Esophageal carcinosarcoma comprised of minimally invasive squamous cell carcinoma and undifferentiated pleomorphic sarcoma: A collision cancer?

Esophageal carcinosarcoma is a rare neoplasm with components of squamous cell carcinoma and sarcomatous spindle cell stroma. The latter may show overt mesenchymal differentiation but is thought to be derived from carcinoma cells in most cases. Here, we report a case of esophageal carcinosarcoma that appeared to be comprised of different origins of epithelial and mesenchymal tumor cells. The sarcomatous component formed an intralumial pedunculated large mass lesion that consisted of pleomorphic atypical histiocyte-like cells. The squamous epithelium exhibited features of mostly dysplasia with minor foci of microinvasive squamous cell carcinoma. The invasive carcinoma was apart from the sarcoma, and no transitions were observed between the epithelial and sarcomatous cells. Immunohistochemistry showed that the sarcoma cells did not express any lineage-specific markers, including those for epithelial cells and histiocytes, which lead to the diagnosis of undifferentiated pleomorphic sarcoma. Although cyclin D1 was overexpressed in the carcinoma cells, it was nearly negative in the sarcoma cells. These findings indicate that the tumor may be a collision carcinosarcoma. It is highly likely that the patient's history of heavy smoking and alcohol consumption were relevant to the pathogenesis, at least for the epithelial component, of the tumor.

Association of Epithelial Atypia With Recurrence After Surgical Excision in Conjunctival Papilloma.

PURPOSE: To investigate the association between recurrence of conjunctival papillomas and presence of atypical epithelial changes in patients undergoing surgical excision for conjunctival papilloma. METHODS: We retrospectively reviewed 1,195 ophthalmic pathology specimens from 2004 to 2014 at Ichikawa General Hospital. Pathologic specimens of 5 patients with a final diagnosis of "conjunctival papilloma" were stained with hematoxylin-eosin, Ki 67, p53, human papillomavirus (HPV) 16 and 18 antibodies. RESULTS: Of 1,195 patients, 5 patients (4 men, 1 woman; age range: 27∼57 years, mean age: 38.4 years) had a diagnosis of conjunctival papilloma, which constituted to 0.42% of the pathologic diagnosis made for the ophthalmology specimens. All specimens displayed multiple fronds of thickened conjunctival epithelium that enclosed cores of vascularized connective tissues. Three patients with recurrence after surgical excision demonstrated moderate to severe epithelial atypia, who also showed higher staining with Ki67 and p53 compared with patients with no recurrence. HPV16 and 18 antibodies staining did not appear to relate to recurrences. CONCLUSIONS: Conjunctival papillomas with higher positive staining for Ki67 and p53 seem to have a higher risk of recurrence even after complete surgical excision and necessitate careful follow-up.

Caruncular and Pericaruncular Sebaceous Gland Hyperplasia: A Report of 2 Cases and Literature Review.

PURPOSE: To report the clinical and histopathological features of two patients with caruncular and pericaruncular sebaceous gland hyperplasia (SGH) with a literature review. METHODS: We performed a retrospective pathology database search of 1195 ophthalmic specimens receiving the clinical diagnosis of SGH for caruncular/pericaruncular lesions during 2004 to 2014 at Tokyo Dental College, Ichikawa General Hospital. Paraffin sections were stained with hematoxylin and eosin. A retrospective patient record and literature review was also performed. RESULTS: Database search disclosed 2 male patients with SGH of 1195 specimens (0.15%). Pathological specimens revealed neither any cellular/nuclear atypia nor any mitotic figures and invasive features. No recurrences were observed in these 2 cases 12 to 18 months after excision. CONCLUSIONS: Caruncle and pericaruncular SGH is an uncommon lesion which needs careful histopathological evaluation for differentiation especially from caruncular neoplasias.

Monocyte Chemoattractant Protein-1 (MCP-1) as a Potential Therapeutic Target and a Noninvasive Biomarker of Liver Fibrosis Associated With Transient Myeloproliferative Disorder in Down Syndrome.

