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Abstract This case report describes a patient with mutticentric mixed type Castleman's disease and concomitant non-Hodgkin's lymphoma of diffuse large B cell type in the neck. Multicentric CD is a [...]

Background: This study aimed to explore in depth the lived experience and quality of life outcomes in patients receiving automated peritoneal dialysis (APD) treatment., Methods: The study adhered to the standards of the Consolidated Criteria for Reporting Qualitative Research. A total of 19 APD patients were recruited and assessed using in-depth semi-structured interviews on various aspects of life with respect to APD modality. The interviews were transcribed verbatim and analyzed using Interpretive Phenomenological Analysis., Results: Study findings generated five superordinate themes: (a) treatment-free daily routine, (b) sleep disturbances, (c) remote care, (d) limitations of peritoneal dialysis, and (e) the dimension of chronic disease. Further analysis of the material revealed the relationship of these themes with individual patient characteristics., Conclusions: Overall, our findings suggest that APD characteristics contribute to the perceptions of quality of life in patients under dialysis considerably., (© 2024 The Author(s). Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Background: Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer., Methods: In this case-control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI)., Results: The patients had a median age of 66 years (IQR: 58-69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression., Conclusions: ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment., Trial Registration Number: NCT04430712., Competing Interests: Competing interests: TGN has been a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, Amgen, Sanofi, Genentech, Roche, and AbbVie, outside of the current work. TGN also reports consultant fees from Bristol Myers Squibb for a Scientific Advisory Board focused on myocarditis related to immune checkpoint inhibitors. The study was funded directly by an unrestricted grant from AstraZeneca. TGN also reports research grant funding from Bristol Myers Squibb for work related to immune checkpoint inhibitors. BF reports unrelated grant support from MedImmune/AstraZeneca and MedTrace, as well as grants from NIH/NHLBI outside the submitted work. JT reports speaker’s bureau Siemens Healthcare GmbH and speakers bureau Bayer AG, reviewer Universimed Cross Media Content GmbH, and consultant Core Lab Black Forrest GmbH, all unrelated to this work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Conventional photon radiation therapy (RT) for breast cancer is associated with a reduction in global longitudinal strain (GLS) and an increase in troponin, N-terminal pro hormone B-type natriuretic peptide (NT-proBNP), and incident heart failure. The cardiac radiation exposure with proton-RT is much reduced and thus may be associated with less cardiotoxicity. The objective was to test the effect of proton-RT on GLS, troponin, and NT-proBNP., Methods and Materials: We conducted a prospective, observational, single-center study of 70 women being treated with proton-RT for breast cancer. Serial measurements of GLS, high-sensitivity troponin I, and NT-proBNP were performed at prespecified intervals (before proton-RT, 4 weeks after completion of proton-RT, and again at 2 months after proton-RT)., Results: The mean age of the patients was 46 ± 11 years, and the mean body mass index was 25.6 ± 5.2 kg/m 2 ; 32% of patients had hypertension, and the mean radiation doses to the heart and the left ventricle (LV) were 0.44 Gy and 0.12 Gy, respectively. There was no change in left ventricular ejection fraction (65 ± 5 vs 66 ± 5 vs 64 ± 4%; P = .15), global GLS (-21.7 ± 2.7 vs -22.7 ± 2.3 vs -22.8 ± 2.1%; P = .24), or segmental GLS from before to after proton-RT. Similarly, there was no change in either high-sensitivity troponin or NT-proBNP with proton-RT. However, in a post hoc subset analysis, women with hypertension had a greater decrease in GLS after proton-RT compared with women without hypertension (-21.3 ± 3.5 vs -24.0 ± 2.4%; P = .006)., Conclusions: Proton-RT did not affect LV function and was not associated with an increase in biomarkers. These data support the potential cardiac benefits of proton-RT compared with conventional RT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS., Objectives: This study aimed to detail the role of GCS and GRS in ICI myocarditis., Methods: In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death., Results: Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002)., Conclusions: GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health (P30CA008748 to DG and CLC; R01HL137562, R01HL130539; and T32HL007208-39 to DAZ). Dr Mahmood has received consultancy fees from Health and Wellness Partners, OMR Globus, Alpha Detail, and Opinion Research Team. Dr Zhang is consultant for MERCK. Dr Sullivan has served as a consultant for Merck and Novartis. Dr Heinzerling has received consultancy, advisory board, and speaker fees from Merck Sharp & Dohme, BMS, Roche, Novartis, Amgen, Sun Pharma, Pierre Fabre, and CureVac. Dr Gavira has received research support from Amgen. Dr Zubiri has served as a consultant to Merck and is supported by a SEOM (Sociedad Española de Oncología Médica) grant. Dr Yang has received research funding from CSL Behring. Dr Nohria has received research support from Amgen and has been a consultant for Takeda Oncology, Boehringer Ingelheim, and AstraZeneca; and he has received support from the Catherine Geoff Fitch fund and Gelb Master Clinician Fund. Dr Fradley has received consulting fees from AstraZeneca and Abbott and has received a research grant from Medtronic. Dr Neilan is supported by a gift from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, and a Hassenfeld Scholar Award; has received advisory fees from AbbVie, Amgen, C4 Therapeutics, H3-Biomedicine, Genentech, Roche, BMS, and Intrinsic Imaging; has received grant funding from AstraZeneca; and he is also supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL130539, R01HL137562, K24HL150238). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. All rights reserved.)

