Invasive cribriform carcinoma of the breast detected incidentally on computed tomography: A case report.

Invasive cribriform carcinoma is a rare type of invasive breast carcinoma, and a few cases have been reported. Its features are a cribriform pattern resembling the histological structures of cribriform ductal carcinoma in situ and an excellent prognosis. However, the extent of progress for intraductal extension must be carefully evaluated.

Sclerosing mucoepidermoid carcinoma of the salivary glands: report of three cases with special concern to the counterpart accompanied by eosinophilia.

Sclerosing mucoepidermoid carcinoma (SMC) is described as a "sclerosing variant" of mucoepidermoid carcinoma, and it is characterized by dense fibrosis and sclerosis of the stroma. SMC with eosinophilia (SMCE) is another and more rare subtype characterized by eosinophilia in addition to the sclerotic stroma common to SMC. However, unlike SMC, SMCE is not listed in the current 4th edition of WHO classification. Here, we describe three cases: one SMC in the parotid gland, one SMCE in the submandibular gland and one SMCE in the minor salivary gland of the oral cavity. The patients included a 71-year-old Japanese male, a 74-year-old Japanese female, and an 81-year-old Japanese female. They each complained of mass formation and underwent surgical resection. Histologically, the tumors mainly consisted of squamous cells with scarce keratinization that formed irregular large and small nests along with cystic structures containing mucous cells against the background of sclerotic stroma. One oral SMCE showed fine nesting and trabecular invasion. The two SMCEs included dense aggregates of eosinophils as well as more prominent lymphoid infiltration. Fluorescence in situ hybridization for MAML2 confirmed split signals in SMC, but not in SMCE.

[Two Cases of Synchronous Double Primary Prostate Cancer Accompanying Bone Metastasis and Colon Cancer].

We report two cases of synchronous double primary cancers, which were composed of prostate cancer accompanied by bone metastasis and colon cancer, within only five months of each other. The first was a 77-year-old man whose ECOG PS was 0. He was referred to our hospital in March 2020 because abdominal CT scan, which was performed at a clinic for the purpose of close examination of poor control of diabetes, showed wall thickening of the sigmoid colon. A further examination revealed prostate cancer accompanied by metastatic bone cancer and sigmoid colon cancer. Laparoscopic sigmoid colectomy was performed in April. Currently, six months after the surgery, both the prostate cancer and its accompanying metastatic bone cancer are well controlled by hormonal therapy. The second case was an 86-year-old man with an ECOG PS of 3 who was brought to our hospital by ambulance in August, 2020 because of fever and abdominal pain. A close examination revealed cecal cancer accompanying acute appendicitis. Prostate cancer accompanied by metastatic bone cancer was also diagnosed. Laparoscopic ileocecal resection was performed in the same month, but, unfortunately, the patient had repeated aspiration pneumonia and he finally passed away 43 days after surgery. We discuss the treatment strategy for colorectal cancer with synchronous or metachronous prostate cancer, which has been increasing in recent years, and include epidemiological considerations.

A case of "ETV6-FISH-negative" secretory carcinoma of the parotid gland: immunohistochemical study.

Secretory carcinoma of the salivary glands is a relatively new disease concept, and is characterized by "morphological resemblance to mammary secretory carcinoma and ETV6-NTRK3 gene fusion." Herein we describe a confusing case and briefly discuss practical diagnostic problems. The patient was a 71-year-old Japanese man who had a tumor consistent with secretory carcinoma at the microscopic and immunohistochemical levels. Immunohistochemically, EMA and S100 protein were noted to be positive along with various cytokeratins as well as mammaglobin and pSTAT5. Moreover, vimentin was focally positive. Smooth muscle actin, p63, p40, and androgen receptor were negative. However, a search using fluorescence in situ hybridization did not reveal a definite split signal for the ETV6 gene. It is presumed that confirming the diagnosis of secretory carcinoma without genetic retrieval will be accepted as a diagnostic method, and we hope that worldwide general recognition may earlier reach "gradual acceptance."

