Lymphocytic Inflammatory Infiltrate Research Articles

#2182 An unexpected life-threatening cause of kidney failure

Abstract Background and Aims Kidney failure can appear in acute clinical conditions and the cause cannot always be determined, as in approximately 40% of cases that require renal replacement therapy (RRT). In addition, there are other cases in which a patient with persistently low estimated glomerular filtration rate (eGFR) for 3 months is treated with RRT without a primary renal diagnosis. Systemic sclerosis (SSc) is a rare condition that can lead to RRT due to renal ”crisis”. Autopsy studies reveal kidney pathology in approximately 60 percent of patients with SSc. In addition, as many as 50 percent of patients with SSc have markers of kidney disease, as manifested by mild proteinuria, elevated serum creatinine concentration, and/or hypertension. The aim of our paper is to describe a case in which hemodialysis was initiated in emergency setting and the diagnosis was established after that. However clinical course was fatal and the final diagnosis was SSc. Method A 65-year-old male patient was admitted to the Nephrology department with a weight loss of 20 kg in 2 years, depression, low appetite and progressive decline of physical strength. He was previously diagnosed with diabetes mellitus (DM) and high blood pressure (HBP), the ponderal loss being attributed to DM. Insulin treatment was initiated together with antihypertensive medication. In the following 3 months, the kidney function deteriorated progressively and hemodialysis was started. Gray scale and CEUS US were performed to assess a possible cause of kidney failure. However, after the commencement of hemodialysis, the clinical condition did not improve and patient died in respiratory failure complicated by continuous pleural effusion. A skin biopsy from the right thigh was performed for the positive diagnosis. Results At clinical evaluation the patient was cachectic, with striking generalized parchment-like skin lesions which were suggestive both for ichthyosis or SSc. Laboratory tests revealed hyperglycemia, anemia, hypoalbuminemia, increased lactate dehydrogenase and creatine kinase (CK), mild proteinuria and glomerular hematuria. On the other side, myositis antibodies (AB) panel, antinuclear AB, tumor markers for pancreas and gastro-intestinal carcinoma, AB for vasculitis and lupus were negative. Ultrasound (US) (grey scale and CEUS) described dilated bile ducts and gallbladder with massive sludge, without evidence of tumoral neovascularization, and shrunk kidneys with hypoechoic medulla. CT scan confirmed the US findings. Dialysis parameters indicated kt/V 1.4 and urea reduction ratio of 79%. Therefore, no metabolic disturbances could explain the severely altered medical status. The clinical condition of the patient made the kidney biopsy unfeasible. Nevertheless, we decided to perform a skin biopsy, which revealed gross collagen bands, absence of sebaceous glands or hair follicles, as well as rare capillaries with lymphocyte inflammatory infiltrate and absence of hypoderma, thus confirming the diagnosis of SSc. Conclusion SSc can present with obscure clinical signs, leading to multiple organ dysfunction and initially unapparent cause of kidney failure. However, clinicians must be aware of potentially suggestive etiological signs such as parchment-like skin lesions and high blood pressure in a patient with multiple comorbidities. One must differentiate a dehydrated skin from a pathognomonic skin lesion as it is in SSc.

Pathological, morphological, and molecular characterization of the infection by Brachycladium goliath in humpback whale Megaptera novaeangliae.

The humpback whale (Megaptera novaeangliae) is a cosmopolitan migratory, seasonal mysticete that frequents the Brazilian coast. Strands of specimens may occur during the migratory stay in the country. In 2021 and 2022, three live humpback whales stranded on the coast of Rio Grande do Sul and Santa Catarina states in southern Brazil. After euthanasia, specimens were necropsied, and organs were thoroughly examined for lesions. Grossly, in all three cases, the liver exhibited multifocal, irregular, firm, white areas on the hepatic capsule, which extended into the parenchyma. On the cut surface, the livers were yellow to pale brown with orangish to greenish areas, the bile ducts were prominent, thickened, and severely dilated, and leaf-shaped flukes were found inside of them. Additionally, one case showed moderate atrophy of the right hepatic lobe. The histological findings included dilation of bile ducts, hyperplasia of the bile duct epithelium, marked inflammatory infiltration of lymphocytes, plasma cells, and eosinophils, and portal fibrosis. The parasite Brachycladium goliath was both morphologically and molecularly identified based on diagnostic key for trematodes and the original description of the species, and the amplification and sequencing of the ITS-2 region, respectively. Even though hepatic injury was not the primary cause of stranding, it may have contributed to the debilitation of the whales. To the authors' knowledge, this is the first study that reports M. novaeangliae as a definitive host of B. goliath and that describes the lesions caused by the parasite in cetaceans.

