Prognostic usefulness of a modified risk model for solitary fibrous tumor that includes the Ki-67 labeling index.

BACKGROUND: Predicting the prognosis of patients with solitary fibrous tumor (SFT) is often difficult. The prognostic risk models developed by Demicco et al. are now the standard for evaluating the risk of SFT metastasis in the current World Health Organization classification of soft tissue and bone tumors. METHODS: In this study, we examined the prognostic usefulness of a modified version of the Demicco risk models that replaces the mitotic count with the Ki-67 labeling index. We compared the three-variable and four-variable Demicco risk models with our modified risk models using Kaplan-Meier curves based on data for 43 patients with SFT. RESULTS: We found a significant difference in metastasis-free survival when patients were classified into low-risk and intermediate/high-risk groups using the three-variable (P = 0.022) and four-variable (P = 0.046) Demicco models. There was also a significant difference in metastasis-free survival between the low-risk and intermediate/high-risk groups when the modified three-variable (P = 0.006) and four-variable (P = 0.022) models were used. CONCLUSION: Modified risk models that include the Ki-67 labeling index are effective for prediction of the prognosis in patients with SFT.

Identification of characteristic subepithelial surface granulomatosis in immune-related adverse event-associated enterocolitis.

Immune checkpoint inhibitors (ICIs) have provided an additional treatment option for various types of human cancers. However, ICIs often induce various immune-related adverse events (irAEs). Enterocolitis is a major irAE with poorly understood histopathological characteristics. In this study, we retrospectively investigated the histopathology of colon tissue samples from 17 patients treated with ICIs. There were two major histological patterns of colitis: an ulcerative colitis-like pattern and a graft vs host disease-like pattern. Although these two patterns of colitis were mutually exclusive, both patterns often showed a characteristic that we call "subepithelial surface granulomatosis" (SSG), which has not been reported in other types of colitis. SSG was found even in colon tissue without symptoms or endoscopic findings of colitis. Given the increasing reports of sarcoid reaction or exacerbation of tuberculosis after treatment with ICIs, granuloma formation could be a histological hallmark of systemic immune activation by ICIs. Although statistical significance was not obtained, probably because of the small sample size, SSG may be a surrogate biomarker of systemic anticancer immune activation. We propose that a prospective study with larger sample size be performed.

Image analysis is an excellent tool for quantifying Ki-67 to predict the prognosis of gastrointestinal stromal tumor patients.

We investigated the quantification of Ki-67 staining using digital image analysis (IA) as a complementary prognostic factor to the modified National Institutes of Health (NIH) classification in patients with gastrointestinal stromal tumor (GIST). We examined 92 patients, focusing on the correlation between age, sex, primary tumor site, tumor size, predominant histologic type, mitotic index, modified NIH classification (low/intermediate vs high), Ki-67 quantitation, and recurrence-free survival (RFS). We compared two IA processes for whole slide imaging (WSI) and manually captured image (MCI) methods. A Ki-67 quantitation cutoff was determined by receiver operator characteristics curve analysis. In the survival analysis, the high-risk group of a modified NIH classification, a mitotic count >5 per 20 high-powered fields, and Ki-67 cutoffs of ≥6% and ≥8% obtained by IA of the WSI and MCI methods, respectively, had an adverse impact on RFS. On multivariate analysis, each Ki-67 quantitation method strongly predicted prognosis, more strongly than the modified NIH classification. In addition, Ki-67 quantitation using IA of the MCI method could stratify low or intermediate risk and high risk GIST patients. Thus, IA is an excellent tool for quantifying Ki-67 to predict the prognosis of GIST patients, and this semiautomated approach may be preferable for patient care.

Diagnostic utility of automated SureFISH (Dako Omnis) in the diagnosis of musculoskeletal translocation-related sarcomas.

Fluorescence in situ hybridization (FISH) is an essential tool for genetic diagnosis in daily pathological work. Almost full automation of FISH can be achieved with the recently released automated SureFISH platform (Dako Omnis, Agilent Technologies, Santa Clara, CA, USA). Its utility has been reported in HER2 amplification of breast and gastric carcinoma and ALK-rearranged lung cancer. Here, we examined the utility of automated SureFISH for the identification of rearrangement signals in translocation-related sarcomas (TRSs), including 11 EWSR1-rearranged and 10 synovial sarcoma cases, compared with non-automated conventional FISH using the same specimens. The percentages of EWSR1 or SS18 split signals were higher in automated SureFISH than in conventional FISH in 13 of the 21 cases. On the other hand, 8 of the 21 cases showed the same or lower percentage of split signals in automated SureFISH. Both FISH approaches detected EWSR1 and SS18 split signals in more than 10% of tumor cells in all cases. The strongest advantage of automated SureFISH is its ability to reduce running time without sacrificing quality. Other advantages include improved signal sharpness with oligo probes and reduced ecological toxicity by avoiding formamide use. Automated SureFISH is an excellent tool for the genetic diagnosis of TRSs and contributes to their rapid definitive diagnosis.

[Bone Flap Resorption after Cranioplasty in Pediatric Patients:Report of 2 Cases].

Aseptic bone flap resorption, a rare complication after cranioplasty following decompressive craniectomy, is more likely to develop in children. We experienced two cases of aseptic bone flap resorption and identified potential pathophysiological mechanisms through histological findings. In the first case, an 11-year-old girl underwent decompressive craniectomy due to brain swelling with contusion. An autologous bone flap was cryopreserved for four months. Twenty-five months after cranioplasty with autologous bone flap, aseptic bone flap resorption was observed, and cranioplasty was performed with ceramic bone. Most of the histological findings in this case showed mature osseous tissue, while some showed osteoclasts and new bone formation due to endochondral ossification. In the second case, a 10-year-old girl underwent frontal craniectomy and removal of contusional hematoma. Fourteen months after cranioplasty with autologous bone flap, aseptic bone flap resorption was observed, and cranioplasty was performed with ceramic bone paste. The progression of bone flap resorption was not recognized for 12 months. In these cases, new bone formation was not necessarily linked to pathological bone flap resorption. It is supposed that the balance between bone destruction and new bone formation was disrupted by unknown factors.

Sec6/8 regulates Bcl-2 and Mcl-1, but not Bcl-xl, in malignant peripheral nerve sheath tumor cells.

Sec6 and Sec8, which are components of the exocyst complex, has been concerned with various roles independent of its role in secretion, such as cell migration, invadopodia formation, cytokinesis, glucose uptake, and neural development. Given the vital roles of the exocyst complex in cellular and developmental processes, the disruption of its function may be closely related to various diseases such as cancer, diabetes, and neuronal disorders. Malignant peripheral nerve sheath tumors (MPNSTs) have high malignant potential and poor prognosis because of aggressive progression and metastasis. To date, no chemotherapeutic agents have been validated for MPNSTs treatment because how MPNSTs are resistant to chemotherapeutic agents remains unknown. This study demonstrates that combination of doxorubicin and sorafenib induces apoptosis in MPNST cells through downregulation of B cell lymphoma protein 2 (Bcl-2), Bcl-2-related protein long form of Bcl-x (Bcl-xl), and myeloid cell leukemia 1 (Mcl-1). Moreover, both Sec6 and Sec8 levels decreased after treatment with doxorubicin and sorafenib and were found to be associated with Bcl-2 and Mcl-1 expressions, but not Bcl-xl. Although Sec8 was found to be involved in the regulation of both Bcl-2 and Mcl-1 at the mRNA level, Sec6 regulated Bcl-2 at the mRNA level and the binding affinity of F-box and WD repeat domain containing 7 and Mcl-1, thereby controlling Mcl-1 at the protein level. Bcl-2 or Mcl-1 mRNA suppression by Sec6 or Sec8 depletion resulted in significant changes in nuclear factor-kappa B, cAMP response element, and p53 transcriptional activity. These results suggest that Sec6 and Sec8 are therapeutic target molecules in MPNST.

Solid type primary intraosseous squamous cell carcinoma in the maxilla: report of a new case.

