Parathyroid Adenoma With Respiratory-Like Epithelium: Case Report of a Potential Mimic With Unknown Etiology

Parathyroid adenoma is a tumor composed of increased parenchymal tissue, often built-up by chief cells, transitional cells or oncocytic cells arranged in acinar or solid formations. Occasionally, rare histological patterns are reported, including cystic or trabecular arrangements. We present a 47 year-old male patient with primary hyperparathyroidism who underwent focused parathyroidectomy for a right inferior adenoma. Surgery was uneventful, but histologically, normal parathyroid tissue adjacent to a tumorous structure displaying a cystic growth pattern was detected. The cells lining the cyst walls appeared cylindrical and pseudo-stratified, vaguely reminiscent of a respiratory type of epithelium usually associated to branchial cleft cysts or thyroglossal cyst remnants, albeit with a tumorous appearance. The respiratory-like epithelium stained positive for parathyroid markers PTH and GATA3, thereby confirming them as parathyroid-derived. The patient was cured from surgery as he displayed normal calcium and PTH levels postoperatively, and is currently alive and well without signs of relapse 4 years after surgery. This is to our knowledge the first report of a parathyroid tumor displaying a respiratory-like epithelium. Experimentally, canine parathyroid glands can develop ciliated respiratory epithelium in response to inhalation of ozone. Our patient is a construction worker with a hypothetically increased risk of continuous ozone exposure. Although this association remains purely speculative, future investigations of this tumor phenotype could perhaps yield novel insights regarding the frequency of this histological variant, potential clinical associations, and clues regarding influencing factors.

Rectal metastasis from bladder urothelial carcinoma: a case report

Background Urothelial carcinoma arises from transitional cells in the urothelial tract. In advanced cases, it can metastasize locally to surrounding organs or distally to organs such as the lungs, bones, or liver. Here we describe a case of rectal metastasis from urothelial carcinoma treated with multiple sessions of transurethral resection of bladder tumor (TURBT). Case presentation A 72-year-old woman presented to our department with abdominal bloating andobstructed defecation. She had undergone two sessions of TURBT for early urothelial carcinoma in another hospital at 64 and 65 months ago, respectively. Cystoscopy at 3 months after the second TURBT session had indicated disease recurrence, and thus, she had been referred to our hospital for further examination, followed by TURBT for the third time at 59 months ago and for the fourth time at 48 months ago; thereafter, she had been followed up with cystoscopy every 6 months without any recurrence. However, she returned to our hospital, complaining of difficult defecation. Subsequent colonoscopy demonstrated an obstructive tumor in the rectum, which was pathologically diagnosed as metastatic urothelial carcinoma of the bladder. Laparoscopic examination revealed two small areas of peritoneal dissemination in the pelvis. A sigmoid colostomy was performed without rectal tumor resection. She has been receiving chemotherapy and is still alive 10 months after surgery. Conclusions Rectal metastasis is a rare site of metastasis for urothelial carcinomas. It is important to consider the possibility of annular rectal constriction caused by infiltrating or metastasizing urothelial carcinoma when managing patients with urothelial carcinoma and with difficult defecation.

Ineffectual AEC1 differentiation from KRT8hi transitional state without fibrosis is associated with fatal COVID-19 ARDS

COVID-19 ARDS is associated with prolonged ventilator dependence and high mortality, but the underlying mechanisms are unknown. Critical to the pathogenesis of ARDS is injury to the alveolar epithelial cell (AEC) barrier; clinical recovery requires epithelial regeneration. We previously identified a KRT8hi transitional state that regenerating AEC2s adopt during differentiation into AEC1s, the persistence of which may be pathogenic in pulmonary fibrosis. Here, we hypothesize that ineffectual differentiation of transitional cells into AEC1s without fibrosis may perpetuate barrier permeability and poor clinical outcomes in COVID-19 ARDS. To test this hypothesis, we examined postmortem lung tissue of COVID-19 ARDS patients. We observed extensive AEC1 injury, rare mature AEC2s, and abundant transitional cells. Transitional cells were cuboidal, partially spread or, rarely, flat but did not express AEC1 markers. They formed monolayers on alveolar septa denuded of AEC1s but structurally normal without fibrosis. We conclude that ineffectual AEC1 differentiation from transitional AECs may perpetuate barrier permeability and respiratory failure in COVID-19 ARDS. In contrast to fibrosis, transitional AECs may retain the capacity for physiologic AEC1 regeneration with restoration of normal alveolar architecture and function. Novel therapies to promote AEC1 differentiation from transitional cells may accelerate barrier restitution and clinical recovery in ARDS.

Fate mapping quantifies the dynamics of B cell development and activation throughout life

SummaryFollicular mature (FM) and germinal centre (GC) B cells underpin humoral immunity but the dynamics of their generation and maintenance are not clearly defined. Here we exploited a fate-mapping system in mice that tracks B cells as they develop into peripheral subsets, together with a cell division fate reporter mouse and mathematical models. We find that FM cells are kinetically homogeneous, recirculate freely, continually replenished from transitional populations, and self-renew rarely. In contrast, GC B cell lineages persist for weeks with rapid turnover and site-specific dynamics. Those in the spleen derive from transitional cells and are kinetically homogeneous, while those in lymph nodes derive from FM B cells and comprise both transient and persistent clones. These differences likely derive from the nature of antigen exposure at the different sites. Our integrative approach also reveals how the host environment drives cell-extrinsic, age-related changes in B cell homeostasis.

