Pathobiology最新文献

Introduction: GATA3 is a transcription factor involved in epithelial cell differentiation. GATA3 immunostaining is used as a diagnostic marker for breast and urothelial cancer but can also occur in other neoplasms.

Methods: To evaluate GATA3 in normal and tumor tissues, a tissue microarray containing 16,557 samples from 131 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

Results: GATA3 positivity was found in 69 different tumor types including 23 types (18%) with at least one strongly positive tumor. Highest positivity rates occurred in noninvasive papillary urothelial carcinoma (92-99%), lobular carcinoma (98%), carcinoma of no special type of the breast (92%), basal cell carcinoma of the skin (97%), invasive urothelial carcinoma (73%), T-cell lymphoma (23%), adenocarcinoma of the salivary gland (16%), squamous cell carcinoma of the skin (16%), and colorectal neuroendocrine carcinoma (12%). In breast cancer, low GATA3 staining was linked to high pT stage (p = 0.03), high BRE grade (p < 0.0001), HER2 overexpression (p = 0.0085), estrogen and progesterone receptor negativity (p < 0.0001 each), and reduced survival (p = 0.03).

Conclusion: Our data demonstrate that GATA3 positivity can occur in various tumor entities. Low levels of GATA3 reflect cancer progression and poor patient prognosis in breast cancer.

The history of pathology involves human dissections, autopsies, microscopy, as well as the development of histopathological, immunohistochemical, and molecular techniques. Through these methods, our understanding of anatomy and disease improved, and models of pathogenesis were gradually refined over time. This review discusses key milestones in the development of pathology as a branch of medical science, from ancient civilizations to the modern day.

Introduction: The extent of spread through air spaces (STAS) is less investigated among patients with lung adenocarcinoma who underwent sublobar resection. Therefore, we aimed to evaluate the extent of STAS semi-quantitatively, to assess its prognostic impact on overall survival (OS) and recurrence-free survival (RFS), and to investigate the reproducibility of this assessment.

Methods: The number of tumour cell clusters and single tumour cells within air spaces was recorded in three different most prominent areas (200x field of view). The extent of STAS was categorized into three groups, and the presence of free tumour cluster (FTC) was recorded.

Results: Sixty-one patients were included. Recurrence was more frequent with higher grade (p = 0.003), presence of lymphovascular invasion (p = 0.027), and presence of STAS of any extent (p = 0.007). In multivariate analysis, presence of FTC (HR: 5.89; 95% CI: 1.63-21.26; p = 0.005) and more pronounced STAS (HR: 7.46; 95% CI: 1.60-34.6; p = 0.01) had adverse impact on OS and RFS, respectively. Concerning reproducibility, excellent agreement was found among STAS parameters (ICC range: 0.92-0.94).

Discussion: More extensive STAS is an unfavourable prognostic factor in adenocarcinomas treated with sublobar resection. As the evaluation of extent of STAS is reproducible, further investigation is required to gather more evidence.

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma commonly associated with B-cell dysregulation. Correlations involving B-cell dysregulation and clinicopathological features remain unclear.

Methods: We prospectively collected blood samples from 11 AITL patients and 17 healthy controls. The percentages of B-cell subpopulations and lymphocytes with IL-21 production were assessed using flow cytometry. Peripheral blood lymphocyte morphology was evaluated microscopically.

Results: Six of 11 (54.5%) patients presented with polyclonal hypergammaglobulinemia. Three of 11 (27.3%) tumor biopsies showed monoclonal immunoglobulin gene rearrangement. The patients exhibited significantly lower levels of naive (p < 0.001) and class-switched (p < 0.001) B cells than controls. The percentages of IgD-CD27- B cells (p = 0.007) and antibody-secreting cells (ASCs) (p = 0.001) were increased. Blood smears revealed atypical lymphocytes and immature plasma cells with morphological diversity. In comparison to normal controls, IL-21 production significantly increased in CD4+ (p < 0.001) and CD8+ (p = 0.020) T cells. B-cell clonality, RHOA G17V mutation, and the presence of sheets of clear cells and immature/mature plasma cells in lymph nodes were significantly associated with percentages of class-switched B cells and ASCs. The patients with circulating EBV DNA had a lower percentage of naive B cells (p = 0.009).