BACKGROUND: Primary intraosseous squamous cell carcinoma is a rare jaw bone tumor defined as squamous cell carcinoma arising within the jaw, having no initial connection with the oral mucosa and developing from residual odontogenic epithelium or from an odontogenic cyst or tumor. Solid type of this tumor arising in the maxilla is an even rarer presentation, because the majorities derive from cystic lesions and are found in the posterior mandible. CASE PRESENTATION: A 36-year-old Japanese man was referred to our clinic with a complaint of pain around the anterior maxillary region on the right side. Intraoral examination identified a firm, non-fluctuant mass with no ulceration in the vestibular region of teeth #11-13. Incisional biopsy was performed, leading to histological diagnosis of moderately differentiated squamous cell carcinoma. Contrast-enhanced computed tomography revealed a destructive tumor with no cystic lesion, >50 mm in diameter. There was no evidence of metastatic disease on chest radiography, upper gastric endoscopy or positron emission tomography. Based on these findings, solid type primary intraosseous squamous cell carcinoma was diagnosed. The patient underwent tumor ablative surgery. The surgical defect was reconstructed using a partially double-folded free radial forearm flap and prefabricated denture-based surgical obturator. The postoperative course was quite good. Neither recurrence nor metastasis had been found as of 3 years and 1 month postoperatively. CONCLUSION: To the best of our knowledge, the present case represents only the 10th case of solid type primary intraosseous squamous cell carcinoma arising in the maxilla to be reported.

Case Report: A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis.

Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for >3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed TP53 Q192X mutation, whereas SMAD4 S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in TP53. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the TP53 gene might have occurred during the differentiation of the founder clone into NEC, while a SMAD4 mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.

The Nuss technique for Jeune asphyxiating thoracic dystrophy repair in siblings.

Jeune syndrome, or asphyxiating thoracic dysplasia, is an autosomal recessive osteochondrodysplasia. Four forms of Jeune syndrome have been proposed: lethal, severe, mild, and latent. In the severe form, respiratory failure leads to death in early infancy. We present 2 cases of a mild variant of Jeune syndrome in a 14-year-old girl and her 9-year-old brother, who were referred to us because of characteristic concave deformities of bilateral middle-lower chest walls without cardiopulmonary distress or renal failure. In addition, both showed short statue (-2.1 and -2.5 SD), progressive retinal dystrophy, and metaphyseal dysplasia (cone-shaped metaphysis and metacarpal brachydactyly). The chest wall deformity was treated at the age of 9 years in the sister and at the age of 7 years in the brother. According to the Nuss procedure, 2 bent bars were inserted into the thoracic cavity from each lateral intercostal space at the midaxillary line and pulled out over the lower end of the sternum. The ends of inserted bars were fixed to soft tissue over the sternum with nonabsorbable sutures. Conjoined costal cartilage around the sternum restricts the number of bars that can be positioned. A single bar for deformity of each side could not achieve complete reconstruction, but the patients and their parents were satisfied with the results cosmetically.

Snapping elbow with congenital radial head dislocation: case report.

An 11-year-old boy with congenital radial head dislocation experienced painful snapping of his left elbow upon movement. He had no previous history of trauma. A plain radiograph of his left elbow showed anterior dislocation of the radial head and flexion deformity of the hypoplastic radial neck. Arthroscopy showed that the snapping of the elbow occurred between the annular ligament and the dislocated radial head during elbow flexion and extension. After the annular ligament was released, the snapping immediately disappeared. Five years after the surgery, the patient has no pain or snapping upon elbow movement.

Occult carcinoma confirmed to be a diffuse sclerosing variant of papillary thyroid carcinoma with unusual immunohistochemical features: A pitfall of clinicopathological diagnosis.

Immunocytochemistry in a 78-year-old man diagnosed as having systemic metastatic cancer of unknown primary origin revealed atypical cells positive for napsin A and TTF-1, suggesting adenocarcinoma of the lung. However, there was no evidence of a primary lesion in the lung on positron emission tomography/computed tomography or at autopsy. Meanwhile, both the left and right thyroid lobes were firm and grayish white with marked fibrosis. Histology identified a diffuse sclerosing variant of papillary thyroid carcinoma that was positive for TTF-1 and napsin A but negative for PAX8. This disease entity is often misdiagnosed clinically as chronic thyroiditis. This is the first report of napsin A-positive and PAX8-negative thyroid carcinoma and highlights the pitfalls of clinicopathological diagnosis.