Asymptomatic keratotic papules on the lower limbs.

Hyperkeratosis lenticularis perstans (HLP) or Flegel disease is a rare dermatosis of unknown cause, characterized by multiple erythematous hyperkeratotic papules with symmetrical distribution. Treating HLP is challenging because there is no standardized therapy. We describe the case of a 71-year-old light-skinned woman who presented with symmetrical asymptomatic keratotic papules on the dorsal feet, legs, thighs and upper limbs. Histopathological examination showed orthokeratotic hyperkeratosis, hypogranulosis and a band-like inflammatory lymphocytic infiltrate on the dermis, consistent with HLP or Flegel disease.

Clinical Features, Diagnosis, Treatment, and Prognosis of Heparin-Induced Bullous Hemorrhagic Dermatosis

Background. Heparin-induced bullous hemorrhagic dermatosis (HBHD) is a rare cutaneous adverse effect of heparin and has unclear clinical features. We explored the clinical features of HBHD to provide evidence for the safe use of heparin. Methods. We collected HBHD-related case reports for a retrospective analysis by searching the Chinese and English databases from inception to December 31, 2022. Results. Seventy-two patients, including 51 males (70.8%), were included, and they had a median age of 71.5 years (range: 21, 94). Low-molecular-weight heparin was used in 62 patients (86.1%), and unfractionated heparin was used in 10 patients (13.9%). The median time for HBHD to appear was 7 days (range: 0.25, 270). Lesions appeared far from the injection site, and the extremities (57 patients, 79.2%) were the most frequently involved site. The blisters were mainly located in the intraepidermal (34 patients, 47.2%), subcorneal (10 patients, 13.9%), and subepidermal (9 patients, 12.5%) regions. Thirty-seven patients (51.4%) had no obvious dermal inflammatory infiltration, and 20 patients (27.8%) had lymphocytic inflammatory infiltration. Sixty-seven patients (93.1%) recovered from their skin lesions after the discontinuation of heparin or despite continuing heparin and at a median treatment time of 14 days (range: 2, 141). Conclusion. HBHD is a rare self-limiting disease that occurs far from the injection site. Clinicians should be aware of BHD during the administration of heparin. Heparin can be discontinued or continued depending on the patient’s condition.

Clinicopathological Spectrum of Interface Dermatitis

Introduction: Interface dermatitis, which is characterized by variable dermoepidermal interface inflammation and the presence of vacuolar damage to the basal layer, which causes keratinocyte death or necrosis, is a broad term that encompasses many distinct illnesses. . Aim: The present study was planned to correlate the significance of Interface dermatitis with their clinico-pathological aspects. Methodology: This was a retrospective study conducted on 170 cases diagnosed as interface dermatitis over a period of two years. Skin biopsy samples received from the outpatient department were analysed. Results: In the present study, a total of 170 cases were analysed which clinically presented as papulosquamous disorders. On histopathological diagnosis, LP and its variants were the most common type disorder. The most consistent histolopathological characteristic feature noted was basal cell vacuolar degeneration in the epidermis along with a band of lymphocytic inflammatory infiltrate. Clinicopathologic concordance was seen in 86.5% cases. Conclusion: Thus, combination of the histologic details, in correlation with the clinical data helps in arriving at a specific diagnosis of various ID.