NEPHRECTOMY BY PAPILAR CARCINOMA OF TRANSITIONAL CELLS (UROTELIAL) HIGH GRADE NOT INVASIVE CASE STUDY

Cancer is one of the main causes of morbidity and mortality worldwide, it is produced by the transformation of normal cells into tumor cells in a multiple stages process that can progress to a precancerous lesion to a malignant tumor that can spread through the blood and lymphatic system causing metastasis. The incidence of kidney cancer seems to be increasing, in adults, it begins in the kidneys and can spread to the entire urinary tract that surrounds distant organs or places, renal cell carcinoma is the most common type of kidney cancer and represents approximately 90 percent of cancers tumors. The present study evidences the case of a patient who comes to medical services when the problem shows symptoms. Objective - To describe the renal cancer case of a patient with papillary transitional cell carcinoma who was operated to remove a kidney tumor in order to prevent it from triggering in severe states. Method - The literature on cancer and cancer patients has been reviewed, in the urinary system the data of a case that generated kidney tumor surgery performed in a 63-year-old female patient has been reviewed. Result - High-grade, non-invasive papillary transitional cell carcinoma (UROTELIAL) can occur, in patients altering the quality of life of people, if it is detected and treated in time complications can be avoided Conclusion - It is essential to identify the risk factors and possible causes that can trigger this type of pathology, the information collected is expected to be useful to professionals and to contribute as an alert to detect health problems in patients early.

Subpopulations of blood monocytes in patients with generalized hypoxia

The aimof the work is to establish general regularities and features of differentiation of blood monocytes into 4 subpopulations in diseases associated with circulatory and respiratory hypoxia.Materials and methods.18 patients with ischemic heart disease (IHD), 12 patients with ischemic cardiomyopathy (ICMP), 14 patients with chronic obstructive pulmonary disease (COPD), 15 patients with newly diagnosed infiltrative pulmonary tuberculosis (PTB) and 12 healthy donors were examined. In whole blood, we determined the relative number of different subpopulations of monocytes by flow cytometry. The results were analyzed by statistical methods.Results.It is shown that an increase in the number of classical (80.56 [77.60; 83.55]%) and the deficit of intermediate (10.38 [9.36; 11.26]%), non-classical (6.03 [5.24; 6.77]%) and transitional (2.14 [1.41; 3.92] %) monocytes in the blood is determined in patients with COPD when compared with the group of healthy donors (p< 0.05). In groups of patients with PTB and IHD, an increase in the number of intermediate monocytes (26.24 respectively [22.38; 42.88] % and 25.27 [15.78; 31.39]%) and the lack of transitional cells (1.77 [1.36; 3.74]% and 2.68 [2.63; 4.0]%) at the normal content of classical and non-classical forms of monocytes (p< 0.05) is detected. In patients with ICMP, a decrease in the number of non-classical monocytes (up to 5.05 [4.08; 6.58]%) is combined with the normal cell content of other subpopulations (p< 0.05). The interrelation between the number of classical and intermediate monocytes in patients with COPD (r= –0.63;p< 0.05), PTB (r= –0.72;p< 0.01), IHD (r= –0.59;p< 0.05), ICMP (r= –0.58;p< 0.05) was established.Conclusion.In COPD associated with generalized hypoxia, an increase in the number of classical monocytes is combined with a deficiency of their other subpopulations in the blood. In PTB and IHD, antigenic stimulation of the immune system mediates accelerated differentiation of monocytes from classical to intermediate forms with a decrease in the number of transitional cells regardless of the etiology of the disease (infectious or non-infectious) and the type of hypoxia (respiratory or circulatory).

Semisoft clustering of single-cell data

Motivated by the dynamics of development, in which cells of recognizable types, or pure cell types, transition into other types over time, we propose a method of semisoft clustering that can classify both pure and intermediate cell types from data on gene expression from individual cells. Called semisoft clustering with pure cells (SOUP), this algorithm reveals the clustering structure for both pure cells and transitional cells with soft memberships. SOUP involves a two-step process: Identify the set of pure cells and then estimate a membership matrix. To find pure cells, SOUP uses the special block structure in the expression similarity matrix. Once pure cells are identified, they provide the key information from which the membership matrix can be computed. By modeling cells as a continuous mixture of K discrete types we obtain more parsimonious results than obtained with standard clustering algorithms. Moreover, using soft membership estimates of cell type cluster centers leads to better estimates of developmental trajectories. The strong performance of SOUP is documented via simulation studies, which show its robustness to violations of modeling assumptions. The advantages of SOUP are illustrated by analyses of two independent datasets of gene expression from a large number of cells from fetal brain.

Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex

Smooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Canonically, smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with features of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.

Organizational Hierarchy and Structural Diversity of Microvascular Pericytes in Adult Mouse Cortex

ABSTRACTSmooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with mixed phenotype of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3-D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.