Acute large-vessel occlusion due to an infected thrombus formation induced by invasive sphenoid sinus aspergillosis: illustrative case.

BACKGROUND: The authors describe a rare case of acute large-vessel occlusion due to an infected thrombus formation that was induced by invasive sphenoid sinus aspergillosis. OBSERVATIONS: An 82-year-old man with a history of immunoglobulin G4-related disease and long-term use of steroids and immunosuppressants was admitted to the authors' hospital with severe right hemiparesis. Cerebral angiography revealed occlusion of the left internal carotid artery (ICA). He underwent thrombectomy, resulting in successful recanalization. However, severe stenosis was evident in the left ICA cavernous segment. Pathological analysis of the retrieved thrombus identified Aspergillus. Postoperative magnetic resonance imaging revealed sinusitis in the left sphenoid sinus as a possible source of the infection. The patient's general condition deteriorated during the course of hospitalization due to refractory aspiration pneumonia, and he died 46 days after thrombectomy. Pathological autopsy and histopathological investigation of the left ICA and the left sphenoid sinus showed that Aspergillus had invaded the wall of the left ICA from the adjacent sphenoid sinus. These findings indicate a diagnosis of acute large-vessel occlusion due to infected thrombus formation induced by invasive sphenoid sinus aspergillosis. LESSONS: Pathological analysis of a retrieved thrombus appears useful for identifying rare stroke etiologies such as fungal infection.

A case of solitary neurofibroma in the maxillary gingiva.

Neurofibromas are benign tumors. They are known to be a manifestation of von Recklinghausen's disease (neurofibromatosis type 1) and tend to be generalized and rarely solitary. In this report, we present a case of solitary neurofibroma in the maxillary gingiva. A 39-year-old woman presented with a chief complaint of swollen gingiva. There were no special findings in her medical or family history. After a biopsy was performed under local anesthesia and a diagnosis of neurofibroma was made, tumor resection was performed under general anesthesia. The patient's progress was good, with no recurrence.

Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders.

Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) is an autoimmune astrocytopathic disease pathologically characterized by the massive destruction and regeneration of astrocytes with diverse types of tissue injury with or without complement deposition. However, it is unknown whether this diversity is derived from differences in pathological processes or temporal changes. Furthermore, unlike for the demyelinating lesions in multiple sclerosis, there has been no staging of astrocytopathy in AQP4-IgG+NMOSD based on astrocyte morphology. Therefore, we classified astrocytopathy of the disease by comparing the characteristic features, such as AQP4 loss, inflammatory cell infiltration, complement deposition and demyelination activity, with the clinical phase. We performed histopathological analyses in eight autopsied cases of AQP4-IgG+NMOSD. Cases comprised six females and two males, with a median age of 56.5 years (range, 46-71 years) and a median disease duration of 62.5 months (range, 0.6-252 months). Astrocytopathy in AQP4-IgG+NMOSD was classified into the following four stages defined by the astrocyte morphology and immunoreactivity for GFAP: (i) astrocyte lysis: extensive loss of astrocytes with fragmented and/or dust-like particles; (ii) progenitor recruitment: loss of astrocytes except small nucleated cells with GFAP-positive fibre-forming foot processes; (iii) protoplasmic gliosis: presence of star-shaped astrocytes with abundant GFAP-reactive cytoplasm; and (iv) fibrous gliosis: lesions composed of densely packed mature astrocytes. The astrocyte lysis and progenitor recruitment stages dominated in clinically acute cases (within 2 months after the last recurrence). Findings common to both stages were the loss of AQP4, a decreased number of oligodendrocytes, the selective loss of myelin-associated glycoprotein and active demyelination with phagocytic macrophages. The infiltration of polymorphonuclear cells and T cells (CD4-dominant) and the deposition of activated complement (C9neo), which reflects the membrane attack complex, a hallmark of acute NMOSD lesions, were selectively observed in the astrocyte lysis stage (98.4% in astrocyte lysis, 1.6% in progenitor recruitment, and 0% in protoplasmic gliosis and fibrous gliosis). Although most of the protoplasmic gliosis and fibrous gliosis lesions were accompanied by inactive demyelinated lesions with a low amount of inflammatory cell infiltration, the deposition of complement degradation product (C3d) was observed in all four stages, even in fibrous gliosis lesions, suggesting the past or chronic occurrence of complement activation, which is a useful finding to distinguish chronic lesions in NMOSD from those in multiple sclerosis. Our staging of astrocytopathy is expected to be useful for understanding the unique temporal pathology of AQP4-IgG+NMOSD.