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve outcomes among patients with established heart failure. Despite supportive basic science studies, there are no data on the value of SGLT2 inhibitors among patients treated with anthracyclines., Objectives: This study sought to test the cardiac efficacy and overall safety of SGLT2 inhibitors in patients treated with anthracyclines., Methods: This study identified 3,033 patients with diabetes mellitus (DM) and cancer who were treated with anthracyclines. Cases were patients with cancer and DM who were on SGLT2 inhibitor therapy during anthracycline treatment (n = 32). Control participants (n = 96) were patients with cancer and DM who were also treated with anthracyclines, but were not on an SGLT2 inhibitor. The primary cardiac outcome was a composite of cardiac events (heart failure incidence, heart failure admissions, new cardiomyopathy [>10% decline in ejection fraction to <53%], and clinically significant arrhythmias). The primary safety outcome was overall mortality., Results: Age, sex, ethnicity, cancer type, cancer stage, and other cardiac risk factors were similar between groups. There were 20 cardiac events over a median follow-up period of 1.5 years. The cardiac event incidence was lower among case patients in comparison to control participants (3% vs 20%; P = 0.025). Case patients also experienced lower overall mortality when compared with control participants (9% vs 43%; P < 0.001) and a lower composite of sepsis and neutropenic fever (16% vs 40%; P = 0.013)., Conclusions: SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines. Additionally, SGLT2 inhibitors appeared to be safe. These data support the conducting of a randomized clinical trial testing SGLT2 inhibitors in patients at high cardiac risk treated with anthracyclines., Competing Interests: Funding Support and Author Disclosures This work was supported by National Institutes of Health/National Heart, Lung, Blood Institute (T32HL076136 to Drs Gongora and Zafar; R01HL137562, R01HL130539, and K24HL150238 to Dr Neilan). Dr Drobni has received support from the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund (ÚNKP-21-4-I-SE). Dr Zlotoff has received consulting fees from Bristol Myers Squibb and Freeline Therapeutics. Dr Armand has been a consultant for Merck, Bristol Myers Squibb, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, AstraZeneca, and Genentech; and has received honoraria form Merk and Bristol Myers Squibb. Dr Thavendiranathan has received support from the Canadian Institutes of Health Research New Investigator Award (147814) and a Canada Research Chair in Cardio-oncology; and has received speaker fees from Amgen, Boehringer Ingelheim, and Takeda. Dr Neilan has served as the Michael and Kathryn Park Chair in Cardiology; has received support from A. Curtis Greer and Pamela Kohlberg, Christina and Paul Kazilionis, and a Hassenfeld Scholar Award; has been a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, H3-Biomedicine, AbbVie, C4-Therapeutics, Roche, and Genentech, outside of the current work; has received consulting fees from Bristol Myers Squibb for a Scientific Advisory Board and consultancy focused on myocarditis related to immune checkpoint inhibitors; and has received grant funding from AstraZeneca and Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This study aims to evaluate the efficacy of the Pooled Cohort Equation (PCE), U.S. Preventative Services Task Force (USPSTF), and Framingham Risk Score (FRS) models in predicting ASCVD events among patients receiving radiation therapy (RT) for head and neck cancer (HNCA). From a large cohort of HNCA patients treated with RT, ASCVD events were adjudicated. Observed vs. predicted ASCVD events were compared. We compared rates by statin eligibility status. Regression models and survival analysis were used to identify the relationship between predicted risk and post-RT outcomes. Among the 723 identified patients, 274 (38%) were statin-eligible based on USPSTF criteria, 359 (49%) based on PCE, and 234 (32%) based on FRS. During follow-up, 17% developed an ASCVD, with an event rate of 27 per 1000 person-years, 68% higher than predicted (RR 1.68 (95% CI: 1.02, 2.12), p < 0.001). In multivariable regression, there was no difference in event rates by statin eligibility status (p > 0.05). Post-RT, the observed event rate was higher than the predicted ASCVD risk across all grades of predicted risk (p < 0.05) and the observed risk of an ASCVD event was high even among patients predicted to have a low risk of ASCVD. In conclusion, current ASCVD risk calculators significantly underestimate the risk for ASCVD among patients receiving RT for HNCA.