Liver fibrosis is one of the common complications of transient myeloproliferative disorder (TMD) in Down syndrome (DS), but the exact molecular pathogenesis is largely unknown. We herein report a neonate of DS with liver fibrosis associated with TMD, in which we performed the serial profibrogenic cytokines analyses. We found the active monocyte chemoattractant protein-1 expression in the affected liver tissue and also found that both serum and urinary monocyte chemoattractant protein-1 concentrations are noninvasive biomarkers of liver fibrosis. We also showed a prospective of the future anticytokine therapy with herbal medicine for the liver fibrosis associated with TMD in DS.

Cutoff Pepsinogen Level for Predicting Unintendedly Eradicated Cases of Helicobacter pylori Infection in Subjects with Seemingly Normal Pepsinogen Levels.

BACKGROUNDS/AIMS: In the ABC method, which is a method for risk stratification of gastric cancer using serum anti-Helicobacter pylori antibody and pepsinogen (PG) test, subjects with normal PG and seronegative for H. pylori are named as "Group A" and are regarded as having a low risk of gastric cancer. These "Group A" subjects include unintentionally eradicated cases at relatively high risk, and this study aimed to identify these subjects. METHODS: Of the 109 subjects, 76 were classified as uninfected Group A subjects with negative histologic H. pylori infection and no histologic and endoscopic atrophy, and 33 subjects were classified serologically as Group A after successful eradication, which are serologically equal to the unintendedly eradicated cases in Group A. The usefulness of measuring PG levels to detect post-eradication cases was validated by using a receiver operating characteristic (ROC) curve analysis. RESULTS: The area under the ROC curve for PGI level was 0.736 ± 0.06 (p < 0.01; cutoff value, 37.0 ng/mL; sensitivity, 77.6%; specificity, 72.7%), and that for the PGI/II ratio was 0.660 ± 0.06 (p < 0.01; cutoff value, 5.1; sensitivity, 84.2%; specificity, 43.4%). CONCLUSION: PGI levels of ≤37 ng/mL and PGI/II ratios of ≤5.1 effectively identified unintendedly eradicated cases in Group A.

Clear cell adenocarcinoma arising from adenomyotic cyst: A case report and literature review.

Ovaries are the primary sites of cancerous disease that is derived from endometriosis. Uterine cancer originating from endometriosis is very rare. The most frequent histological subtype of cancer derived from endometriosis is endometrioid adenocarcinoma, a subtype of clear cell carcinoma which is exceedingly rare. We report a case of a 40-year-old Japanese woman with a six year history of uterine leiomyoma. The patient was clinically and radiologically suspected to have degenerative uterine myoma with a possible malignant association and underwent a transabdominal total hysterectomy. Histopathological examination of the specimens revealed clear cell adenocarcinoma arising from the adenomyotic cyst. A literature review of clear cell adenocarcinomas arising from uterine adenomyotic cysts (cystic adenomyosis), emphasizes the clinically and radiologically important features of this very rare entity. Clear cell carcinoma association should be suspected in patients who are under follow-up for uterine myomas and present with cystic uterine changes with solid component on magnetic resonance imaging or computed tomography scans.

Fetal liver stromal cells support blast growth in transient abnormal myelopoiesis in Down syndrome through GM-CSF.

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome, which spontaneously resolves within several weeks or months after birth, may represent a very special form of leukemia arising in the fetal liver (FL). To explore the role of the fetal hematopoietic microenvironment in the pathogenesis of TAM, we examined the in vitro influences of stromal cells of human FL and fetal bone marrow (FBM) on the growth of TAM blasts. Both FL and FBM stromal cells expressed mesenchymal cell antigens (vimentin, α-smooth muscle actin, CD146, and nestin), being consistent with perivascular cells/mesenchymal stem cells that support hematopoietic stem cells. In addition, a small fraction of the FL stromal cells expressed an epithelial marker, cytokeratin 8, indicating that they could be cells in epithelial-mesenchymal transition (EMT). In the coculture system, stromal cells of the FL, but not FBM, potently supported the growth of TAM blast progenitors, mainly through humoral factors. High concentrations of hematopoietic growth factors were detected in culture supernatants of the FL stromal cells and a neutralizing antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) almost completely inhibited the growth-supportive activity of the culture supernatants. These results indicate that FL stromal cells with unique characteristics of EMT cells provide a pivotal hematopoietic microenvironment for TAM blasts and that GM-CSF produced by FL stromal cells may play an important role in the pathogenesis of TAM.