A case of primary ovarian signet-ring cell carcinoma treated with S-1/CDDP therapy.

BACKGROUND: Primary ovarian signet-ring cell carcinoma is extremely rare, with only five recent case reports. Almost all reported cases of ovarian signet-ring cell carcinoma have been treated with TC therapy and none have reported regarding the use of S-1/CDDP therapy. We report a case of primary ovarian signet-ring cell carcinoma treated postoperatively with S-1/CDDP therapy. CASE PRESENTATION: We describe a 55-year-old woman diagnosed with stage IB primary ovarian signet-ring cell carcinoma that was treated with S-1/CDDP therapy. Preoperative transvaginal ultrasonography and contrast-enhanced computed tomography (CT) revealed a solid tumor measuring 10 cm in diameter in the pelvis. The tumor marker levels were as follows: CA125, 41.6 U/mL; CA19-9, < 2.0 U/mL; and CEA, 2.2 ng/mL. Ovarian cancer was suspected, and total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. The left ovary was enlarged to greater than fist-sized, and there was a small amount of clear yellow ascites. Histological examination of the left ovary led to the diagnosis of signet-ring cell carcinoma. Histological examination of the right ovary also showed the presence of a signet-ring cell carcinoma. After surgery, upper and lower gastrointestinal endoscopy and positron-emission tomography-CT were performed to search for a possible primary lesion, but none was found. The patient was diagnosed with primary ovarian signet-ring cell carcinoma with FIGO Stage IB (PT1b, NX, M0). As postoperative adjuvant chemotherapy, S-1/CDDP therapy (S-1120 mg/day/body × 14 days, CDDP 50 mg/m2 day 8, q 21 days) was administered for six cycles. There was no recurrence 27 months after the initial treatment. CONCLUSIONS: We considered S-1/CDDP therapy was effective for primary ovarian signet-ring cell carcinoma. This is the first case report of primary ovarian signet-ring cell carcinoma treated with S-1/CDDP therapy in the world.

Angiomyofibroblastoma of the vulva diagnosed preoperatively: A case report.

A 50-year-old woman (gravida 2, para 2) first noticed a small nodule in the right labium majus 2 years prior to the initial visit to the Hachinohe Red Cross Hospital (Hachinohe, Japan), which had gradually increased in size. On physical examination, a well-circumscribed, elastic, firm, goose egg-sized, subcutaneous mass protruding from the right labium majus was identified. On magnetic resonance imaging (MRI), the lesion was hypointense on T1-weighted images and was well-circumscribed, strongly enhanced and homogeneous on gadolinium-enhanced images, measuring 7.5×4 cm. The same tumor had measured 2.6 cm on an MRI performed 6 years earlier. Based on the clinical course and imaging findings, angiomyofibroblastoma was diagnosed and surgical resection of the tumor was performed. The tumor was well-circumscribed and highly vascular. The intraoperative blood loss was 70 ml. Histopathologically, the tumor cells were concentrated around blood vessels, were spindle-shaped to oval with mild atypia, and were positive for vimentin, desmin, neural cell adhesion molecule (N-CAM), CD-34, estrogen receptor and progesterone receptor, and negative for S-100. Based on these findings, the diagnosis of angiomyofibroblastoma was confirmed. Angiomyofibroblastoma is a benign mesenchymal tumor that occurs in the female external genitalia. Differentiation of this tumor from aggressive angiomyxoma, a fast-growing infiltrative malignancy that occurs in the same region, may be challenging. The diagnosis of angiomyofibroblastoma is usually based on the histopathological findings of the resected specimen. The present case is of value, as the angiomyofibroblastoma was successfully diagnosed preoperatively based on the clinical course and imaging findings.

Clinical and pathological characteristics of homogeneous and nonhomogeneous tissue of in-stent restenosis visualized by optical coherence tomography.