Aim: The aim of the present study was the qualitative comparison of working memory capacity of young children and older adults through the investigation of the latent structure stability or change in Working Memory capacity (WM) in childhood and aging, using Multiple Group Confirmatory Factor Analysis (MGCFA)., Method: The sample consisted of 62 kindergarten and 56 elementary school students (age range: 4-8 years) and 52 young-old adults and 54 old-old adults (age range: 60-94 years). Adults were asked to complete the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale-15 (GDS-15) as screening tests. The children were examined via the Raven Colored Progressive Matrix (CMP) test for the same reason. WM was examined via four measures of Working Memory Test Battery for Children (WMTB-C)., Results: MGCFA applied to the data of the kindergarten students' subsample, elementary school students' subsample, young-old and old-old adults' subsamples as well as of older adults with low (0-9 years of education) educational level. Initially, through MGCFA, four "models" were confirmed, one for each age-related subsample, and they were different from each other. However, when the same method was applied exclusively to young-old and old-old adults with low educational level, the models that emerged were similar to the kindergarten students' model., Conclusion: When we "keep" the educational level equal (low) for all, the hypothesis of retrogenesis is confirmed. Cognitive reserve appears to be protective, keeping differentiated WM's components in every age group other than that of kindergarten students. The results support the "retrogenetic" hypothesis, mainly due to the finding of a delay in WM components' development in the group of kindergarten students, and their dedifferentiation in the low-educated young-old and old-old adults.

Background: Lesions of the tongue have a broad differential diagnosis ranging from benign idiopathic processes to infections, cancers, and infiltrative disorders. An important thing to remember is that most tongue lesions will resolve spontaneously or with simple therapy within a week, if not, they should be biopsied or evaluated further for a definitive diagnosis of a potentially serious disorder. Some tongue lesions may be clues to other underlying illnesses which require further evaluation Tongue lesions are traditionally evaluated by surgical biopsy. Most of them, however, are easily accessible by fine-needle aspiration (FNA) or brushing., Study Design: Fifteen males and twelve females aged from 15 to 72 were examined in our institution over a period of 15 years and 27 lesions, were evaluated by fine-needle aspiration cytology (FNAC) or brushing cytology., Results: The lesions were located at the mobile aspect of the tongue.10 malignant tumors were diagnosed: 9 cases of squamous cell carcinoma (SCC), and 1 non-Hodgkin lymphoma (NHL). In addition, 13 benign tumors (7 cases of papillomas / fibromas, 3 cases of hemangiomas, 2 cases lymphangiomas, and 1 case of lipoma), and 4 nonneoplastic benign conditions (3 traumatic ulcers and 1 hematoma) were found. There were no false-positive diagnoses. There were no clinical complications resulting from FNA or brushing., Conclusion: Cytologic examination is rapid, safe, accurate, inexpensive, and patient-friendly for establishing preoperative diagnosis in tumors and tumor-like conditions of the tongue, and we recommend this method as the first diagnostic step in the evaluation of these lesions.