Chronic Inflammatory Demyelinating Polyneuropathy With Concurrent Membranous Nephropathy: An Anti-paranode and Podocyte Protein Antibody Study and Literature Survey.

Background: Several case reports have described the concurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN). The presence of autoantibodies against podocyte antigens phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) in MN suggests an autoimmune mechanism. Some CIDP patients also harbor autoantibodies against paranodal proteins such as neurofascin 155 (NF155) and contactin-1 (CNTN1). We investigated the relationship between CIDP and MN by assaying autoantibodies against paranodal and podocyte antigens in a CIDP patient with MN, and by a literature survey on the clinical features of CIDP with MN. Methods: Anti-CNTN1 and NF155 antibodies were measured by flow cytometry using HEK293 cell lines stably expressing human CNTN1 or NF155. Binding capacity of antibodies was validated by immunostaining mouse teased sciatic nerve fibers. Anti-PLA2R antibodies were measured by enzyme-linked sorbent assay and anti-THSD7A antibodies by indirect immunofluorescence assay. Clinical features between 14 CIDP with MN cases including two with anti-CNTN1 antibodies and 20 anti-CNTN1 antibody-positive CIDP cases were compared. Results: A patient whose ages was in the late 70 s complained of progressive weakness and superficial and deep sensory impairment in four extremities over 6 months. Nerve conduction studies showed prominent demyelination patterns. The patient presented with nephrotic syndrome. Renal biopsy disclosed basement membrane thickening with local subepithelial projections and glomerular deposits of IgG4, compatible with MN. Autoantibody assays revealed the presence of IgG4 and IgG1 anti-CNTN1 antibodies, but an absence of anti-NF155, anti-PLA2R, and anti-THSD7A antibodies. The patient's serum stained paranodes of teased sciatic nerves. CIDP with MN and anti-CNTN1 antibody-positive CIDP commonly showed male preponderance, relatively higher age of onset, acute to subacute onset in 35-50% of cases, distal dominant sensorimotor neuropathy, proprioceptive impairment leading to sensory ataxia, and very high cerebrospinal fluid protein levels. However, 11 of 13 CIDP patients with MN had a favorable response to mono- or combined immunotherapies whereas anti-CNTN1 antibody-positive CIDP was frequently refractory to corticosteroids and intravenous immunoglobulin administration. Conclusion: CIDP with MN and anti-CNTN1 antibody-positive CIDP show considerable overlap but are not identical. CIDP with MN is probably heterogeneous and some cases harbor anti-CNTN1 antibodies.

NUT carcinoma of the nasal cavity that responded to a chemotherapy regimen for Ewing's sarcoma family of tumors: a case report.

BACKGROUND: Nuclear protein in testis (NUT) carcinoma (NC) is a rare epithelial malignancy characterized by rearrangement of the NUT gene on chromosome 15. If NC is not suspected, it is often diagnosed as other malignancies. We present the case of NC of the nasal cavity that responded to a chemotherapy regimen for Ewing's sarcoma family of tumors (ESFT). CASE PRESENTATION: A 49-year-old male presented with epistaxis and pain in the left eye. The patient had a tumor in the left nasal cavity at initial visit and it was biopsied. Firstly, the man was diagnosed with ESFT based on a histopathological examination. The tumor markedly responded to standard cytotoxic chemotherapy for ESFT with distant metastasis. After the start of therapy, a chromosomal analysis revealed an atypical translocation in ESFT and additional immunostaining was positive for anti-NUT antibody. Ultimately, the patient was definitively diagnosed with NC. He received multidisciplinary therapy and symptoms were temporarily relieved. However, he died 9 months after the diagnosis of NC. CONCLUSIONS: When a pathologically undifferentiated tumor is evident along the midline of the body, NC must be included in the differential diagnosis, and immunohistochemical staining or genetic testing/chromosomal analysis needs to be performed.

Ependyma-Lined Canal with Surrounding Neuroglial Tissues in Lumbosacral Lipomatous Malformations: Relationship with Retained Medullary Cord.