BACKGROUND: Although it is known that in-stent restenosis (ISR) patterns appear homogeneous or nonhomogeneous by optical coherence tomography (OCT), interpretations of the ISR inflammatory response, of the OCT image, and its pathological implications are unclear. The aim of this study was to use OCT to characterize ISR and its inflammatory index in patients after coronary stenting. METHODS: OCT was performed at follow-up in 100 angiographic ISR lesions. ISR lesions were divided into two groups: (a) homogeneous (n=48) and (b) nonhomogeneous (n=52) image groups. We assessed the ISR images produced by OCT for tissue heterogeneity and neo-intimal hyperplasia using the normalized standard deviation of OCT signal-intensity (OCT-NSD) observed in neo-intimal hyperplasia tissue. In some patients with a nonhomogeneous OCT image, we collected pathological tissue. RESULTS: The prevalence of drug-eluting stents was 48% in the nonhomogeneous group and 29% in the homogeneous group (P=0.05). The OCT-NSD value in the nonhomogeneous group (0.223±0.019) was significantly higher than that in the homogeneous group (0.203±0.025; P<0.0001). Pathological tissue showed fibrin thrombi with infiltrating macrophage in 12 cases of nonhomogeneous ISR. The area under the receiver operating characteristic curve for the prediction of a nonhomogeneous image was 0.73 for OCT-NSD (95% confidence interval: 0.62-0.83: P<0.0001). The odds ratio for the prediction of a nonhomogeneous image was 3.47 (95% confidence interval: 1.18-10.2: P=0.02) for smoking by logistic regression analysis. CONCLUSION: Nonhomogeneous ISR visualized by OCT showed a high OCT-NSD value, which was a useful predictor for nonhomogeneous images. Moreover, the nonhomogeneous ISR image visualized by OCT may show chronic inflammation and fibrin thrombi.

Multiple carcinoid tumors of the rectum: report of two cases suggesting the origin of carcinoid tumors.

Two cases of multiple carcinoid tumors of the rectum with numerous micronests of carcinoid tumors are reported. The patients were 51- and 58-year-old males. Many carcinoid tumors and numerous carcinoid micronests were found in the resected rectum; the total number of carcinoid tumors, groups of micronests, and solitary micronests was 69 in the first case and 62 in the second case. The micronests, consisting of a few to many endocrine cells, were observed in the lamina propria, muscularis mucosa, and/or submucosa. Micronests increased in number, gathered and formed carcinoid tumors, which were up to 8 mm in diameter. It was found that a nest of the carcinoid tumors in the lamina propria showed continuity with the endocrine cells of a crypt in the different carcinoid tumors in both cases. The carcinoid tumor and micronest infiltrated the nerves and ganglions in the muscularis mucosa and submucosa. Nests of the carcinoid tumors and micronests were surrounded by S-100-positive cells. Lymph node metastases of the carcinoid tumor were found in both cases. Rectal carcinoid tumors may originate from endocrine cells of the crypts, and multiple carcinoid tumors may occur heterogeneously.

Parathyroid carcinoma with anaplastic feature: association of a p53 gene mutation with anaplastic transformation.

Parathyroid carcinoma is a rare neoplasm that accounts for only 1-3% of cases of primary hyperparathyroidism. Parathyroid carcinoma is a well-differentiated tumor that is sometimes difficult to differentiate histopathologically from its benign counterpart, parathyroid adenoma. The molecular mechanism of parathyroid carcinogenesis remains unknown, and investigators have reported that abnormalities of the p53 gene do not play a significant role in parathyroid carcinogenesis, unlike in other human malignancies. The present report describes parathyroid carcinoma with anaplastic transformation of differentiated parathyroid carcinoma in a patient with primary hyperparathyroidism. Nuclear accumulation of p53 protein was found in anaplastic carcinoma cells but not in differentiated carcinoma cells. Polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing showed that anaplastic carcinoma cells carried a missense mutation at codon 248 (CGG to CAG) of the p53 gene, while the remaining differentiated carcinoma cells had the wild-type p53 gene. These findings suggest that the p53 gene mutation is associated with anaplastic transformation of parathyroid carcinoma.

Primitive neuroectodermal tumor of the breast: immunohistochemistry and fluorescence in situ hybridization.