Objective: The accessory parotid gland is salivary tissue separated from the main parotid gland and lying on masseter muscle. It has secondary duct emptying into the Stensen's duct. The accessory parotid gland exists in 21-61% of individuals. However, the appearance of an accessory parotid tumor is rare, with a reported frequency of 1-7.7% of all parotid gland tumors. Carcinoma ex pleomorphic adenoma arises from a pre-existing benign mixed tumor. Most of these tumors will have malignant epithelial component, but not malignant stromal component. Reports of Fine Needle Aspiration Cytological (FNAC) diagnosis of malignant mixed tumor are uncommon and have been limited to cases arising in the parotid. We report a case of carcinoma ex pleomorphic adenoma of the accessory lobe of the parotid, and address the cytopathology features and pitfalls of this condition., Case: A 73 aged female presented with a right nontender midcheek mass. The lesion had been present 18 months, with a recent increase in size. FNA was performed and the smears demonstrated features indicative of pleomorphic adenoma admixed with findings indicative of a poorly differentiated carcinoma., Conclusion: FNAC can accurately diagnose carcinoma ex pleomorphic adenoma when strongly fixed requirements are implemented.

Touch imprint cytological diagnosis of nodal Langerhans cell histiocytosis. Langerhans cell histiocytosis (LCH) is a rare neoplasm of the mononuclear phagocytic immunoregulatory system of unknown aetiology. Nodal involvement is uncommon. Cytological findings have seldom been described. A case study of LCH, arising in a submandibular node of a 42-year-old female, is reported. Fine needle aspiration smears were highly cellular and composed of a mixed cell population including eosinophils, lymphocytes, neutrophils, and macrophages. Imprint slides from the surgical specimen of the excised node exhibited Langerhans cells with nuclear grooves, leading to a diagnosis suggestive of LCH. Immunohistochemical staining of the node sections with CD1a and S-100 confirmed this diagnosis. In conclusion, cytology may favorably contribute to the diagnosis of LCH.

Background: The improvement in quality of cytological preparations with the use of LBP methodology has been well-documented, but the cytological artifacts resulting from this technique have not been adequately described. This study describes and illustrates the cytological artifacts introduced by LBP technique when used on fine-needle aspirates (FNAs), and evaluates these artifacts as potential diagnostic pitfalls., Study Design: We reviewed a total of 96 FNAs simultaneously processed by both conventional smears and LBP. FNAs were obtained from the following sites: lymph node (38), breast (28), soft-tissue sites (nine), salivary glands (six), and thyroid gland (15)., Results: The LBP smears were consistently devoid of obscuring elements, and the cells were adequately preserved and evenly dispersed. However, we noted some cytomorphological alterations that should be recognized to avoid erroneous diagnoses. The size of cell clusters was decreased, large branching sheets were fragmented, and there were more single cells, resulting in apparent discohesion. Small cells such as lymphocytes tended to aggregate. All cells were generally smaller and occasionally spindled, the chromatin detail was attenuated, and nucleoli were more prominent. Intranuclear inclusions were difficult to visualize. Background matrix was often altered in both quantity and quality. Extracellular particles, small mononuclear cells, red blood cells, and myoepithelial cells were markedly decreased in number., Conclusions: Cytopathologists should be careful in interpreting FNAs prepared using LBP technique if that is the only methodology employed. Familiarity with artifacts is essential to avoid misdiagnoses.