BACKGROUND: An ependyma-lined canal with surrounding neuroglial tissues can be present in lumbosacral lipomatous malformations; however, the precise embryological significance is still unclear. METHOD: Six out of 50 patients with lipomatous malformations had ependymal structures. We retrospectively analyzed the clinical, neuroradiological, and histological findings of these patients to demonstrate the relationship with the embryological background of the retained medullary cord (RMC), which normally regresses, but was retained here because of late arrest of secondary neurulation. RESULTS: Five (13.9%) of 36 patients with filar and caudal types and 1 of 3 lipomyelomeningoceles had ependymal structures, while none with dorsal and transitional types had these tissues. Histologically, the ependymal structures surrounded by neuroglial tissue and containing various amounts of adipose tissue bear a striking resemblance to the ependymal structures in RMC. CONCLUSION: The 13.9% incidence of association between the ependymal structures and filar and caudal types is thought to be because of second ary neurulation failure with the same embryological background as that of RMC. Dorsal and transitional types, resulting from primary neurulation failure, therefore, did not have ependymal structures.

Neurosurgical pathology of limited dorsal myeloschisis.

PURPOSE: The term limited dorsal myeloschisis (LDM) was used by Pang et al. (2010) to describe a distinct clinicopathological entity. LDMs are characterized by two invariable features: a focal-closed neural tube defect and a fibroneural stalk that links the skin lesion to the underlying spinal cord. METHODS: We retrospectively analyzed the neurosurgical pathologic findings of four LDM patients. RESULTS: Case 1 had a saccular skin lesion with nonterminal abortive myelocystocele at T11-12. Cases 2, 3, and 4 had a non-saccular (flat) skin lesion in the lumbosacral region. The morphologic features of the lesion in case 2 were those of meningocele manque. Cases 3 and 4 had accompanying non-LDM anomalies, caudal-type lipoma and type II split-cord malformation with neurenteric cyst, respectively. At preoperative diagnosis of the LDM stalk, magnetic resonance imaging, including 3D heavily T2-weighted image was useful; however, minute findings were often missed in the complicated cases 3 and 4. All patients had a favorable outcome following untethering of the stalk from the cord. The central histopathological feature of the LDM stalk is neuroglial tissue in the fibrocollagenous band; however, the stalk in cases 2 and 4 did not have glial fibrillary acidic protein-immunopositive neuroglial tissues. CONCLUSIONS: Therefore, the diagnosis of LDM should be made based on comprehensive evaluation of histologic and clinical findings.

Epstein-Barr virus-positive diffuse large B-cell lymphoma following acute myeloid leukemia: a common clonal origin indicated by chromosomal translocation t(3;4)(p25;q21).

Secondary non-Hodgkin lymphoma following acute myeloid leukemia (AML) is extremely rare. We here describe a unique case involving a patient who developed Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) during complete remission (CR) of AML. A 75-year-old Japanese man was initially diagnosed with AML with maturation (FAB M2), bearing chromosomal translocation t(3,4)(p25;q21). After intensive chemotherapy, bone marrow aspiration revealed normal karyotype, and he achieved CR. Six years and 4 months later, he was still in CR from AML, but developed DLBCL presenting in the terminal ileum. Cytogenetic analysis of the DLBCL cells showed the same translocation as the previous AML. The rearrangements of the immunoglobulin heavy chain genes of the two malignancies were examined using polymerase chain reaction amplification, and the rearrangement patterns were found to differ from each other. Our data thus suggest that, in the present case, the AML and DLBCL arose from a common progenitor cell, as indicated by the clonal abnormality t(3,4)(p25;q21), and that different immunoglobulin heavy chain gene rearrangements occurred during each course of clonal evolution.

[A Case of Locally Advanced Gastric Cancer after Neoadjuvant Chemotherapy].