A case of primitive neuroectodermal tumor (PNET) that developed as a breast lump in a 47-year-old Japanese woman is reported. After fine-needle aspiration (FNA) cytology, a mastectomy was performed. The surgical specimen was a well-circumscribed tumor, 21 x 18 x 18 mm, localized in the breast. The tumor cells were small and round with scant cytoplasm, and proliferated in sheets or solid nests. No intraductal carcinoma component was present. The tumor cells were immunohistochemically positive for neural cell adhesion molecule (CD56), neuron-specific enolase and synaptophysin, and they showed membranous immunoreactivity for the MIC2 protein (CD99). Fluorescence in situ hybridization (FISH) indicated a rearrangement of the EWS region on chromosome 22, which is highly specific for Ewing's sarcoma and PNET, which are referred to as the Ewing's sarcoma family of tumors (EFT). No other lesions suggestive of the primary site of this tumor, such as bone, soft tissue, or other organs were detected. The patient has been disease free for 6 months after surgery followed by chemoradiation therapy. FISH is extremely useful for accurate diagnosis of EFT, especially in cases of unusual locations.

[A case of recurrent GIST of the esophagus which completely responded to imatinib mesilate].

Middle and lower esophagectomy was performed in a 68-year-old man in 1997 for the local recurrence of esophageal submucosal tumor after enucleation of the tumor. We subsequently performed partial hepatectomy for multiple liver metastases in 2001. The tumor was first diagnosed as GIST in the histological examinations of the liver metastases. However, 12 months after the hepatectomy, further recurrent lesions were found in multiple lymph nodes, in the remnant liver, and in the pancreas, as well as in the subcutaneous tissue. The lesions were initially considered unresectable, and we thus started an internal use of Glivec (400 mg/day) since July 2004. Within 2 months,all detected recurrent lesions changed into liquid forms,and the size of the subcutaneous tumor was also remarkably reduced. Accumulation of FDG was not seen on FDG-PET examination, suggesting the complete response of the tumor to Glivec. We still continue internal use of Glivec, and new recurrent lesions have not been detected up to now. Furthermore, the sizes of the liquid-regenerated lesions are gradually reducing.

Overexpression of laminin-5 gamma2 chain in clear cell carcinoma of the ovary.

One of the characteristic microscopic features of ovarian clear cell carcinoma (CCC) is the densely hyaline basement membrane material expanding the stroma. The biological significance of this material, however, has remained unclear. Recent studies have shown that laminin-5 (LN-5), a major component of the epithelial basement membrane, plays a more active role in cell migration or tumor invasion. In the present study, 20 CCCs and 5 borderline clear cell tumors were examined for LN-5 expression immunohistochemically, using an antibody against LN-5 gamma2 chain. All of the 20 CCCs showed a focal or diffuse immunoreactivity with the LN-5 gamma2 chain in the tumor stroma; whereas, borderline clear cell tumors rarely showed a stromal immunoreactivity. Cytoplasmic accumulation of the LN-5 gamma2 chain was far less common than stromal accumulation, suggesting an accelerated secretion in CCC. In vitro, CCC cell lines showed a significant increase in cell migration over excessive LN-5, and the migration was blocked by an antibody against integrin alpha3. These results indicate that an interaction between CCC cells and extracellularly accumulated LN-5 is responsible for cell migration and the subsequent stromal invasion of CCC.

Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary.

Clear cell tumors of the ovary are frequently associated with ovarian endometriosis. Clinicopathologically, it has been suggested that clear cell tumors develop from endometriosis, but there has been little molecular evidence supporting this speculation. Microarray analysis revealed recently that hepatocyte nuclear factor-1beta (HNF-1beta) was significantly upregulated in clear cell carcinoma of the ovary. In the present study, we examined 30 clear cell tumors (26 malignant, three borderline, and one benign) and 40 endometriotic cysts to clarify if differentiation into the clear cell lineage already begins in ovarian endometriosis. All of the 30 clear cell tumors, including borderline and benign ones, showed immunohistochemical expression of HNF-1beta in the nucleus, while other types of ovarian epithelial tumors (endometrioid, serous, mucinous, and Brenner tumors) rarely expressed it. Among 30 clear cell tumors, 17 (56%) cases were associated with endometriosis, and endometriotic epithelium was identified in 12 cases. In nine of the 12 cases, distinct nuclear immunostaining for HNF-1beta was detected in the endometriotic epithelium, as well as in the clear cell tumor. HNF-1beta expression was observed either in atypical endometriosis (four cases), or in endometriosis of a reactive nature (five cases). Furthermore, 16 of 40 (40%) endometriotic cysts without a neoplasm also expressed HNF-1beta, and the expression was almost exclusively observed in the epithelium showing inflammatory atypia. Our results indicate that HNF-1beta is an excellent molecular marker for ovarian clear cell tumors, including benign, borderline and malignant lesions. Early differentiation into the clear cell lineage takes place in ovarian endometriosis, not only in atypical endometriosis, but also in endometriosis with degenerative and regenerative changes, and this is probably responsible for the frequent occurrence of clear cell carcinoma in ovarian endometriosis.