[Staging and evaluation of bone marrow involvement in lymphoma].

Staging of lymphoma is important for predicting the prognosis and deciding on the treatment strategy for each patient. The Ann Arbor classification and its Cotswolds revised version are widely used, and now comprise the standard staging system for lymphoma. Bone marrow involvement is one of the most important factors in the staging system. Pathological patterns of lymphoma cell infiltration in the marrow are categorized into the following types: 1) nodular/patchy, 2) paratrabecular, 3) interstitial, 4) diffuse, and 5) intrasinusoidal. The frequency and patterns of bone marrow involvement in association with the subtypes of lymphoma are reviewed. PET/CT analysis has become a powerful method for staging lymphoma, and may complement or substitute for bone marrow biopsy in some subtypes of lymphoma.

The hematopoietic microenvironment of the fetal liver and transient abnormal myelopoiesis associated with Down syndrome: A review.

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome is a distinct form of leukemia or preleukemia that mirrors the hematological features of acute megakaryoblastic leukemia. However, it typically resolves spontaneously in the early stages. TAM originates from fetal liver (FL) hematopoietic precursor cells and emerges due to somatic mutations in GATA1 in utero. In TAM, progenitor cells proliferate and differentiate into mature megakaryocytes and granulocytes. This process occurs both in vitro, aided by hematopoietic growth factors (HGFs) produced in the FL, and in vivo, particularly in specific anatomical sites like the FL and blood vessels. The FL's hematopoietic microenvironment plays a crucial role in TAM's pathogenesis and may contribute to its spontaneous regression. This review presents an overview of current knowledge regarding the unique features of TAM in relation to the FL hematopoietic microenvironment, focusing on the functions of HGFs and the pathological features of TAM.

An unfavorable and a successful pregnancy outcome during and after treatment of gamma heavy chain disease.

Gamma heavy chain disease (gHCD) is a rare B-cell lymphoproliferative disorder that mostly occurs after childbearing age. Here we report the first case of gHCD in a pregnant patient that was diagnosed in the second trimester, and another pregnancy in the same patient after initial treatment for gHCD. The former pregnancy ended in intrauterine fetal death, believed to be caused by insufficient maternal blood flow due to multiple placental infarcts. The latter pregnancy course was uneventful. Although we cannot rule out the possibility that the poor outcome of the former pregnancy was due to an unfortunate complication independent of gHCD, the courses of these pregnancies suggest that non-lymphomatous gamma heavy chain may have a significant impact on pregnancy and that its removal by treatment may improve outcomes.

[Epidural abscess in the spine extended from pulmonary zygomycosis during consolidation chemotherapy for acute lymphoblastic leukemia].

A 37-year-old woman with acute lymphoblastic leukemia developed fever and pneumonia during persistent neutropenia after consolidation chemotherapy. Pneumonia was rapidly followed by the formation of abscess in adjacent subcutaneous tissues, muscles and bones. She subsequently developed sudden onset of paraplegia and loss of all sensation below Th4. Epidural abscess was detected by MRI. Emergency drainage was performed, but the patient died 4 days after the operation. Rhizopus oryzae grew from culture of the epidural abscess. Since the incidence of zygomycosis appears to have increased over the recent years, clinicians should be aware of the possibility of zygomycosis in case of any infection that is resistant to antibiotics.

The in vitro effects of hepatoblastoma cells on the growth and differentiation of blasts in transient abnormal myelopoiesis associated with Down syndrome.