A 60s male was admitted to our hospital because of appetite loss and nausea. After examination, he was diagnosed with type 3 advanced gastric cancer in the antrum. Abdominal computed tomography showed gastric cancer invasion to the left liver lobe. We initiated neoadjuvant chemotherapy using S-1 plus CDDP after laparoscopic gastrojejunostomy. S-1 was orally administered for 3 weeks followed by a 2-week drug-free period. CDDP was administered intravenously on day 8 of each course. After 5 courses of chemotherapy, the gastric cancer was reduced in size. We therefore performed total gastrectomy with D2-affiliated left liver resection. S-1 plus CDDP is expected to improve outcomes in unresectable or locally advanced gastric cancer.

Unilateral gynecomastia and pseudoangiomatous stromal hyperplasia in neurofibromatosis: case report and review of the literature.

In this article, we describe unilateral gynecomastia and pseudoangiomatous stromal hyperplasia (PASH) in a case of type-1 neurofibromatosis (NF-1). It is important to distinguish PASH from fibroadenoma clinically, and from true blood capillaries and angiosarcoma histologically. In the present case, giant multinucleated cells lined the pseudovascular spaces, which was markedly different from that of conventional breast PASH. The origin of PASH has been reported to be either the fibroblast or the myofibroblast phenotype and may be affected by endocrine signaling because many cases have been reported in premenopausal women, and cases are often estrogen (ER) and progesterone receptor (PR) positive. However, previous reports have identified PASH in NF-1 in juvenile males only, and the cases were negative for α-SMA, ER and PR. The cause and prognosis of PASH in NF-1 may be distinguished from that of conventional PASH, and mast cells, histiocytes and CD54 may play roles.

Prostate cancer cells increase androgen sensitivity by increase in nuclear androgen receptor and androgen receptor coactivators; a possible mechanism of hormone-resistance of prostate cancer cells.

Although androgen-hypersensitivity is one of the possible pathways of hormone-resistance in prostate cancer, the mechanisms of androgen-hypersensitivity are still largely unknown. Using androgen-hypersensitive prostate cancer cells LN-TR2, established from androgen-sensitive LNCaP cells by the long term treatment with tumor necrosis factor alpha, we explored the mechanisms of androgen-hypersensitivity in prostate cancer cells which may thus play a role in hormone-resistance. We examined the androgen receptor (AR) DNA sequence and the expression levels of AR and 8 AR cofactors in LNCaP and LN-TR2 cells. As a result, no novel mutation was developed in AR DNA in LN-TR2 cells. We observed higher expressions of nuclear AR upon androgen-treatment and 2 AR coactivators, ARA55 and TIF2, in LN-TR2 compared to LNCaP cells. An overexpression of ARA55 or TIF2 enhanced androgen-induced AR transcriptional activity in LNCaP cell. In the presence of those AR coactivators, AR activity was observed even at low concentrations of androgen. In 2 of 6 patients, the expression level of ARA55 was higher in cancer cells in hormone-resistant tumor than those in hormone-sensitive tumor. Taken together, our results suggest that prostate cancer cells change androgen-sensitivity by an overexpression of nuclear AR and AR coactivators, thus, resulting in transition from androgen-dependent to androgen-independent prostate cancer cells. An increase in nuclear AR and AR coactivators may cause androgen-hypersensitivity of prostate cancer cells and thus play a role in hormone-resistance, at least in some patients with prostate cancer.

Association of verrucous carcinoma and inverted papilloma in the sinonasal tract.

It is well known that inverted papilloma (IP) is sometimes associated with malignancies; however, the association of IP with verrucous carcinoma (VC) is extremely rare. We herein report a case of IP in the nasal cavity with VC in the maxillary sinus. A 73-year-old Japanese woman presented with a 3-month history of right-sided nasal obstruction and repetitive epistaxis. A biopsy of the mass was performed and the pathological result proved to be IP. Computed tomography and magnetic resonance imaging revealed a moderately enhanced soft-tissue lesion filling the right nasal cavity and a ring-enhanced expansive lesion in the maxillary sinus. Under a tentative diagnosis of IP of the nasal cavity with maxillary empyema, she underwent right medial maxillectomy via a lateral rhinotomy approach, and a histopathological diagnosis of IP in the nasal cavity with VC in the maxillary sinus was obtained. Her postoperative clinical course was uneventful. She is currently free from symptoms, and there is no evidence of recurrence 5 months after surgery. The pathology, clinical manifestation, and treatment of VC associated with IP are reviewed from literature.