Occurrence of central polydactyly, syndactyly, and cleft hand in a single family: report of five hands in three cases.

Central polydactyly, syndactyly, and cleft hand are categorized separately in the International Federation of Societies for Surgery of the Hand classification. However, some investigators have proposed that these malformations should be classified into a single category: abnormal induction of finger rays. In this article, we report 5 hands with central polydactyly, syndactyly, and cleft hand in 3 patients from the same family and discuss the phenotypes in each hand.

De Quervain disease caused by abductor pollicis longus tenosynovitis: a report of three cases.

De Quervain disease is caused by a stenosing tenosynovitis in the first dorsal compartment, and the main aetiology is extensor pollicis brevis (EPB) tenosynovitis. We encountered three cases in which EPB tenosynovitis was absent and abductor pollicis longus (APL) tenosynovitis was confirmed during operation. In the treatment of de Quervain disease, APL tenosynovitis should be paid as much attention as EPB tenosynovitis.

Reconstruction methods after total pharyngolaryngoesophagectomy: free jejunal graft and venous-reconstructed gastric tube or gastric tube alone.

BACKGROUND/AIMS: The aim of this study is to assess the postoperative outcome of the two reconstruction methods using both a free jejunal graft and a venous-reconstructed gastric tube or a gastric tube alone after total pharyngolaryngoesophagectomy. METHODOLOGY: We reconstructed the pharyngoesophagus using both a free jejunal graft and a gastric tube in 5 cases (JG group), including 4 in whom the gastric vein was reconstructed, and using a gastric tube alone in 8 cases (G group). We compared the two groups in terms of postoperative complications, operation time, blood loss and length of postoperative hospital stay. RESULTS: In the JG group, jejunal graft necrosis occurred in a case, although 4 cases with gastric venous reconstruction had no postoperative problems. In the G group, although anastomotic trouble occurred in 3 cases, 7 patients were discharged from hospital with oral feeding. In the JG group, postoperative stay was shorter, but the operation time was longer, than those in the G group. CONCLUSIONS: Reconstruction using a free jejunal graft and a venous-reconstructed gastric tube is useful especially for patients with a long defect in the pharyngoesophagus. These 2 methods may be used according to the length of the pharyngoesophageal defect.

Meningioma mimicking an intraparenchymal cystic tumor.

Meningiomas rarely exhibit cystic lesions with mural nodules, and may be misdiagnosed as intraparenchymal cystic tumors. We herein present a 64-year-old woman with a cystic lesion and enhancing mural nodule in the left temporal lobe accompanied by peritumoral brain edema. Differential diagnoses included low-grade gliomas, hemangioblastoma, and cystic meningioma. Gross total resection of the tumor was achieved through a temporal surgical approach. Intraoperative findings showed that the tumor was an extraparenchymal tumor. The cyst was covered by an extraparenchymal thin membrane and the cystic fluid was yellowish in color. The final result of the pathological examination was microcystic meningioma, WHO grade I. Although intraparenchymal tumors, such as hemangioblastoma, ganglioglioma, pilocytic astrocytoma, and pleomorphic xanthoastrocytoma, commonly display this MRI pattern, meningioma needs to be included in the differential diagnosis.

Trichorhinophalangeal syndrome type II without the chromosome 8 deletion that resembled metachondromatosis.

We describe a 5-year-old girl with features resembling Trichorhinophalangeal syndrome, type I (sparse scalp hair, bushy eyebrows, bulbous nose, long philtrum, cone-shaped epiphyses, clinobrachydactyly, epiphyseal changes in the femoral head and short stature), and appendicular exostoses similar to trichorhinophalangeal syndrome, type II. However, despite physical resemblance to the trichorhinophalangeal syndrome variants, cytological analysis showed a structurally normal chromosome 8 and no mental deficiency was apparent. In addition, morphological congruities between multiple exostoses and metachondromatosis was indicated from radiographic findings.

Myoepithelioma of the upper lip.

