagnosed with the invasion of anal canal cancer with PS to the skin, and we performed laparoscopic abdominoperineal resection and skin carcinoma resection in the perineum. The histopathological analysis showed adenocarcinoma invading the external anal sphincter and subcutaneous adipose tissue in the vicinity of the pectinate line of the anal canal. Pagetoid spread of the adenocarcinoma was observed in the epidermis, and the open portion was slightly invaded up to the rectal mucosa. The anal skin region of the adenocarcinoma partially continued to the hair follicles, and it was complicated by squamous cell carcinoma invading the dermis. There are a few reports of anal canal cancer with PS, and the coexistence of adenocarcinoma and squamous cell carcinoma, as seen in the present case, is rare. We report our case together with relevant literature.

[SERTOLI CELL TUMOR OF TESTIS: CASE REPORT].

A 36-year-old male with right scrotal induration visited a local physician and ultrasonography showed a mass in the right testicle. He was referred to our hospital, where an additional ultrasonography examination revealed a 1×1-cm mass with clear borders, a heterogeneous interior, slight hyperintensity, and abundant blood flow in the upper part of the right testis. Contrast-enhanced computed tomography results indicated a massive lesion with an uneven contrast effect in the right testis and no evidence of metastasis, while magnetic resonance imaging showed the tumor with bleeding and internal heterogeneity. All tumor markers were negative. Under a diagnosis of primary germ cell tumor of the testis without metastasis, a high orchiectomy was performed. The pathological diagnosis was sertoli cell tumor. Histopathologically, the tumor was benign and no additional treatment was performed. Three years after the operation, the patient was well and without complications.

[A case of Endocrine Active Retroperitoneal Ganglioneuroma, Difficult to Differentiate From Adrenal Pheochromocytoma].

A 66-year-old woman who had been receiving medication for hypertension and hyperlipidemia was referred to our hospital for evaluation of a left adrenal tumor (12×8 mm) that was incidentally detected on computed tomography. Her 24-hour urinary catecholamine level was elevated, and metaiodobenzylguanidine (MIBG) scintigraphy revealed increased uptake in the area around the left adrenal gland, necessitating laparoscopic adrenalectomy for preoperative diagnosis of left adrenal pheochromocytoma. Intraoperatively, we detected a para-aortic tumor behind the adrenal gland, and this lesion was excised together with the adrenal gland. However, manipulation of the para-aortic tumor led to elevation in the blood pressure to 170 mmHg. Histopathological examination of the resected specimens revealed an adrenocortical adenoma and a para-aortic ganglioneuroma, consisting of ganglion cells, nerve fibers, and Schwann cells. The patient's blood pressure normalized immediately postoperatively, and MIBG scintigraphy revealed a negative result. Endocrine active ganglioneuromas are rare, and to our knowledge, currently only 8 cases (including ours) have been reported in the Japanese and English literature.

[PRIMARY SQUAMOUS CELL CARCINOMA OF THE PROSTATE: A CASE REPORT].

SQUAMOUS CELL CARCINOMA, prostate carcinoma, The patient was a 67-year-old man who visited our hospital with urge incontinence. His serum prostatic specific antigen level was normal (1.191 ng/mL). Digital rectal examination and magnetic resonance imaging suggested common prostatic carcinoma. A transperineal needle biopsy was performed, and the histological diagnosis was squamous cell carcinoma (SCC). The serum SCC-antigen level was normal, and the patient underwent a radical prostatectomy. Computed tomography 15 months later revealed multiple metastases in the lymph nodes. The patient underwent systemic chemotherapy using fluorouracil (5-FU) and cisplatin (CDDP). After 3 courses of chemotherapy, the multiple lymph node metastases could not be detected.

Genomic profiling of the genes on chromosome 3p in sporadic clear cell renal cell carcinoma.