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome, which spontaneously resolves within several weeks or months after birth, may represent a special form of leukemia developing in the fetal liver (FL). To explore the role of hepatoblasts, one of the major constituents of the FL hematopoietic microenvironment, in the pathogenesis of TAM, we investigated the influence of a human hepatoblastoma cell line, HUH-6, on the in vitro growth and differentiation of TAM blasts. In a coculture system with membrane filters, which hinders cell-to-cell contact between TAM blasts and HUH-6 cells, the growth and megakaryocytic differentiation of TAM blast progenitors were increased in the presence of HUH-6 cells. The culture supernatant of HUH-6 cells contained hematopoietic growth factors, including stem cell factor (SCF) and thrombopoietin (TPO). The neutralizing antibody against SCF abrogated the growth-stimulating activity of the culture supernatant of HUH-6 cells, demonstrating that, among the growth factors produced by HUH-6 cells, SCF may be the major growth stimulator and that TPO may be involved in megakaryocytic differentiation, rather than growth, of TAM blasts. This suggests that hepatoblasts function in the regulation of the growth and differentiation of TAM blasts in the FL through the production of hematopoietic growth factors, including SCF and TPO, and are involved in the leukemogenesis of TAM.

CD8-positive T cells and CD204-positive M2-like macrophages predict postoperative prognosis of very high-risk prostate cancer.

To stratify the heterogeneity of prostate cancer (PCa) with seminal vesicle invasion (SVI) immunologically after radical prostatectomy focusing on the tumor microenvironment. We retrospectively reviewed the clinicopathological data of 71 PCa patients with SVI, which is known as a factor of very high-risk PCa. Preoperative clinical variables and postoperative pathological variables were evaluated as predictors of biochemical recurrence (BCR) with a multivariate logistic regression. Immune cell infiltration including the CD8-positive cell (CD8+ cell) and CD204-positive M2-like macrophage (CD204+ cell) was investigated by immunohistochemistry. The cumulative incidence and risk of BCR were assessed with a Kaplan-Meier analysis and competing risks regression. A higher CD8+ cell count in the SVI area significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). A lower CD204+ cell count in the SVI area also significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). Furthermore, the combination of the CD8+ and CD204+ cell infiltration ratio of the SVI area to the main tumor area was a significant factor for BCR in the patients with the PCa with SVI (p = 0.001). In PCa patients with SVI, the combination of CD8+ and CD204+ cell infiltration is useful to predict the prognosis.

Blasts in transient leukaemia in neonates with Down syndrome differentiate into basophil/mast-cell and megakaryocyte lineages in vitro in association with down-regulation of truncated form of GATA1.

Mutations of GATA1, leading to aberrant expression of a truncated form of GATA1 (called GATA1s), are present in transient leukaemia (TL) in neonates with Down syndrome. Using these molecular markers of TL, we investigated the growth and differentiation potential of TL blasts in the presence of hematopoietic growth factors (HGFs). Interleukin-3, stem cell factor and granulocyte-macrophage colony-stimulating factor potently stimulated the growth of TL blast progenitors and induced differentiation towards basophil/mast cell lineages, whereas thrombopoietin induced differentiation towards megakaryocytes. GATA1s was expressed in TL blasts in all five patients examined but was down-regulated during differentiation induced by these HGFs, while full-length GATA1 was not expressed throughout the culture. GATA1 mutations were detected in TL blasts in four patients, including one patient with two distinct mutations. The cells of this patient exhibited identical and only mutated sequences both before and after culture with HGFs, confirming the leukemic cell origin of these differentiated cells. Erythroid differentiation of TL blasts was not evident with any HGFs. These data indicate that TL blasts have the potential to grow and differentiate towards particular hematopoietic lineages in the presence of specific HGFs and that the down-regulation of GATA1s might be involved in blast cell differentiation.

[A case of advanced adenocarcinoma of the lung which maintained complete response for 5 years by treatment with gefitinib].