Objective: Endometriosis is defined as functioning endometrial tissue outside the uterine cavity. It occurs in up to 15% of menstruating females and in most cases is located within the pelvis. Endometrial implants, however have been described in soft tissues, particularly in the skin and subjacent tissues of surgical scars, and diagnosis might be problematic., Case Study: A 32 aged female presented with a suprapubic abdominal mass, which appeared suddenly after exercise. Fine needle aspiration was performed., Results: Epithelial sheets were shown in direct aspirates. No evident endometrial stromal cells were seen. CD10 immunostaining in additional cell block preparations using a commercial antibody gave positive results. The cell pattern and immunocytochemical profile suggested a cytodiagnosis of endometriosis. The patient was administered with leuprolide acetate. She experienced adverse effects related to estrogen deficiency. Medical treatment was discontinued and the patient underwent surgical excision. Histological sections revealed endometrial glands surrounded by stroma and embedded in fibrous connective tissue., Conclusion: With optimal preparations a confident cytological diagnosis of endometriosis may be established easily, allowing correct treatment of the disease and, in selected cases, planning of preoperative pharmacologic therapy.

Objective: Benign and malignant lesions of the breast may have similar appearances on fine-needle aspiration cytology. We report a case of fibroadenoma that was diagnosed as carcinoma by cytology., Case Study: Breast fine-needle aspiration biopsy was highly cellular and composed of bland-appearing spindle/columnar cells that could represent either epithelial or stromal cells; the case was reported as positive and the patient had subsequent excisional biopsy taken., Results: On microscopic examination, smears were hypercellular and had many single cells and clusters of columnar/ elongate cells No obvious bipolar cells of myoepithelial origin were seen. Significant atypia was noted. Immunocytochemistry for smooth muscle actin was not performed due to insufficient material., Conclusions: Some cases of fibroadenoma and carcinoma can be very difficult to distinguish on fine needle aspiration cytology smears. Immunocytochemistry may be of help if sufficient material is provided. To avoid false positive diagnosis on cytology, it is best to report such a case as intermediate (atypical/suspicious) with final interpretation pending excisional biopsy.

Background: The exact biological function of CD30 in the thymus during development has been only partially elucidated, although data indicate it may be involved in negative selection. This study was prompted by the observation of a positive reaction of thymic epithelial cells (TECs), Hassall's corpuscles, and thymocytes with the monoclonal antibody CD30 during the late first and second trimester., Material/methods: Twenty paraffin-embedded fetal thymus specimens at the late first and second trimester were investigated by conventional histology and immunohistology for CD30 expression. To provide additional information on the nature and localization of CD30+ thymocytes and CD30+ TECs, in situ hybridization (ISH) was performed on the specimens., Results: 1) In the medulla, a statistically significant difference between CD30+ thymocytes from the late first trimester and those from the second trimester (p<0.0001, t-test) was demonstrated. No significant difference was found concerning CD30+ thymocytes in the cortex. 2) Many medullary TECs and Hassall's corpuscles showed high expression of CD30 during the second trimester, whereas small numbers of CD30+ TECs were found during the late first trimester. No statistically significant difference was found concerning CD30+ TECs in the cortex. CD30 was expressed by ISH in many cells in the medulla and along the septa, whereas the cortex showed little if any expression. Accordingly, a higher CD30 expression was found in medullary than in cortical thymocytes., Conclusions: Comparison of CD30 expression by TECs and thymocytes during the late first trimester and second trimester suggests an important role for CD30 in thymic selection.