Design of an oral vaccine using Lactococcus lactis against brucellosis: an in vitro and in vivo study

Brucellosis is regarded as one of the world’s most severe zoonotic diseases. This study aimed to investigate the possibility of using recombinant Lactococcus lactis (L. lactis) as a live vector to produce recombinant Brucella abortus (B. abortus) Omp10. The gene sequences were obtained from GenBank. The proteins’ immunogenicity was assessed using Vaxijen. After confirming the cloning of the Omp10 gene in the pNZ8148 vector by enzymatic digestion and PCR, transformation into L. lactis was done. SDS-PAGE and western blot methods evaluated omp10 protein expression. Mice received oral recombinant L. lactis vaccines. IgG antibodies against Omp10 were tested using ELISA. Real-time PCR and ELISA were used to analyze cytokine responses. Survival rate and histopathological changes were evaluated after the challenge. Omp10 was chosen for its 1.5524 antigenicity score. Enzymatic digestion and PCR identified a 381-bp gene fragment. A 10 kDa band indicated the success of L. lactis transformation. Mice administered the L. lactis-pNZ8148-Omp10-Usp45 vaccination 14 days after priming showed significantly higher Omp10-specific total IgG and IgG1 (P < 0.001) than the PBS control group. The mice who received the L. lactis-pNZ8148-Omp10-Usp45 and IRBA vaccines had significantly elevated levels of IFN-γ, TNFα, IL-4, and IL-10 in samples collected on days 14 and 28 (P < 0.001). Inflammatory response, morphological damage, alveolar edema, and lymphocyte infiltration were reduced in the target group. A recombinant L. lactis expressing the Omp10 protein was constructed as an oral Lactococcus-based vaccine and compared to live attenuated vaccines for future brucellosis investigations.

Clinicopathological Characteristics and Outcome of Cytophagic Histiocytic Panniculitis: A Single-Center, Retrospective Study.

Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis associated with systemic features characterized by the infiltration of subcutaneous adipose tissue by benign-appearing T lymphocytes and phagocytic histiocytes, mimicking hemophagocytic lymphohistiocytosis (HLH) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). To establish the clinicopathological features and response to treatment of CHP and evaluate the prognosis of patients and guide therapy based on the current state of knowledge. Clinical, laboratory, histopathological, and outcome data of 12 patients with CHP were retrospectively collected between 2009 and 2022. All the patients presented with plaques or nodules, mostly located in the lower extremities (11/12). Fewer cases involved systemic symptoms (9/12) and laboratory abnormalities (6/12), and none were positive for serum Epstein-Barr virus (EBV)-DNA. Histopathological examination revealed mixed septal and lobular inflammatory infiltration of histiocytes and lymphocytes. Large or atypical lymphocytes were rarely present (2/12). In some patients, varying proportions of plasma cells, neutrophils, and eosinophils were observed. The extent of histocytophagy was mild (9/12), moderate (2/12), and severe (1/12). HLH was not observed in any of our cases, none of which were fatal. The uniqueness of our study lies in the presence of neutrophil-rich dermal and subcutaneous infiltrates, associated with connective tissue disorders (CTD) and streptococcal infections. Our study reveals that EBV-negative CHP tends to a better prognosis than previously research, filling the gap in the much-needed details of CHP in the Chinese population. Moreover, CHP may present as a reactive process in combined primary diseases; further studies are required to validate these findings.