KIT expression in normal and neoplastic renal tissues: immunohistochemical and molecular genetic analysis.

Renal chromophobe cell carcinomas (ChCC) and oncocytomas express KIT. This character seems to reflect their common histogenesis from distal nephrons. In the normal kidney, however, the expression and localization of KIT are unclear. KIT expression in angiomyolipoma and congenital mesoblastic nephroma (CMN), is still controversial. c-kit mutations are reportedly rare in ChCC, but there is little information in other renal neoplasms, and no reported data on mutations of platelet-derived growth factor receptor (PDGFR). In order to address these issues the authors examined five ChCC, five oncocytomas, seven papillary cell carcinomas, two collecting duct carcinomas, 12 angiomyolipomas, and three CMN, as well as 10 normal renal tissues. In the normal kidney KIT was specifically expressed in the distal nephrons. Nine of 12 (75%) angiomyolipomas contained scattered KIT-positive cells, whereas all three CMN were completely negative for KIT. The presence of KIT-positive cells in angiomyolipomas was likely to correspond to that of melanocytic marker-positive cells, which mainly showed epithelioid morphology. Polymerase chain reaction-single-strand conformation polymorphism showed no evidence of mutations of c-kit or PDGFR in any of the tumors examined.

Small cell neuroendocrine carcinomas of the uterine cervix: a histological, immunohistochemical, and molecular genetic study.

Small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. Although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. In this study, the authors tentatively defined small cell neuroendocrine carcinoma (SCNEC) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin A immunoreactivity, and synaptophysin immunoreactivity. We found 10 cases fulfilling these requirements. Five of the 10 tumors were composed mainly of small ("oat") cells and 5 of mainly larger "intermediate" cells. The majority of both subtypes showed an insular pattern. Three of the 10 SCNECs were pure, whereas the other seven were mixed with adenocarcinoma and/or squamous cell carcinoma or cervical intraepithelial neoplasia. In addition to the definitional markers noted earlier, the tumors were immunoreactive for serotonin (6 cases), somatostatin, gastrin, glucagon, and pancreatic polypeptide. No tumors were immunoreactive for cytokeratin 20. Human papillomavirus (HPV)-18 was detected in all of the pure tumors and both the SCNEC and adenocarcinomatous components in four of the mixed tumors. No other types of HPV were detected. The tumors showed a relatively low frequency of loss of heterozygosity for representative tumor suppressor gene sites; p53 mutations were found in only one case.

Synovial sarcoma of the thyroid. Report of a case with aspiration cytology findings and gene analysis.

BACKGROUND: Synovial sarcoma, generally known as a soft tissue tumor, can also occur in the head and neck region, including the thyroid gland. Cytologic findings are important to differentiate the tumor from other types of neoplasms arising in the thyroid gland. CASE: A 60-year-old man complained of hoarseness. A palpable neck tumor was detected, and a computed tomography scan showed a thyroid tumor accompanied by destruction of the thyroid and cricoid cartilage. The results of a preoperative fine needle aspiration biopsy showed numerous spindle cells with pale cytoplasm and oval nuclei with fine, granular chromatin, all of which suggested a medullary carcinoma. The extirpated thyroid tissue weighed approximately 120 g, and a grayish white, elastic, solid tumor (6.8 x 6.5 cm) was present in the left lobe. Histologically, fasciculation of spindle cells that had proliferated solidly and densely was observed. Also, the expression of a chimera gene, SYT-SSX, was detected in the tumor tissue. CONCLUSION: Synovial sarcoma of the thyroid is extremely rare, and its diagnosis by fine needle aspiration biopsy is generally considered very difficult. The detailed cytologic findings observed here might be helpful with the differential diagnosis of thyroid neoplasms.