A 73-year-old woman smoker presented with dyspnea on exertion due to massive left pleural effusion. A CT scan after drainage of the pleural effusion demonstrated a nodule in the left lung, and cytology of the pleural effusion showed adenocarcinoma. We diagnosed advanced adenocarcinoma of the lung, and clinical stage IIIB. Chemotherapy with carboplatin and docetaxel was discontinued after the second course because of anorexia, and gefitinib was administered from October 2004. The lung nodule and pleural effusion had disappeared on CT by November 2004. A complete response continued for 5 years. We report a 5-year complete response in a case of advanced adenocarcinoma of the lung by treatment with gefitinib.

[A case of miliary tuberculosis showing acute respiratory distress syndrome in rheumatoid arthritis].

A 62-year-old man, treated with corticosteroids and immunosuppressants for rheumatoid arthritis, visited hospital with high fever and dyspnea on exertion. A CT scan of the chest demonstrated bilateral diffuse ground glass opacities. On the basis of the findings of the CT scan, he was initially given a diagnosis of interstitial pneumonia. He was then referred to our hospital and admitted to the intensive care unit (ICU), where because of progressive respiratory failure, he was put on mechanical ventilation. A bronchoscopy specimen after intubation turned out to be positive for acid-fast bacilli, which were confirmed to be mycobacterium tuberculosis by a polymerase chain reaction test. He was given a diagnosis of miliary tuberculosis complicated with acute respiratory distress syndrome (ARDS). He died of respiratory failure despite treatment with antituberculosis drugs. The autopsy revealed necrotizing epithelioid granulomas in both lungs, mediastinal lymph nodes, the liver, both kidneys, vertebrae and other organs. Diffuse alveolar damage was also found in both lungs. It is often difficult to detect disseminated nodules in the miliary tuberculosis with ARDS. Miliary tuberculosis should be suspected in patients in an immunosuppressant state with rheumatoid arthritis, and who have respiratory symptoms or fever of unknown origin.

Heterochronous Suture Line Recurrences in the Jejunal Pouch following Total Gastrectomy for Stage II Gastric Cancer: A Case Report and Literature Review.

We report the case of a 65-year-old male who developed heterochronous local recurrences of gastric cancer in the jejunal pouch (J-pouch) four times after total gastrectomy. He underwent total gastrectomy, J-pouch, and Roux-en-Y reconstruction for stage II gastric cancer in 2005. Four local recurrences appeared on the esophago-jejunal anastomosis, the suture line within the pouch, the esophago-jejunal anastomosis, and the anastomosis between the jejunum and Y-loop, which were resected by partial excision or endoscopic submucosal dissection. Suture line recurrence of gastric cancer is rare. The common features for each recurrence included the surgically negative resection margins, observation of the same histopathological subtype, absence of remote metastasis or peritoneal seeding, and the recurrence on the anastomotic suture line, suggesting that the cause of recurrence was the implantation of exfoliated cancer cells probably in the suture line. However, there is no established procedure for preventing implantation recurrence currently, the effectiveness of lumen lavage is suggested.

Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis.

Zygotic genome activation (ZGA) begins after fertilization and is essential for establishing pluripotency and genome stability. However, it is unclear how ZGA genes prevent mitotic errors. Here we show that knockout of the ZGA gene Zscan5b, which encodes a SCAN domain with C2H2 zinc fingers, causes a high incidence of chromosomal abnormalities in embryonic stem cells (ESCs), and leads to the development of early-stage cancers. After irradiation, Zscan5b-deficient ESCs displayed significantly increased levels of γ-H2AX despite increased expression of the DNA repair genes Rad51l3 and Bard. Re-expression of Zscan5b reduced γ-H2AX content, implying a role for Zscan5b in DNA damage repair processes. A co-immunoprecipitation analysis showed that Zscan5b bound to the linker histone H1, suggesting that Zscan5b may protect chromosomal architecture. Our report demonstrates that the ZGA gene Zscan5b is involved in genomic integrity and acts to promote DNA damage repair and regulate chromatin dynamics during mitosis.