Profile and immune environment of upper tract urothelial carcinoma

Upper Tract Urothelial Carcinoma (UTUC) are tumors that share similarities with bladder tumors. Immunotherapy is already used for bladder locations and appears to have interest for UTUC. In order to rationalize the immunotherapy development pipeline it seemed necessary to describe the immune infiltrate of a cohort of UTUC treated with nephroureterectomy and to determine the expression of a panel of immune checkpoints and co-stimulatory molecules on tumor cells as well as on infiltrating and circulating lymphocytes. This is a monocentric, prospective and exploratory work. Patients treated with total nephroureterectomy or segmental ureterectomy for presumably infiltrative (≥T1) UTUC managed at the Saint-Louis Hospital were included from January 2019 to July 2020. A set of markers and immune checkpoints were studied by flow fluorocytometry on circulating lymphocytes (PBMCs) and tumor-infiltrating lymphocytes (TILs). Some markers were also studied by immunohistochemistry on tumor sample. In total, 14 patients were included and 13 patients could be analyzed. 1 patient had no residual tumor. 5 tumors out of the 12 (41.7%) showed a lymphocytic inflammatory infiltrate. PD1 was the most represented checkpoint with a median expression rate of 41.4% on CD4+ TILs and 3.89% on circulating CD4+ T cells. This rate was 62.4% and 7.45% respectively on CD8+ T cells. TIGIT was the second most represented marker with a median expression rate on tumor-infiltrating CD4+ T cells of 25% and 2.9% on circulating CD4+ T cells. The median expression level of TIGIT on tumor-infiltrating CD8+ T cells was 23.3% and 3.2% on circulating CD8+ T cells. ICOS was highly expressed on CD4+ TILS with a median of 33.9% in contrast to CD8+ TILS (median: 6.67%). Variable expression of other checkpoints (ILT2, TIM3, LAG3 and OX40) was found without clear trend. This exploratory work highlighted that PD1 was the most represented checkpoint. TIGIT was the second most represented checkpoint while ICOS, TIM3 and LAG3 were 3 other checkpoints whose expression was found to be less important. ILT2 and OX40 appeared to be weakly expressed. II.

Ex vivo imaging of subacute myocardial ischemia with ultra-short echo time 3-D quantitative T1-mapping MRI in mice

Abstract Introduction Cardiac magnetic resonance (CMR) is important tool for assessment of structure and function of the myocardium in various cardiac conditions, such as after myocardial infarction (MI). CMR methods rely solely on multi-slice 2-D imaging, which tends to be slow, since every slice is imaged separately with the &amp;gt;3 min scan time. Furthermore, multi-slice methods are somewhat approximate, due to the slice thickness, which is usually around 1 mm for mice and 8 mm for humans. Therefore, 3-D CMR imaging methods with isotropic resolution are urgently needed. In this study, we present quantitative, ultra-short echo time 3-D Look-Locker T1[1] Multi-Band SWeep Imaging with Fourier Transform[2] and Compressed Sensing[3] (LL MB-SWIFT-CS) technique for imaging in MI mice hearts ex vivo. Purpose To develop an ultra-short echo time 3-D CMR method for imaging subacute myocardial ischemia quantitatively and in an accelerated way. Materials and Methods Hearts were collected 7 days after Left Anterior Descending (LAD) Coronary Artery was ligated in C57BL mice, fixated in 4% PFA in PBS and imaged with LL MB-SWIFT-CS MRI. The heart was scanned in 3-D with a total acquisition time of 3.25 min with resolution of 256³. For T1 determination, saturation recovery (SR) of the longitudinal magnetization was measured with following parameters: TR=3 ms, FA=4º, FOV=25 mm³, total number of unique spokes acquired=16384 and spokes per LL curve=1024, filling the 3-D data space homogeneously 16 times during the recovery. Total scan time was 52 min. After imaging, the SR LL curve was reconstructed into 32 images with CS reconstruction. For comparison, we imaged the hearts with 2-D MRI TRAFF2-mapping method[4] and histology. For regions of interests (ROIs) analysis, the damaged and remote ROI areas were observed from 2-D MR images and drawn to corresponding anatomical 3-D images. The same ROIs were then used to collect the T1 relaxation time data. For histology, standard paraffin embedding, and tissue processing protocols were used. 4 μm thick sections were cut and stained with Hematoxylin Eosin and Sirius Red staining. Results and Discussion The T1 relaxation time values were elevated in the damaged areas (p&amp;lt;0.005) (Fig. 1), as shown earlier[5,6]. The T1 values in the ischemic and remote myocardium were 0.76±0.03s and 0.70±0.02s, respectively. Ischemic areas can also be observed visually in the T1- and 2D TRAFF2-maps (Fig. 2). Sirius Red staining showed increased collagen formation in the ischemic myocardium, supporting the CMR findings. Moreover, hematoxylin-eosin staining showed loss of cardiomyocytes and coronary capillaries, and infiltration of inflammatory cells, like macrophages and lymphocytes. Conclusion With this method, we were able to detect the statistically significant differences between damaged and remote tissue based on the T1-relaxation times within the myocardium, allowing isotropic quantitative 3-D assessment of the entire myocardium.T1 values for MB-SWIFT-CSVisual validation of MB-SWIFT-CS