Somatic mutations of the BRCA1 associated protein-1 (BAP1) gene, which maps to 3p21, have been found in several tumors including malignant mesothelioma, uveal melanoma, and renal cell carcinoma (RCC). The role of BAP1 inactivation in tumor development remains unclear. It has been reported that Vhl knock-out mice did not develop RCC, but Vhl knock-out mice with single allele loss of Bap1 in nephron progenitor cells developed RCC, indicating that Bap1 inactivation may be essential in murine renal tumorigenesis. To clarify the role of BAP1 in human RCC development, we performed mutation analyses, including copy number detection of BAP1 and assessment of allelic imbalance using microsatellite polymorphisms on 3p, in 45 RCC samples derived from 45 patients without VHL or BAP1 germline mutation. Additionally, we analyzed the sequences of the VHL, PBRM1, and SETD2 genes, and examined promoter methylation of VHL. Using immunostaining, we also checked for expression of BAP1 protein, which is normally located in the nuclei. None of the RCCs had biallelic deletion of BAP1, but five (11.1%) showed a biallelic mutation (four with a sequence-level mutation with monoallelic loss and one with a biallelic sequence-level mutation); these cells were negative for nuclear BAP1 staining. These patients had worse recurrence-free survival than the patients without a biallelic mutation (p=0.046). However, there were no significant differences in worse outcome by multivariate analysis combined with age, T stage, histological subtype, infiltration and vascular invasion. In 35 RCCs (77.8%), monoallelic loss of BAP1 was accompanied by VHL biallelic mutation or VHL promoter hypermethylation. In five RCCs (11.1%), we detected 3p loss-of-heterozygosity, but the copy number of BAP1 was normal. Surprisingly, nuclear staining of BAP1 was negative in 10 out of 31 tumors (32.3%) with hemizygous normal BAP1, suggesting that haploinsufficiency may relate to RCC development.

[A Case of Retroperitoneal Serous Cyst Treated by Open Fenestration : A Case Report].

A 47-year-old woman came to our hospital with left lower abdominal pain in April 2013. An abdominal computed tomographic (CT) examination revealed left hydronephrosis secondary to a 7 cm retroperitoneal cyst near the left common iliac artery and ureter. Serum tumor markers including CEA, CA19-9, and CA125 were negative. Although CT guided needle aspiration of the cyst successfully relieved severe left flank pain, the cyst again increased in size, causing left hydronephrosis, though examinations for fluid tumor markers and cytology were negative. Two months later, the patient underwent open fenestration. The final pathological results demonstrated a mesothelial cyst without malignant findings. Six months after the operation, the patient was doing well without recurrence of symptoms.

Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type with malakoplakia in the urinary bladder: a case report.

Primary malignant lymphoma of the urinary bladder is a rare disease constituting less than 1% of neoplasms of the urinary bladder. The most prevalent histological subtype is extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma). It is frequently associated with chronic cystitis and predominantly occurs in females. On the other hand, malakoplakia is thought to be a reactive granulomatous lesion occurring most prevalently in the genitourinary tracts. It is frequently found in females and often associated with bacterial infection in immunosuppressive status. Here we report a rare case of concurrent primary MALT lymphoma and malakoplakia in the urinary bladder in a 78-year-old Japanese female. Presumably, both lymphoma and malakoplakia are considered to be involved in the antecedent cystitis and might contribute to the development of the urinary bladder tumor of the patient, leading to the occlusion of the right ureter with subsequent hydronephrosis.

[Leiomyosarcoma of the inferior vena cava: a case report and review].

A 37-year-old woman with an incidentally found abdominal mass was referred to our hospital. A fixed, non-tender mass was palpated in the right upper quadrum of her abdomen. There was no elevation of tumor markers. Computed tomography revealed a mass extending from the hepatic vein level to renal hilar level. The tumor completely obstructed the inferior vena cava (IVC). T1-weighted magnetic resonance imaging (MRI) showed that the mass was isointense with muscles. T2-weighted MRI image with contrast medium demonstrated collateral circulation. Upon diagnosis of the IVC tumor, we removed the right kidney and the tumor en bloc without reconstructing IVC. The tumor diameter was 11.6 × 5.5 × 4.7 cm. Pathological examination established a diagnosis of IVC leiomyosarcoma. She is alive without sign of recurrence after operation for seven months. There were 143 reports of IVC leiomyosarcoma in Japan. In 31% of them, IVC was not reconstructed.