Unlabelled: Once lymphoid precursors enter the thymus form the blood stream, they come into contact with thymic stromal cells that guide their maturation into functionally competent T cells. Thymic myoid cells are one such cell type. They have been described as a regular constituent of the thymus of embryonic and young vertebrates and express muscle proteins including myosin, desmin, acetylcholine receptor (AChR), C-protein, MyoD, troponin T, rapsyn, and utrophin. It has been emphasized recently that the thymic myoid cells play an important role in the protection of thymocytes from apoptosis, and in the process of T-cell differentiation and maturation., Aim: To provide a quantitative estimation of thymic myoid cells and T-cell population in different stages of development. A probable interaction between these two populations could explain an additional mechanism to the active T-cell migration from the thymus that is a direct contact to a specific myoid cell line., Materials and Methods: Paraffin-embedded specimens from the thymus of forty five human embryos at the first, second and third trimester of gestation respectively, were investigated by conventional histology, and immunohistology for the presence in the stroma of the thymic medulla, of myosin in the myoid cells, and UCHL1 (pan T-cell) antigen in the medullary thymocytes., Results: Our results demonstrated a quantitative difference in the second and third trimester of development concerning the expression of myosin in the stromal myoid cells of the thymic medulla over the equivalent expression of the protein in the first trimester. Similar changes in the above periods were found concerning the population of medullary thymocytes expressing UCHL1 antigen., Conclusions: Our results indicate that: (1) Thymic myoid cells play an important role in the thymic microenvironment as they are well conserved throughout species evolution. (2) The increased population of myoid cells in the medullary area during mid and late gestational age, in comparison with first trimester, probably reflects the increased demand of the growing fetus for mature T lymphocytes. Contractions of myoid cells mediated by their cytoplasmic structural proteins, including myosin which is well preserved during development, might aid the movement of thymocytes expressing UCHL1 antigen, across or out of the gland, suggesting a potential involvement of myoid cells in the thymic function. Further studies on larger series are needed to corroborate this.

Low-grade non-Hodgkin's lymphomas (NHL) of mucosa associated lymphoid tissue (MALT) are indolent neoplasms that, although tending to remain localized for many years, may spread to other mucosal sites. Despite increasing identification of concurrent gastric and intestinal lymphoma of MALT type, the clonal relationship between the tumors and their sequential development are poorly understood. It is also unknown whether the development of these concurrent tumors is closely associated with direct antigen stimulation, which is thought to play an important role in the clonal expansion of low grade MALT lymphomas. The most important function of B-cells is production of specific antibodies. This is largely achieved during B-cell development by recombination of the Ig heavy chain variable (V), diversity (D), and joining (J) segments and hypermutation of the rearranged gene. The rearranged Ig genes of a mature B-cell record much of its evolution history. We report a case of synchronous development of intestinal and gastric low grade MALT lymphomas in a 70 years old female and discuss their possible clonal relationship and sequential appearance.

Solid mural nodule within a mucinous cystic ovarian tumor occurs more often than generally presumed. One especially interesting case involving coincidental cervical carcinoma is presented. A 38-year-old woman underwent exploratory laparotomy for a right ovarian tumor. After ovarian malignancy had been diagnosed from frozen section, the bilateral salpingo-oophorectomy and hysterectomy was performed. The tumor had a unilocular cystic cavity and a mural nodule. The nodule showed undifferentiated carcinomatous features. The immunohistochemical examination revealed atypical cells in the nodule which were positive for cytokeratin, CEA, and vimentine, establishing its anaplastic nature. A synchronous cervical invasive squamous carcinoma was documented. The patient was treated with chemotherapy and radiotherapy. Currently, at 15 postoperative months, she is well and free of disease. The occurrence of ovarian mucinous cystadenocarcinoma with mural nodule of anaplastic carcinoma and cervical squamous cell carcinoma is evidently very uncommon, because we have not found a similar case in the literature.

Objective: Serous papillary carcinomas of the endometrium are aggressive tumors that tend to permeate, in a very extensive fashion, to uterine and adnexal lymphatic and vascular channels at an early stage in their evolution, and are associated with a particularly gloomy prognosis. It is generally thought that even tumors apparently limited to the endometrium or confined to an endometrial polyp have a poor outcome. Our study points towards the value of HLA-DR antigen in the outcome of serous papillary endometrial cancer. Our aim was to assess the HLA-DR expression in inactive, endometrial intraepithelial carcinoma (EIC), and invasive serous carcinoma curretage specimens from the endometrial cavity, suggesting a role in immune response to keep tumor proliferation in check., Study Design: Thirty-one cases of inactive endometrium, twelve cases of EIC, and thirty-nine cases of serous papillary invasive carcinoma curettings were evaluated for the detection of HLA-DR monoclonal antigen. T helper (TH) marker (CD4) in the tumor stroma of the relevant cases was also studied, given that it is now known that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to TH cells., Results: HLA-DR was expressed in 20 of 31 inactive endometrium (64.5%), 4 of 12 in EIC (33.3%), and in 10 of 39 serous papillary invasive carcinomas (25.6%). CD4 was expressed in 9 of 31 inactive endometrium (29%), 5 of 12 in EIC (42%), and in 26 of 39 serous papillary invasive carcinomas (67%)., Conclusions: The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells of inactive endometrium, of EIC and of serous papillary invasive carcinomas agrees with the hypothesis of the inactive endometrium - carcinoma in situ sequence as the usual route for the development of serous papillary invasive carcinoma. The immune attract mechanism by low HLA-DR signaling seems to be of minor importance in the malignant and metastatic potential of the serous papillary endometrial tumours.

Background: Ki-1 (CD30) antigen expression is not found on peripheral blood cells but its expression can be induced in vitro on T and B lymphocytes by viruses and lectins. Expression of CD30 in normal tissues is very limited, being restricted mainly to a subpopulation of large lymphoid cells; in particular, cells of the recently described anaplastic large cell lymphoma (ALCL), the Reed-Sternberg (RS) cells of Hodgkin's lymphoma and scattered large parafollicular cells in normal lymphoid tissues. More recent reports have described CD30 expression in non-hematopoietic and malignant cells such as cultured human macrophages, human decidual cells, histiocytic neoplastic cells, mesothelioma cells, embryonal carcinoma and seminoma cells., Results: We investigated the immunohistochemical expression of CD30 antigen in 15 paraffin-embedded tissue samples representing small intestines from fetuses after spontaneous abortion in the 8th, 10th and 12th weeks using the monoclonal antibody Ki-1. Hormones had been administered to all our pregnant women to support gestation. In addition, a panel of monoclonal antibodies was used to identify leukocytes (CD45/LCA), B-lymphocytes (CD20/L-26) and T-lymphocytes (CD3). Our findings were correlated with those obtained simultaneously from intestinal tissue samples obtained from 15 fetuses after therapeutic or voluntary abortions., Conclusions: The results showed that: (1) epithelial cells in the developing intestinal crypts express the CD30 (Ki-1) antigen; (2) CD30 expression in these epithelial cells is higher in cases of hormonal administration than in normal gestation. In the former cases (hormonal support of gestation) a mild mononuclear intraepithelial infiltrate composed of CD3 (T-marker)-positive cells accompanies the CD30-positive cells.

Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin's lymphoma (WHO classification) that mainly develops in HIV infected males, more frequently in homosexuals and advanced stages of the disease (total CD4+ lymphocyte count below 100-200/microL). Occasionally, it appears in other immunodepressive states (such as solid organs transplant period) and even, although very rarely, in immunocompetent patients. From a pathogenetic point of view, PEL has been related to Kaposi's sarcoma associated herpes virus (also named human herpesvirus 8, HHV-8), an etiological factor of Kaposi's sarcoma. The relative infrequency of this disease, the absence of wide casuistics allowing a better characterization, and its unfavorable outcome support the need of a deeper knowledge. We present here the clinical-biological findings of a patient, HIV seronegative, who was diagnosed with peritoneal PEL of T-cell origin, and not HHV-8-associated, five years after renal transplantation.

We report a case of a patient with inflammatory pseudotumor (IPT) of the spleen. IPTs can appear at many sites and represent rear lesions of uncertain etiopathogenesis. Usually they present as mass lesions, so the clinical and radiologic features often suggest malignancy. However, the microscopic findings are quite characteristic, and the diagnosis can be made readily by identifying the reactive nature of the cells. Diagnostic problems can arise when these lesions occur in lymphoid organs or the spleen.

Personal experience in the treatment of a female patient presenting a pure monolobar Caroli's disease, is described. The woman was asymptomatic so far; during the last 2 weeks she was admitted on 3 occasions with repeated attacks of cholangitis and obstructive jaundice. Surgery was performed for relief of the jaundice. A diagnosis of segmental Caroli's disease (congenital dilatation of intrahepatic bile ducts) with congenital fibrosis was made on the basis of marked fibrous septa with the characteristic ductal plate formation on left hepatectomy specimen and the cysts seen on ultrasound.

Aim: To determine the expression of CMV-associated antigen in the human decidual endometrial stromal cells in spontaneous abortions with no evidence of maternal relapse during the first trimester of gestation., Experimental Design: We examined 15 placentas resulting from intrauterine fetal death after spontaneous abortion during the 8th, 10th, and 12th week of gestation respectively, and in which CMV reactivation was ruled out from serological evaluation of the pregnant women at admission, versus equal controls after voluntary abortion following well-documented maternal viral recurrence. In addition, a panel of monoclonal antibodies for the identification of leukocytes (CD45/LCA), B-lymphocytes (CD20/L-26), and T-lymphocytes (CD45RO/UCHL1), was performed. All women received hormonal medication to support gestation, in the cases of spontaneous abortions., Results: Immunohistochemical examination using a specific antibody against cytomegalovirus showed large multinucleated infected cells with intranuclear inclusions, located primarily in the decidual stroma within a lymphoplasmacytic infiltrate in the cases of spontaneous abortions. No evidence of infection was observed in the chorionic villi. In the cases of voluntary abortions same findings were observed in the relevant areas, and a strong evidence of infection was observed in the chorionic villi., Conclusion: This study demonstrates 1) that the decidual endometrial stromal cells can express the CMV-associated antigen prior to serological manifestation of the viral replication, 2) the expression of the antigen is higher in cases of hormonal administration to support gestation. In these cases a mild mononuclear infiltrate of UCHL1 (T marker) positive cells, accompanies the CMV-associated antigen positive cells.

Aim: To detect whether preeclampsia influences neonatal intrahepatic hematopoiesis, given that an activation of fetal neutrophils and monocytes during the course of this disorder occurs., Experimental Design: We examined liver samples from 10 neonates of hypertensive/preeclamptic women at 27 to 28 weeks of gestation delivered by a cessarian section. All neonates were placed in incubators but they all died within 24 hours due to immaturity. The control group comprised 10 fetuses of the same gestational age, after voluntary abortion due to a neural defect. Specific antibodies against CD34, glycophorin C, hemoglobins A and F, myeloperoxidase, CD61, CD68, terminal desoxynucleotidyl transferase and the pax-5/B-cell specific activator protein, were used in each sample., Results: Neonates from hypertensive/preeclamptic women, in comparison with controls, showed: a statistically significant reduction of erythropoiesis by 25% (p=0.015); a statistically significant increase of granulopoiesis (p=0.019); a statistically significant increase in the expression of CD68 positive cells of the monocytic lineage (p=0.017); a statistically significant increase in the expression of CD34 progenitor/stem positive cells (p=0.021). No statistically significant differences were observed in both examined groups, concerning megakaryopoiesis and B lymphopoiesis., Conclusions: Preeclampsia of pregnancy has an impact on neonatal intrahepatic hematopoiesis by increasing granulopoiesis, reducing erythropoiesis and triggering endothelial and stem cell activation. We suggest that these findings reflect a state of persistent inflammation and a loss of red blood cell production possibly contributing to the neonatal morbidity related to this disorder.