Myoepithelioma is a rare form of salivary gland tumor composed entirely of myoepithelial cells. This tumor was formerly considered to be a subtype of pleomorphic adenoma; however, in the 1991 World Health Organization classification, it is listed as an independent entity. The most favorable site of occurrence of myoepithelioma is the parotid gland. Here, we report an extremely rare case of myoepithelioma of the upper lip. A 56-year-old woman presented with a painless mass on her upper lip. Magnetic resonance imaging revealed a 23 mm × 18 mm well-defined ovoid tumor. A benign minor salivary gland tumor was clinically suspected, and the patient underwent complete resection of the tumor under general anesthesia. The tumor was histopathologically diagnosed as a benign myoepithelioma of the minor salivary gland. Immunohistochemically, the tumor cells were positive for S-100 protein, AE1/AE3, CAM5.2, CK7, vimentin, and calponin, confirming the morphologic diagnosis of myoepithelioma. The patient's postoperative clinical course was uneventful, and satisfactory results were obtained both functionally and esthetically. To the best of our knowledge, this is the sixth case of myoepithelioma of the upper lip reported in English-language research.

Uterine epithelioid leiomyosarcoma with c-kit expression and YWHAE gene rearrangement: a case report of a diagnostic pitfall of uterine sarcoma.

BACKGROUND: Uterine sarcoma is a rare tumor that is often difficult to classify based on morphological and immunohistochemical analysis alone. Limited access to molecular biological analysis in routine practice would hinder making a definitive diagnosis. CASE PRESENTATION: In this report, we describe a case of a mesenchymal tumor arising from the uterine cervix in a 52-year-old woman. From microscopic morphology of the resected specimen, epithelioid leiomyosarcoma, high-grade endometrial stromal sarcoma, or uterine gastrointestinal stromal tumor (GIST) were considered as differential diagnoses. The immunophenotype of the tumor featured smooth muscle differentiation and hormone receptor expression. The cell membrane and cytoplasm were positive for c-kit, although no mutation was found in the c-kit or PDGFRA gene. Fluorescence in situ hybridization (FISH) analysis revealed a relatively low frequency of YWHAE rearrangement, whereas there were few NUTM2A and NUTM2B split signals. CONCLUSIONS: In this case, the tumor was not typical of any three of the differential diagnoses mentioned above. However, insufficient frequency of YWHAE, NUTM2A, and NUTM2B gene rearrangement and absence of mutation in both the c-kit and PDGFRA genes suggested that this tumor should be categorized as epithelioid leiomyosarcoma. This is an instructive case showing a potential diagnostic pitfall of uterine sarcoma. Comprehensive approaches including molecular biological techniques are required for definitive diagnosis.

Diagnostic utility of FOSB immunohistochemistry in pseudomyogenic hemangioendothelioma and its histological mimics.

BACKGROUND: Pseudomyogenic hemangioendothelioma (PHE) is an unusual vascular tumor of intermediate malignancy that rarely metastasizes and tends to arise in the lower limbs of young adults and children. Histologically, PHE shows fascicular proliferation of eosinophilic spindle cells and/or epithelioid cells showing "pseudomyogenic" morphology. Immunohistochemically, PHE is usually positive for vimentin, cytokeratin, CD31 and ERG. METHOD: We examined FOSB immunohistochemistry (IHC) in 27 cases consisting of 4 PHE and its histologic mimics including 6 epithelioid hemangioendotheliomas (EHE), 8 angiosarcomas (AS), 4 Kaposi sarcomas (KS) and 5 epithelioid sarcomas (ES). In addition, we performed IHC of CAMTA1 which has recently been established as a useful marker of EHE. We elucidated the diagnostic utility of FOSB IHC in the differential diagnosis of PHE and its histological mimics and also examined the usefulness of FOSB and CAMTA1 IHC combination in the differential diagnosis of the tumors. RESULTS: IHC revealed diffuse and strong FOSB expression in all PHE cases, while the other tumor types demonstrated limited, weak or no FOSB expression. All EHE cases exhibited diffuse and moderate to strong expression of CAMTA1. All tumor types except for EHE showed limited, weak or no CAMTA1 reactivity. CONCLUSIONS: Diffuse and strong FOSB expression was specific for PHE in the current series and FOSB IHC is an effective tool for differentiating between PHE and its histological mimics. Moreover, the combination of FOSB and CAMTA1 IHC is useful for distinguishing PHE from EHE.