Immunization of BALB/c mice with BAB1-0278: An initial investigation of a novel potential vaccine for brucellosis based on Lactococcus Lactis vector

The gram-negative intracellular bacterium Brucella abortus causes bovine brucellosis, a zoonotic disease that costs a lot of money. This work developed a vector vaccine against brucellosis utilizing recombinant L. lactis expressing Brucella outer membrane protein BAB1-0278. Gene sequences were obtained from GenBank. The proteins' immunogenicity was tested with Vaxijen. The target vector was converted into L. lactis after enzymatic digestion and PCR validated the BAB1-0278 gene cloning in the pNZ8148 vector. The target protein was extracted using a Ni-NTA column and confirmed using SDS-PAGE and western blot. After vaccination with the target vaccine, the expression of IgG subclasses was evaluated by the ELISA method. Cytokine production was also measured by the qPCR method in the small intestine and spleen. Lymphocyte proliferation and innate immune response (NLR, CRP, and PLR) were also assessed. Finally, after the challenge test, the spleen tissue was examined by H&E staining. BAB1-0278 was chosen because of its antigenicity score of 0.5614. A 237-bp gene fragment was discovered using enzymatic digestion and PCR. The presence of a 13 kDa protein band was confirmed by SDS-PAGE and western blot. In comparison to the PBS group, mice given the L. lactis-pNZ8148-BAB1-0278-Usp45 vaccine 14 days after priming had substantially greater levels of total IgG, IgG1, and IgG2a (P < 0.001). Also, the production of cytokines (IFN-γ, TNFα, IL-4, and IL-10) indicating cellular immunity increased compared to the control group (P < 0.001). The target group had a lower inflammatory response, morphological impairment, alveolar edema, and lymphocyte infiltration. An efficient probiotic-based oral brucellosis vaccination was created. These studies have proven that the recommended immunization gives the best protection, which supports its promotion.

Pathological findings in autoimmune encephalitis autopsy specimens from cases of suspected prion disease.

The underlying pathology of autoimmune encephalitis is not well characterized due to the limited opportunities to study tissue specimens. Autopsy specimens available at prion surveillance centers from patients with suspected Creutzfeldt-Jakob disease offer a unique opportunity to study the pathology of autoimmune encephalitis. Our objective was to describe pathological findings of autoimmune encephalitis specimens submitted to the U.S. National Prion Disease Pathology Surveillance Center. Pathology reports were obtained from the National Prion Center. Specimens negative for prion disease were screened for inflammatory pathology and those suggestive of autoimmune encephalitis were analyzed. Cases identified on autopsy were compared to institutional cases with fatal seronegative autoimmune encephalitis and available brain biopsy. Between 1998 and 2022, 7934 specimens were evaluated of which 2998 (38%) were negative for prion protein. Querying the database for alternative diagnoses of encephalitis/encephalopathy yielded 43 cases that were screened by an experienced neuropathologist yielding 14 (0.5%) cases consistent with autoimmune encephalitis. Most specimens showed diffuse inflammation involving the limbic system (86%), basal ganglia (86%), cortex (71%), diencephalon (71%), and in some cases the brainstem (43%) and cerebellum (43%). Lymphocytic inflammatory infiltrate was predominantly perivascular with parenchymal extension in 64%. Microglial activation/nodules were seen in 64% of cases. Neuronal loss was present only in 50%. Pathological findings were identical to biopsy specimens from our institutional cohort. Seronegative AE may have consistent pathology with diffuse or multifocal perivascular inflammation and microglial activation. Half the patients do not have neuronal loss suggesting a potential for neurological recovery. These findings are preliminary and require further confirmation.

