Brain metastasis in a patient with BRCA2-mutated treatment-related neuroendocrine prostate carcinoma and long-term response to radiotherapy and Olaparib: A case report and literature review.

BACKGROUND: A new subtype of prostate cancer called treatment-related neuroendocrine prostate carcinoma (t-NEPC) was added to the revised World Health Organization classification of prostate cancer in 2022. t-NEPC cases are increasing, and there is no established standard treatment. METHODS: A 49-year-old male patient was referred to our department for dysuria. A rectal examination and a prostate biopsy revealed stony hardness and prostate adenocarcinoma, respectively. Imaging studies confirmed the presence of multiple bone and lymph node metastases. The patient was started on upfront treatment with androgen deprivation therapy and an androgen receptor signaling inhibitor, which resulted in a significant (>90%) decrease in prostate-specific antigen (PSA) levels. The patient experienced postrenal failure 6 months later, attributable to local disease progression. Concurrently, there was an elevation in neuron-specific enolase (NSE) levels and an enlargement of pelvic lymph node metastases, without PSA progression. RESULTS: Biopsy specimen for cancer genome profiling revealed deletion of BRCA 2 and PTEN, AR amplification, and the presence of the TMPRSS2-ERG fusion gene. Based on increased NSE and BRCA2 mutations, a diagnosis of t-NEPC with BRCA2 mutation was eventually made. The patient received docetaxel chemotherapy and pelvic radiotherapy. Subsequently, he was treated with olaparib. His NSE levels decreased, and he achieved a complete response (CR). However, 18 months following the olaparib administration, brain metastases appeared despite the absence of pelvic tumor relapse, and the patient's PSA levels remained low. Consequently, the patient underwent resection of the brain metastases using gamma knife and whole-brain radiotherapy but died approximately 3 months later. CONCLUSION SUBSECTIONS: Platinum-based chemotherapy is often administered for the treatment of t-NEPC, but there are few reports on the effectiveness of olaparib in patients with BRCA2 mutations. In a literature review, this case demonstrated the longest duration of effectiveness with olaparib alone without platinum-based chemotherapy. Additionally, the occurrence of relatively rare, fatal brain metastases in prostate cancer after a long period of CR suggests the necessity of regular brain imaging examinations.

Exophytic cavernous hemangioma arising from the right ventricle: Report of a rare case.

Cardiac hemangioma is relatively rare, accounting for approximately 1-3% of all primary heart tumors. This benign tumor may be an incidental lesion, but can also cause arrhythmias, pericardial effusion, congestive heart failure or outflow obstruction. We report a rare case with exophytic cardiac hemangioma arising from the right ventricle. Echocardiography showed an approximately 40 mm round protruding mass on the anterior wall of the right ventricle. Cardiovascular magnetic resonance demonstrated isointense and hyperintense signals on T1- and T2-weighted images, respectively. These imaging studies suggested a pericardial cyst. Perioperative findings indicated a globular, exophytic mass, vascular in nature, arising from the right ventricle. The lesion was resected directly, and the space left by defect in the right ventricular wall was covered with a bovine pericardial patch. Cardiac hemangiomas are generally endoluminal tumors, but we must keep in mind that the differential diagnoses include various pericardial lesions by medical images.

Tectal Low-Grade Glioma with H3 K27M Mutation.

BACKGROUND: In the revised World Health Organization 2016 classification of central nervous system tumors, "diffuse midline glioma, H3 K27M-mutant" has been added as a new diagnostic entity. However, some confusion exists concerning this diagnostic entity because H3 K27M-mutant diffuse midline glioma is diagnosed with grade IV regardless of morphologic phenotype. Furthermore, the significance of H3 K27M mutation in tumors that aren't typical "diffuse midline glioma, H3 K27M-mutant," such as those with an unusual location and nontypical histology, remains unclear. CASE DESCRIPTION: To elucidate further such unusual tumors, we describe here a rare case of pediatric low-grade glioma located in the tectum, which was morphologically a pilocytic astrocytoma (PA) with genetically H3 K27M mutation but no microvascular proliferation, necrosis, mitoses, or other genetic alterations, insofar as we were able to observe. At the latest follow-up, 28 months after surgery, radiotherapy, and chemotherapy, the patient was found to be free from any neurologic deficits and MRI demonstrated that the tumor was stable without tumor regrowth. This case might be identified as "diffuse midline glioma, H3 K27M-mutant", grade IV, when applying only the current World Health Organization 2016 classification. In addition, we discuss the morphologically benign gliomas harboring the H3 K27M mutation based on the literature. CONCLUSIONS: We describe here a rare case and present a short literature review of circumscribed/nondiffuse gliomas, particularly in PA with H3 K27M mutation. However, the significance of H3 K27M mutation for PA remains unclear, so further studies and clinical data are needed to elucidate the biology and optimal treatment of such tumors.