Paratesticular myxoid/round cell liposarcoma harboring type 3 DDIT3-FUS fusion gene: report of a very rare case.

Myxoid/round cell liposarcomas are rare mesenchymal neoplasms. They preferentially occur in the lower extremity, and most of them have type 1 or type 2 DDIT3-FUS fusion gene. We report here a very rare case of myxoid/round cell liposarcoma of the paratesticular region with type 3 DDIT3-FUS fusion gene. A 46-year-old Japanese man noticed a gradually enlarged intrascrotal mass without pain. Surgical resection of 3.4 cm × 2.1 cm oval mass was carried out, and it was located in the right paratesticular region apart from the spermatic cord and epididymis. Histological examination of the tumor revealed ovoid cell proliferation with anastomosing vascular network and scattered lipoblasts. Genetic analysis elucidated that the tumor had a chromosomal translocation, type 3 DDIT3-FUS chimeric gene. The tumor was definitely diagnosed as myxoid/round cell liposarcoma of the paratesticular region.

[Unclassified renal cell carcinoma accompanying pyonephrosis: a case report].

A 73-year-old male, admitted to a local hospital because of fever and consciousness disturbance, was referred to our institute. He had a history of long-term steroid administration and diabetes mellitus. Under diagnosis of severe right pyonephrosis associated with severe inflammatory response syndrome as well as disseminated intravascular coagulopathy, he was transferred to our hospital. Computed tomography and magnetic resonance imaging showed a mass 5 cm in diameter at the right ureteropelvic junction and lymph node swelling at the renal hilum, suggesting obstructive pyonephrosis by a malignant tumor such as renal pelvic cancer. Since the patient failed to respond to conservative medical treatment including polymyxin B hemoperfusion, hemodialysis, and antimicrobials, we performed right nephrectomy. Histopathological examination demonstrated that the tumor obstructing the pelvis arose from the parenchyme under the muscle layer, and was diagnosed as unclassified renal cell carcinoma while the renal pelvic epithelium was normal. Although his general condition and laboratory data transiently improved after nephrectomy, he died of carcinomatous peritonitis 30 days postoperatively. We advocate that, in the case of pyonephrosis with a lesion highly suspected to be an infiltrating neoplasm, nephrectomy is justified as first choice to control the septic condition.

Extra-gastrointestinal stromal tumor of the pelvic cavity: case report.

Extra-gastrointestinal stromal tumors (E-GISTs) not associated with the alimentary tract in the pelvic cavity are extremely rare. We treated a 49-year-old Japanese man with such an E-GIST in the pelvic cavity who underwent an intrapelvic tumorectomy with a total prostatectomy and partial rectum resection. Gross examination of the specimen revealed an 8.1 × 5 × 4 cm white-grayish mass. Histological findings showed uniform spindle cells with scant atypia that formed interlacing bundles or whorl patterns. These neoplastic cells did not invade adjacent organs, including the gut. Immunohistochemical findings revealed that the neoplastic cells were positive for c-kit, CD34, and vimentin. Molecular analysis showed a c-kit mutation at exon 9 with duplication of Ala and Tyr. Our diagnosis was E-GIST, which belongs to the intermediate group of GIST. Following the operation, we administered imatinib mesylate for 6 months. After stopping for 5 months, it was administered again for local recurrence. We are planning our future strategy for this case including surgical resection as necessary.

Primary carcinoid tumor of the urinary bladder with prominent subnuclear eosinophilic granules.