Pembrolizumab-induced erosive lichenoid reaction in a patient with metastatic lung adenocarcinoma: A case report

Introduction: Immune-related adverse events induced by immune checkpoint inhibitors are quite common. Cutaneous lichenoid immune-related adverse events are among the most frequent. However, oral lichenoid adverse reactions are extremely rare. We herein describe a patient who was treated with pembrolizumab for metastatic lung cancer and developed an erosive oral lichenoid reaction induced by immunotherapy. Case presentation: An 87-year-old man treated with pembrolizumab for metastatic lung adenocarcinoma (stage IVa based on AJCC 2018) developed multifocal erosions of the oral mucosa mainly located on the buccal mucosa, palate, and inner portion of the lips with multiple small, irregular, hyperkeratotic areas. Histopathological examination showed epithelial necrosis and a dense band-like layer of an inflammatory infiltrate of lymphocytes and histiocytes within the upper dermis. Direct immunofluorescence was negative for both IgG and C3. A diagnosis of erosive oral lichenoid reaction of the mucosa induced by immunotherapy was established. Given the severity of the condition, pembrolizumab treatment was withheld and concomitant topical and systemic steroids were started. After 1 month, the drug-related toxicity was ameliorated and immunotherapy was re-introduced. Discussion: Only one other case of pembrolizumab-induced erosive lichen planus of the oral mucosa has been described to date. Previously reported drug-induced lichenoid rashes were mainly localized on the skin. Clinically, the main differential diagnoses of lichenoid erosive lesions are bullous immune-related disorders and should be excluded. In our patient, histological examination combined with negative results of both direct immunofluorescence and enzyme-linked immunosorbent assays confirmed the diagnosis of erosive lichenoid drug reaction. Conclusion: Clinicians should be aware of lichenoid involvement of the oral mucosa because related pain and food intake difficulties may seriously compromise treatment compliance. Prompt treatment of oral drug-related reactions may prevent interruption of immunotherapy and improve patients’ quality of life.

Novel patch biomaterial treatment for colon diverticulosis in swine model.

Current leading managements for diverticular disease cannot prevent the recurrence of diverticulitis, bleeding and/or other complications. There is an immediate need for developing new minimal invasive therapeutic strategies to prevent and treat this disease. Through a biomechanical analysis of porcine colon with diverticular lesions, we proposed a novel adhesive patch concept aiming at mechanical reconstruction of the diseased colon wall. This study aims to evaluate the surgical feasibility (safety and efficacy) of pulmonary visceral pleura (PVP) patch therapy using a pig model of diverticulosis. Six female Yucatan miniature pigs underwent collagenase injection (CI) for the development of diverticular lesions. The lesions in each animal either received patch implantation (treated group, n = 40 for 6 pigs) or left intact (untreated group, n = 44 for 6 pigs). The normal colonic wall in each animal received patch implantation at two spots to serve as control (n = 12 for 6 pigs). After 3months of observation, the performance and safety of the patch treatment were evaluated through macroscopic and histological examination. We found that 95% of pouch-like herniation of the mucosa was prevented from the colon wall with the treatment. The pouch diameter was significantly reduced in the treated group as compared to the untreated group (p < 0.001). The patch application caused a significant increase in the levels of collagen of the colon tissue as compared to the untreated and control groups (p < 0.001). No difference was found in the lymphocyte and macrophage inflammatory infiltrate between the groups. Our results suggest that patch treatment efficiently inhibits the diverticular pouch deformation and promotes the healing of the colon wall with a normal inflammatory response, which may minimize the risk of diverticulosis reoccurrence and complications over time.

Cytotoxicity, biocompatibility and osteoinductive profile of an MTA-hydrogel-based cement: An in vitro and animal study.