Conclusions: Our results demonstrated a wide spectrum of peripheral B-cell morphologies and immunophenotypes of peripheral B cells in AITL. These findings correspond to dysregulated B-cell immunity and heterogeneous clinicopathological features.

Introduction: Primary effusion lymphoma (PEL) is a malignant lymphomatous effusion, which by definition is Kaposi sarcoma herpesvirus/human herpesvirus 8-positive. PEL typically occurs in HIV-infected patients but can also occur in HIV-negative individuals, including in organ transplant recipients. Tyrosine kinase inhibitors (TKIs) are currently the standard of care for patients with chronic myeloid leukemia (CML), BCR::ABL1-positive. Although TKIs are extremely effective in treating CML, they alter T-cell function by inhibiting peripheral T-cell migration and altering T-cell trafficking and have been associated with the development of pleural effusions.

Case presentation: We report a case of PEL in a young, relatively immunocompetent patient with no history of organ transplant receiving dasatinib for CML, BCR::ABL1-positive.

Discussion: We hypothesize that the loss of T-cell function secondary to TKI therapy (dasatinib) may have resulted in the unchecked cellular proliferation of Kaposi sarcoma herpesvirus (KSHV)-infected cells, leading to the emergence of a PEL. We recommend cytologic investigation and KSHV testing in patients being treated with dasatinib for CML who present with persistent or recurrent effusions.

The incidence, presentation, and predisposing factors of post-acute sequelae of COVID-19 (PASC) are currently poorly understood. Lung explants may provide a rare insight into terminal SARS-CoV-2-associated lung damage and its pathophysiology. A 62-year-old man presented with progressively worsening respiratory symptoms after recovering from mild COVID-19 3 months earlier. No underlying pulmonary comorbidities were reported. A chest CT revealed bilateral extensive ground-glass and reticular opacities, suspicious of pulmonary fibrosis. Despite initial high-dose glucocorticoid therapy, the interstitial lung disease progressed, and after exhausting all viable therapeutic options, bilateral lung transplantation was successfully conducted. Histological analysis revealed extensive end-stage interstitial fibrosis with diffuse dendriform ossification and bronchiolar and transitional cell metaplasia. Signs of interstitial remodeling such as an increased interstitial collagen deposition, a pathological accumulation of CD163+/CD206+ M2-polarized macrophages with an increased expression of phosphorylated ERK, and an increased density of CD105+ newly formed capillaries were observed. qRT-PCR and immunohistochemistry for SARS-CoV-2 N-protein in the endothelium of medium-sized vessels confirmed a persistence of SARS-CoV-2. Our findings highlight a highly unusual presentation of SARS-CoV-2-associated lung fibrosis, implying that incomplete viral clearance in the vascular compartment may play a vital pathophysiological role in the development of PASC.

Introduction: Lobular breast cancer represents 10%-15% of breast cancers in women but is virtually nonexistent in men, related to the typical absence of the anatomic breast lobule structure in male breast tissue. We describe donor-transmitted metastatic lobular carcinoma to a male after kidney transplantation. Determining whether a post-transplant cancer is transplant associated, donor transmitted, or donor derived is significant for treatment, prognosis, and possibly management of other organ recipients.

Case report: A 74-year-old Caucasian male presented to the emergency department with lower abdominal pain and macro-hematuria. Past medical history included two renal transplantations. Computed tomography identified a 4-5-cm space-occupying lesion in the native left kidney. A left native nephrectomy was performed. Histology pathologic examination demonstrated lobular (as opposed to ductal) breast carcinoma. Fluorescent in situ hybridization probes to identify X- and Y-chromosomes showed tumor cells with an XX genotype, whereas the surrounding host cells were of XY genotype. These findings confirmed the female-sex origin (donor) of the tumor within the XY native male (current patient) tissues.