YB-1 is important for an early stage embryonic development: neural tube formation and cell proliferation.

The eukaryotic Y-box-binding protein-1 (YB-1) is involved in the transcriptional and translational control of many biological processes, including cell proliferation. In clinical studies, the cellular level of YB-1 closely correlates with tumor growth and prognosis. To understand the role of YB-1 in vivo, especially in the developmental process, we generated YB-1 knock-out mice, which are embryonic lethal and exhibit exencephaly associated with abnormal patterns of cell proliferation within the neuroepithelium. beta-Actin expression and F-actin formation were reduced in the YB-1 null embryo and YB-1(-/-) mouse embryonic fibroblasts, suggesting that the neural tube defect is caused by abnormal cell morphology and actin assembly within the neuroepithelium. Fibroblasts derived from YB-1(-/-) embryos demonstrated reduced growth and cell density. A colony formation assay showed that YB-1(-/-) mouse embryonic fibroblasts failed to undergo morphological transformation and remained contact-inhibited in culture. These results demonstrate that YB-1 is involved in early mouse development, including neural tube closure and cell proliferation.

Correlation between numeric gadolinium-enhanced dynamic MRI ratios and prognostic factors and histologic type of breast carcinoma.

OBJECTIVE: The purpose of this study was to assess the usefulness of numeric ratios from dynamic contrast-enhanced MRI in predicting histologic type of breast carcinoma and three histologic prognostic factors for invasive ductal carcinoma. MATERIALS AND METHODS: A total of 104 patients with breast carcinoma were included in the study. Dynamic contrast-enhanced MR images were obtained every 30 seconds during the first 4.5 minutes after administration of contrast material, and peripheral contrast enhancement ratio and central contrast enhancement ratio were calculated in the early phase (1 minute after contract injection) and in the delayed phase (4 minutes after injection). Four contrast enhancement ratios were used for quantitative analysis of the following numeric ratios: early peripheral/early central, delayed peripheral/delayed central, delayed peripheral/early peripheral, and delayed central/early central. The four ratios were compared with histologic type. For invasive ductal carcinoma, the ratios were then compared with modified Scarff-Bloom-Richardson histologic grade, microvessel density, and fibrotic focus. RESULTS: Mucinous carcinoma had significantly higher mean early peripheral/early central and delayed central/early central ratios than other types of tumors (p< 0.0001). For invasive ductal carcinoma, the mean early peripheral/early central ratio was significantly lower for modified Scarff-Bloom-Richardson grade 1 tumors than for grades 2 and 3 tumors (p < 0.0001). Early peripheral/early central ratio had a significant correlation with the ratio of peripheral to central mean microvessel density (p < 0.0001). There was also a significant difference in early peripheral/early central ratio (p < 0.0001) between tumors with a fibrotic focus and those without a fibrotic focus. CONCLUSION: Numeric ratios obtained on gadolinium-enhanced dynamic MRI of the breast may be useful in predicting histologic type of breast carcinoma and three histologic prognostic factors for invasive ductal carcinoma: modified Scarff-Bloom-Richardson grade, microvessel density, and fibrotic focus.

Valvular and supravalvular aortic stenosis in heterozygous familial hypercholesterolemia, a case report.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by a high level of LDL-cholesterol and frequent coronary atherosclerosis. We studied a 64 year old woman with heterozygous (hetero) FH, who showed symptoms of chest pain and dyspnea with no other coronary risk factors than post-menopause and hypercholesterolemia. Although her coronary symptoms didn't reveal significant stenosis on coronary angiography, she had severe aortic valvular and supravalvular stenosis at the ascending aorta, which qualified her for aortic valve replacement. Moreover, a coronary flow study revealed functional ischemia with a reduction of the coronary flow reserve. We report a case of valvular and supravalvular aortic stenosis corrected by aortic valve replacement, a rare complication of hetero FH.