Primary carcinoid tumor of the urinary bladder is a very rare neoplasm. We report here a case of primary carcinoid tumor of the urinary bladder with an unusual cytological feature in a 72-year-old Japanese man. A bladder polypoid mass was incidentally found by ultrasonography during the follow-up of a benign prostate hyperplasia. Histological examination of the transurethrally resected tissue revealed that the upper part of the mass was a tumor showing tubuloglandular anastomosing structures. Most of the tumor cells had peculiar subnuclear eosinophilic granules. The features of the granules were reminiscent of those observed in neuroendocrine cells of the intestine. The tumor cells were immunohistochemically positive for chromogranin A and synaptophysin. The tumor was diagnosed as carcinoid tumor of pure form of the urinary bladder. The lower part of the mass showed the findings of glandular cystitis, as its coexistence with carcinoid tumors of the bladder has often been described in previous reports.

[Metachronous urothelial cancer in bilateral upper urinary tracts and bladder associated with hereditary nonpolyposis colorectal cancer].

A 40-year-old man had undergone right hemicolectomy and sigmoidectomy under the diagnosis of ascending and sigmoid colon cancer and right nephroureterectomy under the diagnosis of right ureteral cancer, in 1997 and in 2002, respectively. In 2007, He visited our hospital with a complaint of bloody stool and hematuria. Colon fiberscopy, ureteropelvicscopy and cystoscopy demonstrated colon cancer, left renal pelvis cancer and bladder cancer, respectively, as diagnosed by biopsies, followed by restative colectomy, left nephroureterectomy and cystectomy. The final histopathological examination showed well differentiated adenocarcinoma (pSM) in the colon, and urothelial carcinoma in the left renal pelvis (pT2) and the bladder (pT1). Since his uncle and elder brother had suffered from stomach cancer and colon cancer, respectively, he was diagnosed with hereditary nonpolyposis colorectal cancer (HNPCC : Lynch syndrome). He has been well doing without recurrence for 3 years after the surgery.

New double embedding technique for specimens of endoscopic submucosal dissection using agarose: comparison with other media.

AIMS: Procedure of endoscopic submucosal dissection (ESD) has been introduced widely for treatment of early gastric cancers. For such specimens, accurate pathological diagnosis, especially concerning depth of the invasion and exposure to margins, is essential to decide on the necessity of additional treatment. Therefore, easy and reliable tissue-processing method for multiple cut specimens is needed. The authors report here a new double embedding technique for specimens of ESD. METHODS: Formalin-fixed whole specimen was superficially wrapped by agarose (the first embedding), and the tissue-agarose block was cut at 2-3 mm intervals. Each cut specimen was laid down with 90° rotation. This procedure permitted 'on edge' embedding of thin tissues in paraffin (the second embedding) and subsequent preparation of perpendicular section to the tissue surface. The authors compared the handleability and stainability among several media including various types of agar, agarose and gelatin for first embedding. A survey by questionnaire was carried out on handleability and/or impression on various tissue-processing steps from pathology technicians. RESULTS: Among the media examined, agarose showed the best solubility in water and the best transparency on several representative stainings. According to the survey, pathology technicians seemed to feel that the present method was better than the usual tissue processing method, especially in shortened time consumption and accuracy of alignment of multiple tissues for ESD specimens. CONCLUSIONS: The present new double embedding technique using agarose provides not only an easy and reliable embedding procedure for technicians but also accurate and exact diagnosis for pathologists.

Solid-pseudopapillary neoplasm of the pancreas with massive central calcification in an old man.

Solid-pseudopapillary neoplasm (SPN) is a rare pancreatic tumor primarily affecting women in their twenties. It is characterized by a well-demarcated or encapsulated mass, indolent behavior and favorable prognosis. Capsular or punctate calcification is occasionally observed. Reported herein is a case of SPN of the pancreas with massive calcification in a 76-year-old Japanese man. Macroscopically, the pancreatic tumor appeared to be a simple calcified nodule, but histological examination revealed that it was an epithelioid tumor with massive calcification. The tumor cells, forming nests and cords, had eosinophilic cytoplasm and small eccentric nuclei. They were immunohistochemically positive for vimentin, CD56 and neuron-specific enolase. Nuclear accumulation of beta-catenin protein and a point mutation of the beta-catenin gene by genomic DNA sequencing confirmed that the tumor was SPN. This is a very rare case of pancreatic SPN with massive calcification in an old man.