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AbstractPurpose: To describe the characteristics of pancreatoblastoma. Material and Methods: We studied 3 cases of pancretoblastoma and reviewed another 59 cases. Parameters analyzed were tumor site, hemorrhage, capsule formation, necrosis, vascularity, production of alpha-fetoprotein (AFP), cystic changes and calcification. Results: The diagnostic findings were as follows: pancreatic head origin (24/54, 44%), pancreatic body and tail origin (30/54, 56%), hemorrhage (16/17, 94%), capsule formation (24/26, 92%), necrosis (28/31, 90%), hypervascularity (10/14, 71%), production of AFP (19/28, 68%), cystic changes (11/16, 69%), and calcification (10/21, 48%). All neonatal cases demonstrated cystic changes. Three of them were patients with Beckwith-Wiedmann syndrome. The incidence of capsule formation and calcification was not related to the origin of the tumor. Conclusion: The most common features of pancreatoblastoma are hemorrhage, capsule formation and necrosis. [ABSTRACT FROM AUTHOR]

Semiquantitative analysis of lactoferrin deficiency in neutrophil polymorphonuclear leucocytes in various haematological and non-haematological disease was carried out by scoring polymorphonuclear leucocytes stained for lactoferrin by the immunoperoxidase method. The staining patterns for lactoferrin were classified into four types (0-III) based on the intensity of reaction, and the sum of the ratings of 100 polymorphonuclear leucocytes was considered as "lactoferrin score" with a possible range of 0-300. As a result, significantly low lactoferrin-scores were frequently observed in acute leukaemias and the acute phase of chronic leukaemias. Of 35 cases with leukaemias, lactoferrin-negative polymorphonuclear leucocytes (type 0) were observed in the following cases: eight cases of acute myelogenous leukaemia (8/14), a case of chronic myelogenous leukaemia (1/10) in blast crisis, one of acute promyelocytic leukaemia (1/1), one of acute monocytic leukaemia (1/2), and a case of chronic myelomonocytic leukaemia (1/2) in a transitional phase to an acute myelomonocytic leukaemia. In two cases of acute myelogenous leukaemia, in which the majority of polymorphonuclear leucocytes were negative for lactoferrin, ultrastructural cytochemical study revealed total lack of specific granules in these polymorphonuclear leucocytes. This suggests that lactoferrin is localised in the specific granules of neutrophils as has been postulated previously by others. [ABSTRACT FROM PUBLISHER]

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) exhibits hematological features that are indistinguishable from those of acute megakaryoblastic leukemia. However, TAM typically resolves spontaneously within several months postnatally. Some patients with TAM, however, develop severe clinical manifestations, which can lead to an unfavorable prognosis. TAM originates in utero through the acquisition of somatic GATA1 mutations, resulting in the loss of the full-length GATA1 protein and excessive production of the N-terminal truncated short isoform of the GATA1 protein (GATA1s). Herein, we report the pathological findings from an autopsy of a female stillbirth with TAM and DS, including an examination of her placental tissues. Immunohistochemical analysis revealed the expression of GATA1s, but not full-length GATA1, in CD42b-positive atypical immature megakaryocytes and blasts in the placental blood vessels. This confirms the diagnosis of TAM and suggests the utility of placental tissue for histological diagnosis. Additional unique findings from the autopsy specimens are discussed., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

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., (© 2024. Japanese Society of Hematology.)

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., Competing Interests: Declaration of Competing Interest Nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2021. The Author(s).)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

A liposarcoma is extremely rare in the digits. A 73-year-old woman was diagnosed with a lipoma in her middle finger 10 years ago. As this tumor increased in size and presented with imaging findings that were atypical of lipomas, careful marginal resection biopsy outside the pseudo-capsule was performed, and the tumor was diagnosed as a well-differentiated liposarcoma. At the 5-year follow-up, the patient showed no evidence of local recurrence or metastasis, with no loss of hand function. The findings from this case suggest that even for a lipomatous tumor in the digits, further imaging examination and resection biopsy should be considered if the tumor presents with features that are atypical of lipomas.

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.

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.

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., (© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

A 67-year-old man presented with a fever and general malaise. Computed tomography showed multiple nodules in the lungs and liver, associated with mediastinal and para-aortic lymphadenopathy. Bone marrow aspiration revealed diffuse large B-cell lymphoma (DLBCL). Renal and liver dysfunction and pancytopenia inhibited chemotherapy administration; the patient subsequently died of multiorgan failure. An autopsy revealed pulmonary adenocarcinoma with metastases to the lungs, liver, and adrenal glands; the DLBCL spread to the liver, spleen, and bone marrow. Adenocarcinoma and DLBCL collision was observed in the mediastinal and para-aortic lymph nodes. This was a rare case of collision metastasis occurring in the lymph node.

Liver fibrosis is a common complication associated with transient myeloproliferative disorder (TMD) in Down syndrome (DS). The exact molecular pathogenesis that regulates disease progression is largely unknown. We recently found serum and/or urinary monocyte chemoattractant protein-1 (MCP-1) as a novel biomarker of liver fibrosis. This study was an in vitro analysis to investigate the fibrogenic activity of MCP-1 using the collagen-producing LX-2 human hepatic stellate cell line. We also examined the fibrogenic activity of serum from a male neonate with DS in whom late-onset liver fibrosis developed even after the resolution of TMD. MCP-1 stimulated both cell growth and collagen synthesis of LX-2 in a dose-dependent manner. Patient serum obtained during the active disease phase significantly up-regulated fibrogenic activity, which was suppressed in the presence of MCP-1-blocking antibody. Transient transforming growth factor beta 1 stimulation primed LX-2 to induce prolonged hypersecretion of MCP-1 in the culture supernatant and in collagen synthesis, which was suppressed with MCP-1 blocking antibody as well. Conclusion: MCP-1 accounts for the prolonged activation of collagen-producing hepatic stellate cells in both a paracrine and autocrine manner, thereby promoting liver fibrosis. Anti-cytokine therapy targeting the fibrogenic cytokines of MCP-1, for example, herbal medicine, could provide a new therapeutic intervention for liver fibrosis associated with TMD in DS. ( Hepatology Communications 2018;2:230-236).

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.

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., (© 2017 S. Karger AG, Basel.)

We report a case of a 64-year-old woman with anaplastic carcinoma of the pancreas (ACP) with cyst formation and review 60 ACP cases reported in Japan. In 20% of cases, laboratory tests revealed severe anemia (hemoglobin level < 10.0 g/dL) and elevated leucocyte counts (> 12000/mm 3 ), which were likely attributable to rapid tumor growth, intratumoral hemorrhage, and necrosis. Elevated serum CA19-9 levels were observed in 55% of cases. Cyst-like structures were observed on imaging in 47% of cases, and this finding appears to reflect subsequent cystic degeneration in the lesion. Macroscopically, hemorrhagic necrosis was observed in 77% of cases, and cyst formation was observed in 33% of cases. ACP should be considered when diagnosing pancreatic tumors with a cyst-like appearance, especially in the presence of severe anemia, elevated leucocyte counts, or elevated serum CA19-9 levels., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest.