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Head and Neck Pathology Jun 2024Previous studies have shown that at least a of intraoral eosinophilic ulcer is best classified as a CD30 + T-cell lymphoproliferative disorder (LPD), with... (Review)
Review
BACKGROUND
Previous studies have shown that at least a of intraoral eosinophilic ulcer is best classified as a CD30 + T-cell lymphoproliferative disorder (LPD), with histopathology reminiscent of lymphomatoid papulosis (LyP) of the skin. Microscopically, a mixed population of inflammatory cells, often including eosinophils and varying numbers of atypical lymphoid cells, frequently expressing CD30, is typical for LyP, whose clinicopathological spectrum includes type A, B, C, D, E, and LyP with DUSP22/IRF4 rearrangement. To date, about 27 intraoral LyP cases have been reported. Of them, 7 cases were diagnosed as LyP type C, which is frequently confused with anaplastic large cell lymphoma (ALCL) on histopathology.
METHODS
A 60-year-old male was referred for a one-month history of a tongue ulcer.
RESULTS
Microscopy showed numerous subepithelial atypical large lymphoid cells, which expressed CD4 (with partial loss of CD3, CD5, and CD7), CD8 (few cells), CD30 (about 50%, in non-diffuse pattern with size variability), TIA-1, and Ki-67 (85%), without staining for CD56, ALK, LMP1, and EBER1/2, concerning for a diagnosis of ALCL. However, after three weeks, the lesion completely healed.
CONCLUSION
We present here a rare case of intraoral CD30+ T-cell LPD that we believe is the oral counterpart of cutaneous LyP type C.
Topics: Humans; Male; Lymphomatoid Papulosis; Middle Aged; Ki-1 Antigen; Diagnosis, Differential; Immunohistochemistry; Lymphoproliferative Disorders; Biomarkers, Tumor; T-Lymphocytes
PubMed: 38941041
DOI: 10.1007/s12105-024-01664-z -
Gut Microbes 2024Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the...
Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.
Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.
Topics: Animals; Receptors, CXCR6; Chemokine CXCL16; Mice; Fecal Microbiota Transplantation; Humans; Gastrointestinal Microbiome; Liver; Lymphocytes; Mice, Inbred C57BL; Male; Immunity, Innate; Fatty Liver; Interleukin-22; Non-alcoholic Fatty Liver Disease; Interleukins; Female
PubMed: 38940400
DOI: 10.1080/19490976.2024.2372881 -
Acta Endocrinologica (Bucharest,... 2023Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is...
BACKGROUND
Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is counteracted by increased collagen production, deposition and scarring. However, only recently a specific subpopulation of modified fibroblasts with contractile properties, namely "myofibroblasts" (MFBs) have been linked to HT.
AIM
Our ultrastructural study aims to delineate the presence and contribution of MFBs to the fibrotic milieu of HT.
MATERIAL AND METHODS
Tissue biopsies were obtained from 5 HT-diagnosed patients and specimens were examined using a Transmission Electron Microscope (TEM).
RESULTS
Histopathological examination indicated extensive microvilli atrophy and atypical vacuolations of the thyroid follicular cells in the HT samples. In addition to interstitial extravasated lymphocytes, capillaries were encircled by MFBs (mean distance from lumen 1.248± 0.43µm) with the characteristic electron-dense α-smooth muscle actin (α-SMA), confirmable in higher magnifications. Myofibroblastic projections were found to have significantly higher representation near the capillary lumen compared to the impaired endothelial lining (P < 0.01).
CONCLUSION
Our TEM findings suggest that the intrusion of endothelia by myofibroblastic projections can be a significant factor towards the malfunction of follicular cells in HT patients and offer a paradigmal understanding of the ultrastructural interactions that may underlie the HT pathology.
PubMed: 38933253
DOI: 10.4183/aeb.2023.415 -
Clinical Cancer Research : An Official... Jun 2024Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial...
BACKGROUND
Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited.
METHODS
Follow-up data from patients in our prospective phase II trial of LIUD for AH/G1EEC were collected from medical records. Spatial transcriptomics (Nanostring GeoMX digital spatial profiling) with in silico cell type deconvolution and pathway analyses were employed on longitudinal biopsy samples from five patients across pre-treatment, on-treatment, and relapse.
RESULTS
Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen (39%) experienced relapse. Clinical factors associated with shorter response duration included younger age, initial diagnosis of G1EEC, lack of response at six months, premenopausal status, and Hispanic ethnicity (p<0.05), but only six-month response status remained a significant predictor in a multivariate model (p=0.023). LIUD increased abundance of NK cells (DMCP-counter score=46.13, FDR=0.004) and cytotoxic lymphocytes (DMCP-counter score=277.67, FDR=0.004), as well as lymphocyte cytotoxicity markers PRF1 (log2FC=1.62, FDR=0.025) and GZMA (log2FC=2.47, FDR=0.008). NK cells were reduced at relapse (DMCP-counter score=-55.96, FDR=0.02). Immune-related pathways (IFNα-response and TGFβ-signaling) were enriched at relapse (FDR<0.05). IDO1 expression, reflecting immune exhaustion, was upregulated at relapse (FDR<0.05).
CONCLUSIONS
Upfront resistance and relapse after initial response to LIUD for AH/G1EEC impacts nearly half of patients, remaining a major hurdle for non-surgical treatment of AH/G1EEC. Molecular studies evaluating longitudinal biopsies from a small cohort implicate immune mechanisms at relapse, including reversal of progestin-related immunomodulation and increased immune exhaustion.
PubMed: 38922360
DOI: 10.1158/1078-0432.CCR-24-0362 -
Dermatopathology (Basel, Switzerland) Jun 2024Primary cutaneous lymphomas (PCLs), especially mycosis fungoides (MF), pose significant diagnostic and therapeutic challenges. This study aims to correlate initial...
Primary cutaneous lymphomas (PCLs), especially mycosis fungoides (MF), pose significant diagnostic and therapeutic challenges. This study aims to correlate initial histological features with the disease course and survival in MF patients. A retrospective-prospective cohort study was conducted on 83 patients diagnosed with early-stage MF at the Departments of Dermatovenerology and Pathology, UHC Zagreb, from January 2003 to December 2012. The analyzed histopathological parameters included lichenoid dermal lymphocyte infiltrate, Pautrier microabscesses, and lymphocyte atypia. Patients with more than 30 guardian lymphocytes per 100 keratinocytes exhibited worse overall and progression-free survival. Furthermore, those with over 50% atypical lymphocytes demonstrated a faster progression rate. A dense lichenoid dermal infiltrate and a high count of lymphocyte "keepers" significantly increased the mortality risk within five years of diagnosis. This study did not fully confirm the hypothesis regarding the prognostic value of large Pautrier microabscesses but highlighted the importance of dense lichenoid infiltrates. The study identified new potential histopathological prognostic factors in early-stage MF, suggesting the need for larger studies to confirm these findings. The identification of such predictors could enhance the prognostic stratification and guide more tailored therapeutic approaches for MF patients.
PubMed: 38921054
DOI: 10.3390/dermatopathology11020017 -
Frontiers in Medicine 2024Riehl's melanosis is a pigmented dermatitis that manifests as brown-gray facial pigmentation with pigment incontinence and infiltration of cells in the upper dermis. The...
Riehl's melanosis is a pigmented dermatitis that manifests as brown-gray facial pigmentation with pigment incontinence and infiltration of cells in the upper dermis. The associated inflammation is induced by a variety of products such as drugs and cosmetics. Henna, commonly referred to as a hypoallergenic cosmetic, has been reported to cause Riehl's melanosis in some cases. Although skin depigmenting agents have been occasionally used, satisfactory results have not been obtained and no established therapeutic strategies exist to treat Riehl's melanosis. Meanwhile, picosecond lasers effectively treat other hyperpigmentation disorders. In this study, we report safe and effective treatment of henna induced-atypical Riehl's melanosis using a 755-nm picosecond Alexandrite laser. Immunohistochemical analyses revealed a potential role of CD8-positive lymphocytes in henna-induced inflammation and hyperpigmentation of the basal layer, and a role of melanophages in the pigmented dermis of Riehl's melanosis.
PubMed: 38919937
DOI: 10.3389/fmed.2024.1401938 -
Open Life Sciences 2024Richter transformation (RT) represents the development of intrusive lymphoma in individuals previously or concurrently diagnosed with chronic lymphocytic leukemia (CLL)...
Richter transformation (RT) represents the development of intrusive lymphoma in individuals previously or concurrently diagnosed with chronic lymphocytic leukemia (CLL) and is characterized by lymph node enlargement. However, cases involving extra-nodal organ involvement as the first symptom are rare. There are no reports of RT with breast lesions as the first symptom. Nonspecific and atypical clinical manifestations represent key challenges in the accurate diagnosis and appropriate treatment of RT. This case report describes an elderly female patient who presented with breast lesions as the first RT symptom. The patient was admitted with a painless mass in the left breast. Examination revealed multiple lymphadenopathies and abnormally high white blood cell levels. The patient was diagnosed with CLL after hematological tests, assessments of bone marrow morphology, and tissue biopsy. Mammography and B-ultrasonography showed solid space-occupying lesions (BI-RADS category 5) in the left breast. Initially, the patient declined a breast biopsy and was therefore prescribed ibrupotinib treatment, which showed limited efficacy. A needle biopsy of the affected breast indicated the presence of diffuse large B-cell lymphoma. Based on auxiliary and pathological examinations and medical history, the final diagnosis was RT with breast involvement. Zanubrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment provided initial control; however, the treatment strategy required adjustment because of the patient's fluctuating condition. The current status of the patient is marked as stable, showing an overall achievement of partial alleviation. The patient is in the process of receiving follow-up treatment. We also performed a comprehensive literature review on RT, with particular emphasis on its biological paradigm, prognosis implications, existing therapeutic approaches, and emerging directions in treatment modalities.
PubMed: 38911930
DOI: 10.1515/biol-2022-0889 -
Scientific Reports Jun 2024Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic...
Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic samples. We evaluate the efficacy of DI-60 in determining white blood cell (WBC) differentials in normal and abnormal samples in different WBC count. Peripheral blood smears (n = 166) were categorised into normal control and disease groups, and further divided into moderate and severe leucocytosis, mild leucocytosis, normal, mild leukopenia, and moderate and severe leukopenia groups based on WBC count. DI-60 preclassification and verification and manual counting results were assessed using Bland-Altman and Passing-Bablok regression analyses. The Kappa test compared the concordance in the abnormal cell detection between DI-60 and manual counting. DI-60 exhibited notable overall sensitivity and specificity for all cells, except basophils. The correlation between the DI-60 preclassification and manual counting was high for segmented neutrophils, band neutrophils, lymphocytes, and blasts, and improved for all cell classes after verification. The mean difference between DI-60 and manual counting for all cell classes was significantly high in moderate and severe leucocytosis (WBC > 30.0 × 10/L) and moderate and severe leukopenia (WBC < 1.5 × 10/L) groups. For blast cells, immature granulocytes, and atypical lymphocytes, the DI-60 verification results were similar to the manual counting results. Plasma cells showed poor agreement. In conclusion, DI-60 demonstrates consistent and reliable analysis of WBC differentials within the range of 1.5-30.0 × 10. Manual counting was indispensable in examining moderate and severe leucocytosis samples, moderate and severe leukopenia samples, and in enumerating of monocytes and plasma cells.
Topics: Humans; Leukocyte Count; Leukocytes; Leukopenia; Leukocytosis; Sensitivity and Specificity; Female; Male; Neutrophils; Middle Aged
PubMed: 38906933
DOI: 10.1038/s41598-024-65427-0 -
Histopathology Jun 2024There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis...
AIMS
There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series.
METHODS AND RESULTS
Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra-epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra-epidermal lymphocytes with tagging and cytological atypia. Pautrier-like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow-up of all cases has been consistent with classical morphoea.
CONCLUSION
Early morphoea can seldom present with atypical clonal intra-epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated.
PubMed: 38890785
DOI: 10.1111/his.15246 -
International Journal of... 2024Typically, lymphatic tissue proliferative lesions include either benign lesions or lymphoma. However, not all lymphatic lesions can currently be accurately classified...
Typically, lymphatic tissue proliferative lesions include either benign lesions or lymphoma. However, not all lymphatic lesions can currently be accurately classified into one category, particularly in mucosal areas that are in contact with the external environment. To explore the morphology, immunophenotype, and molecular changes of Non-neoplastic B-cell predominant lymphoid proliferations (NBPLP) in pathological areas that are exposed to external surroundings which mimicked lymphoma. 18 cases of Atypical lymphoid hyperplasia (AtLP) were retrieved in this study. The biopsy samples were mucosal samples obtained from areas exposed to external surroundings, including intestines, urethra, cervix, tonsils, and tongue. Microscopically, there is a different level of B cell hyperplasia accompanied by morphological atypia. We categorized the morphology into 4 groups: type A (7/18), type B (3/18), type C (3/18), type D (5/18). Part of the AtLP was found positive for BCR gene rearrangement (6/15), and TCR gene rearrangement (1/4). The follow-up period ranged from 14.2 to 70 months. No evidence of lymphoma was found. Therefore, we diagnosed all of the presented cases as NBPLP. We illustrated the key differential points and provided valuable diagnostic experience on each subtype. Areas exposed to the external environment are commonly exposed to antigen and easily present with AtLP of NBPLP, accompanying with positive IGH rearrangement. Therefore, a comprehensive evaluation of macroscopic, morphology, immunophenotype, and molecular diagnostics is required to prevent the overdiagnosis of lymphoma.
Topics: Humans; Female; Middle Aged; Male; B-Lymphocytes; Lymphoma; Diagnosis, Differential; Adult; Aged; Cell Proliferation; Immunophenotyping
PubMed: 38886178
DOI: 10.1177/03946320241264369