Discussion/conclusion: Due to discordance between the donor and recipient sex, fluorescent in situ hybridization as a molecular technique correctly identified the origin of an individual's cancer in the post-transplant setting. The metastatic breast cancer behaved more indolently than usually seen. Expanded criteria donors (ECD) are those who cannot donate under standard criteria for organ transplantation; expanded criteria widen the potential organ donor pool at the expense of increased risk for post-transplant complications (e.g., graft failure, the transmission of malignancy). The case provides a potential area of future research into considering allowing ECDs with a distant history of cancer with very low transmission risk when the biochemical environment of the recipient would, in the unlikely event of transmission, induce the tumor to pursue an indolent clinical course.

Introduction: The clinical course of prostate cancer (PCa) is highly variable, ranging from indolent behavior to rapid metastatic progression. The Gleason score is widely accepted as the primary histologic assessment tool with significant prognostic value. However, additional biomarkers are required to better stratify patients, particularly those at intermediate risk.

Methods: In this study, we analyzed the expression of 86 cancer hallmark genes in 171 patients with PCa who underwent radical prostatectomy and focused on the outcome of the 137 patients with postoperative R0-PSA0 status.

Results: Low expression of the IGF1 and SRD52A, and high expression of TIMP2, PLAUR, S100A2, and CANX genes were associated with biochemical recurrence (BR), defined as an increase of prostate-specific antigen above 0.2 ng/mL. Furthermore, the analysis of the expression of 462 noncoding RNAs (ncRNA) in a sub-cohort of 39 patients with Gleason score 7 tumors revealed that high levels of expression of the ncRNAs LINC00624, LINC00593, LINC00482, and cd27-AS1 were significantly associated with BR. Our findings provide further evidence for tumor-promoting roles of ncRNAs in PCa patients at intermediate risk. The strong correlation between expression of LINC00624 and KRT8 gene, encoding a well-known cell surface protein present in PCa, further supports a potential contribution of this ncRNA to PCa progression.

Conclusion: While larger and further studies are needed to define the role of these genes/ncRNA in PCa, our findings pave the way toward the identification of a subgroup of patients at intermediate risk who may benefit from adjuvant treatments and new therapeutic agents.

Introduction: End-stage renal disease (ESRD) and acquired cystic kidney disease (ACKD) are known risk factors for renal cell carcinoma (RCC). Hereby, the clinicopathological features of RCCs developed in ESRD were investigated.

Methods: A database consisting of 34 tumors from 31 patients with ESRD among 2,566 nephrectomy samples of RCC was built. The demographic, clinical, and follow-up data along with pathological parameters were analyzed. The RCCs were diagnosed according to the current WHO Classification of Urinary and Male Genital Tumors.

Results: Twenty-two tumors developed in men and 12 in women, with a median age of 56 years (range: 27-75 years). The causes of ESRD were glomerulonephritis (n = 7), hypertensive kidney disease (n = 6), autosomal dominant polycystic kidney disease (n = 6), chronic pyelonephritis (n = 4), diabetic nephropathy (n = 3), chemotherapy-induced nephropathy (n = 1), and undetermined (n = 4). ACKD complicated ESRD in 12 patients. The following histological subtypes were identified: clear cell RCC (n = 19), papillary RCC (n = 5), clear cell papillary tumor (n = 5), ACKD RCC (n = 3), and eosinophilic solid and cystic RCC (n = 2). The median tumor size was 31 mm (range: 10-80 mm), and 32 tumors were confined to the kidney (pT1-pT2). There was no tumor-specific death during the period of this study. Progression was registered in 1 patient.

Conclusion: In our cohort, the most common RCC subtype was clear cell RCC (55%), with a frequency that exceeded international data appreciably (14-25%). The incidence of clear cell papillary tumor and ACKD RCC (14.7% and 8.5%) was lower than data reported in the literature (30% and 40%). Our results indicate a favorable prognosis of RCC in ESRD.