Idiopathic myenteric ganglionitis as a cause of death in a young male patient with sudden abdominal pain: an autopsy case report.

BACKGROUND: Myenteric ganglionitis is a disorder that causes intestinal motor dysfunction. It may be caused due to neoplastic, central nervous system, or systemic infectious disorders. However, some cases are considered to be idiopathic in origin. CASE PRESENTATION: A 33-year-old man was admitted to the hospital with sudden severe abdominal pain accompanied by watery diarrhea. Computed tomography imaging revealed edema of the entire small intestinal wall without ischemic changes. Detailed examination could not be performed for identifying the cause of abdominal pain because of the patient's worsened general condition, and he died 7 days after onset. The autopsy results confirmed the cause of the patient's severe abdominal pain as an idiopathic myenteric ganglionitis. CONCLUSION: Some patients with idiopathic myenteric ganglionitis might die without a definitive diagnosis during their lifetime because of the rarity of this disease. When encountering severe intestinal motility abnormalities of unknown cause, physicians should consider idiopathic myenteric ganglionitis when choosing therapy.

Papillary glioblastoma exhibiting a neuroradiological cyst with a mural nodule: A case report.

RATIONALE: Glioblastomas are malignant, infiltrating gliomas classified as grade IV by the World Health Organization. Genetically, most glioblastomas do not exhibit the isocitrate dehydrogenase (IDH) 1/2 gene mutation and rarely harbor the 1p/19q co-deletion. Neuroradiologically, glioblastomas rarely form a cyst with a mural nodule lesion. PATIENT CONCERNS: In this study, a 78-year-old woman, with speech difficulty and forgetfulness, had a cystic tumor with a mural nodule in the right frontoparietal lobe. Therefore, partial tumor resection was performed. DIAGNOSIS: Histopathology of the tumor, a glioblastoma, exhibited pseudopapillary features with non-hyalinized capillary cores and rich mini-gemistocytic cells. Genetic analysis of the tumor revealed co-deletion of 1p36/19q13, with wild-type IDH. INTERVENTIONS: The patient underwent a combination of postoperative radiotherapy and temozolomide chemotherapy before leaving the hospital. After discharge, she was treated by 20 courses of temozolomide chemotherapy. OUTCOMES: The patient is free from tumor recurrence 23 months after the operation. LESSONS: We present a unique case of glioblastoma that exhibited novel neuroradiological, histopathological, and genetic features with a favorable prognosis for the patient. Therefore, a compilation of similar cases with clinicopathological and genetic analyses to characterize this unique glioblastoma is critical. Clinical evidence will help develop effective therapeutic approaches to improve prognosis in patients with glioblastoma.

A symptomatic large subependymoma with neuroradiological features mimicking a high-grade glioma: A case report.

A subependymoma is a benign primary brain tumor classified as a World Health Organization grade I tumor; it is asymptomatic in most cases. We present the case of a 66-year-old Japanese man with a complaint of recurrent vomiting that led to the discovery of a large mass with hemorrhage, peritumoral edema, and a midline shift in the posterior horn of the right lateral ventricle. The patient was pathologically diagnosed with subependymoma after undergoing total tumor resection; a year after the surgery, he was free from tumor recurrence. Although symptomatic subependymomas are rare, they tend to show hemorrhage with peritumoral edema on neuroradiological tests and tend to be confused with high-grade brain tumors. In the present case, we highlight the importance of the appropriate diagnosis for subependymomas showing neuroradiological features that mimic high-grade gliomas. This diagnosis will help in providing suitable treatment for subependymomas.

Uterine corpus tumor with neuroectodermal differentiation and frequent ganglion-like cells in a postmenopausal woman.

•Uterine neuroectodermal tumors (NETs) are uncommon malignant neoplasm with poor prognosis.•Ganglion-like cells with fibrillary background as major component of uterine NETs are extremely rare.•We present a patient affected by uterine NET with frequent ganglion-like cells, resembling ganglioneuroblastoma.•This case report is important to define the pathogenesis and establish better treatments for neuroectodermal tumors.

Overexpression of Activation-Induced Cytidine Deaminase in MTX- and Age-Related Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders of the Head and Neck.

Recent research has shown that activation-induced cytidine deaminase (AID) triggers somatic hypermutation and recombination, in turn contributing to lymphomagenesis. Such aberrant AID expression is seen in B-cell leukemia/lymphomas, including Burkitt lymphoma which is associated with c-myc translocation. Moreover, Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) increases genomic instability through early growth transcription response-1 (Egr-1) mediated upregulation of AID in B-cell lymphoma. However, few clinicopathological studies have focused on AID expression in lymphoproliferative disorders (LPDs). Therefore, we conducted an immunohistochemical study to investigate the relationship between AID and LMP-1 expression in LPDs (MTX-/Age-related EBV-associated), including diffuse large B-cell lymphomas (DLBCLs). More intense AID expression was detected in LPDs (89.5%) than in DLBCLs (20.0%), and the expression of LMP-1 and EBER was more intense in LPDs (68.4% and 94.7%) than in DLBCLs (10.0% and 20.0%). Furthermore, stronger Egr-1 expression was found in MTX/Age-EBV-LPDs (83.3%) than in DLBCLs (30.0%). AID expression was significantly constitutively overexpressed in LPDs as compared with DLBCLs. These results suggest that increased AID expression in LPDs may be one of the processes involved in lymphomagenesis, thereby further increasing the survival of genetically destabilized B-cells. AID expression may be a useful indicator for differentiation between LPDs and DLBCLs.

Successful pregnancy in a case of bladder and ovary endometriosis following cystoscopy-assisted laparoscopic resection.

A 34-year-old, gravida 0 para 0 Japanese woman visited a regional hospital complaining of dysmenorrhea, hematuria during menstruation, and right inguinal pain. She had a history of dysmenorrhea and three prior rounds of in vitro fertilization with embryo transfer, which were all with transfers of cryopreserved-thawed single embryos in natural cycles, resulting in no pregnancy. An ultrasound revealed a large 2 × 1-cm nodule between the bladder and the anterior wall of the uterus and a 3-cm cystic lesion in the right adnexal area. A combined cystoscopic and laparoscopic resection of the bladder endometriosis and cystectomy of the right endometrioma were carried out. A single ultrasound-guided transfer of a cryopreserved-thawed embryo in the cleavage stage was performed 4 months postoperatively, which resulted in an uncomplicated pregnancy. The combined, single procedure was minimally invasive and eradicated the lesions that may have caused the infertility.

Renal abscess involving mucormycosis by immunohistochemical detection in a patient with acute lymphocytic leukemia: a case report and literature review.

A 14-year-old girl with acute lymphocytic leukemia complained of right flank pain and fever. As her fever was prolonged, she underwent renal biopsy and was diagnosed with mucormycosis. We performed right nephrectomy, and subsequent pathological examination of her tissue specimen also detected mucormycosis. Here, we report a rare case of renal mucormycotic abscess.

Differentiation and apoptosis in pilomatrixoma.

We carried out a histopathologic study of pilomatrixoma, a benign skin tumor, and also examined apoptosis and hair differentiation with the aim to understand the presence of amorphous debris and cyst formation in the tumor. Among 16 cases of pilomatrixoma examined, 11 were at the early regressive stage and 5 were at the late regressive stage according to the classification by Kaddu et al. In the former cases, tumor nests were basically composed of basophilic, transitional, and shadow cells. Cyst formation was evident in all cases and squamoid epithelium was observed in 4 cases at the early regressive stage. Amorphous debris was found in all cases including those at the late regressive stage. Immunohistochemical analysis revealed positive reaction products for ß-catenin and Lef-1 in basophilic and transitional cells, although their distribution differed. Immunoreactivity for ß-catenin was observed in the lower transitional cells, whereas immunoreactivity for Lef-1 was also evident in the upper transitional cells. Positive reactions for hair keratins were found in the cytoplasm of transitional and shadow cells, but not in the amorphous debris. Examination by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method revealed positive reactions in transitional and some shadow cells. These results suggest that in pilomatrixoma, production of hair keratin and induction of apoptosis may occur at the same time, and that unlike the normal hair follicle irregular expression of ß-catenin and Lef-1 results in the appearance of amorphous debris and cyst formation.

The significance of podoplanin expression in human inflamed gingiva.

Podoplanin, a transmembrane glycoprotein, has been considered to be expressed specifically by lymphatic endothelial cells. However, recent studies have shown that the protein is expressed in a variety of normal as well as neoplastic tissues, and that its expression might be related to cell migration and invasion. In this study, we examined podoplanin expression in inflamed gingival tissues using an immunohistochemical method. Positive immunoreactivity for podoplanin was found in the cell membrane and cytoplasm of basal cells of oral gingival epithelium when severe inflammatory cell infiltration was present in the connective tissue just under the epithelium. When inflammatory changes were weak or absent, little or no reactivity for podoplanin in the basal cells was observed. Positive reactivity for podoplanin was also detected in basal cell extensions. Surprisingly, strong immunoreactivity for podoplanin was observed in all layers of oral sulcular and junctional epithelia associated with severe inflammatory reaction in the connective tissue. These findings suggest that increased expression of podoplanin in gingival epithelium is related to the progression of chronic periodontitis.

Supplemental utility of nested PCR for the pathological diagnosis of disseminated trichosporonosis.

Disseminated trichosporonosis is known to be a severe opportunistic mycosis and has a high mortality rate. In autopsy cases, it is often difficult to diagnose as trichosporonosis because the causative Trichosporon species are pathologically similar to other fungi, especially the Candida species. Immunohistochemical analysis is essential for the differential diagnosis, but an antibody to Trichosporon is not available commercially. In the present study, we investigated the supplemental utility of nested polymerase chain reaction (PCR) for the pathological diagnosis of trichosporonosis from formalin-fixed and paraffin-embedded tissues. Total DNA was purified from 30 major organs in three autopsy cases, and Trichosporon DNA was specifically amplified by nested PCR using three sets of primers. Of 22 organs in which Grocott's stain was positive for fungal infection, 170- and 259-bp PCR products were detected in 20 (91%) and 12 (55%) organs, respectively. In short-term fixation (about 1 day), these bands were highly detected in ten (100%) and nine (90%) organs, whereas the detection efficiency tended to decrease after long-term fixation and decalcification. No PCR product of 412 bp was detected in any organs. These findings suggest that nested PCR from short-term-fixed tissues is useful for supportive pathological diagnosis of disseminated trichosporonosis.

Vascular endothelial growth factor and dendritic cells in human squamous cell carcinoma of the oral cavity.

Dendritic cells (DCs) play an important role in the host immune defense against tumors, and there is an inverse correlation between DC density and the expression of vascular endothelial growth factor (VEGF). However, the relationship between VEGF expression in tumors and infiltration of CD1a+ or CD83+ DCs, which express the VEGF receptor (VEGFR), remains unclear. Therefore, in vivo and in vitro studies were conducted to investigate the relationship between VEGF expression and DC subsets in oral squamous cell carcinomas (OSCCs). Strong VEGF expression was detected in cancer tissues from patients with regional lymph node metastasis (PN+ cases). In these tissues, the VEGF expression correlated inversely with the number of CD1a + DCs, but positively with the number of CD83+ DCs. Large amounts of VEGF were secreted by OSCCs cell lines, and their culture supernatants significantly inhibited the production of differentiated CD1a+ DCs from peripheral blood mononuclear cells (PBMCs), whereas differentiated CD83+ DCs were increased. VEGFR-1 and -2 were detected in a few PBMCs and CD1a+ DCs. Furthermore, CD1a mRNA disappeared when recombinant human VEGF165 (rhVEGF165) was added to CD1a+ DCs, while CD83 mRNA increased. These results suggest that, in OSCCs, secreted VEGF might promote escape from tumor immunity by inhibiting the differentiation of CD1a + DCs from progenitor cells and increasing the levels of dysfunctional CD83+ DCs.

Expression of hard alpha-keratins in pilomatrixoma, craniopharyngioma, and calcifying odontogenic cyst.

To examine the properties of shadow and ghost cells, 3 kinds of antibodies were raised against human hair proteins and their immunoreactivity was examined in tumors expressing those cells: pilomatrixoma, 14 cases; craniopharyngioma, 17 cases; and calcifying odontogenic cyst (COC), 14 cases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses demonstrated that 2 polyclonal antibodies, PA-HP1 and PA-HP 2, reacted strongly with type I acidic and type II neutral/basic hard alpha-keratins. The other monoclonal antibody, MA-HP1, reacted with type II neutral/basic hard alpha-keratins. Immunohistochemical examination revealed that all 3 antibodies reacted only with the hair shaft in sections of normal skin and dermoid cyst. In all pilomatrixoma cases, 3 antibodies reacted with the cytoplasm of transitional and shadow cells but not with that of basophilic cells. Positive reactions were found only in shadow cells of all 13 adamantinomatous craniopharyngiomas. In all COCs, the antibodies reacted only with ghost cells, not with other epithelial components. Immunoreactivity for phosphothreonine, detected in hard alpha-keratins, also was found in transitional, shadow, and ghost cells. The appearance of shadow or ghost cells might represent differentiation into hair in these 3 kinds of tumors.