This study aimed to evaluate the cytotoxicity, biocompatibility and osteoinductive profile of a mineral trioxide aggregate (MTA)-hydrogel-based material (MTA Flow) in comparison with MTA Angelus. Cell viability was evaluated in human periodontal ligament stem cells (hPDLSCs) using the methyl-thiazol-tetrazolium (MTT) colourimetric assay. Polyethylene tubes containing the tested materials and empty polyethylene tubes (control) were implanted in the subcutaneous tissue of Wistar rats. Cellular (lymphocyte infiltration) and extracellular events (ECM; collagen fibres) were analysed in histological sections. Immunohistochemical (collagen I, osteopontin, bone sialoprotein, bone morphogenetic protein4) analyses were also performed. At 24, 48 and 72 h, all tested groups showed cell viability similar to control (p > .05). Regarding biocompatibility, all groups showed similar cellular events represented by a slight inflammatory reaction characterized by hyperaemia and a mild lymphocytic inflammatory infiltrate. The analysis of lymphocytes during the time showed a decrease in these cells in the control group and a significant interaction between MTA Angelus and control (p < .001), with MTA Angelus showing a more extensive inflammatory infiltrate. Regarding fibres, an increase in content was observed in all groups during the experimental time (7, 30 and 60 days), however, no difference was detected among the experimental groups (p = .063). After 60 days, the immunoexpression of bone matrix proteins in the MTA Flow group was similar to or higher than that observed in the MTA Angelus and in the control group. MTA Flow showed a non-cytotoxic behaviour, biocompatibility and ability to stimulate tissue mineralization.

T-cell Lymphoma in the Nasal Cavity in Goat

Background: Lymphomas are considered uncommon in goats, being the multicentric form with the highest number of cases for the species. Primary intranasal lymphomas are often diagnosed in dogs, cats, and humans. In the literature, there is only a description of a multicentric case involving the frontal sinuses and mucosa of the nasal cavity in a goat; therefore, it is important to describe unusual cases of this disease for the inclusion of new clinical and pathological characteristics in the ruminant clinic medicine. The objective of this work is to describe a case of T-cell lymphoma in the nasal cavity of a young goat.Case: The animal had dyspnea and respiratory noise for 15 days. Clinical examination showed nodulation in the right nasal cavity associated with serosanguinous secretion. Tracheostomy was performed; however, after 30 days the animal was euthanized. A sagittal plane of the head showed a pinkish-gray mass in the right and left nasal cavity, with a smooth, multilobulated surface, smooth adhering to the rostral portion of the dorsal concha and occluding the dorsal nasal meatus. Submandibular lymph nodes were slightly enlarged. Histopathological examination of the nasal cavity revealed a non-encapsulated, poorly delimited and ulcerated tumor composed of round cells arranged in a mantle supported by a discrete fibrovascular stroma extending the mucosa and lamina propria. Cells were round with sparse, eosinophilic and poorly delimited cytoplasm. Nuclei varied from round to elongated with condensed chromatin and evident nucleoli. Occasionally, aberrant nuclei, reniform shape and multinucleated cells were seen. Pleomorphism was moderate characterized by anisocytosis and anisocariosis. Typical and atypical mitosis were frequent (0-4 per field of highest magnification [400x]). Amidst the neoplasm, there were multifocal areas of necrosis and hemorrhage associated with a mild lymphocytic inflammatory infiltrate. Immunohistochemistry showed positive immunostaining for Vimentin antibodies and CD3, and negative for pan CK and CD20.Discussion: The lymphomas immunophenotyping is little used when it comes to farm animals, and there are few studies that use this technique for the definitive diagnosis of these neoplasms for small ruminants. The use of this technique must be considered in each case, in order to determine the pathogenesis, the accurate diagnosis and the origin of the neoplastic lymphocytes. In goats, T-cell lymphomas are the most diagnosed, although cases of multicentric B-cell lymphomas with ocular involvement have been diagnosed. In view of the clinical picture of the case described, infectious rhinitis already described in goats, such as aspergillosis and protothecosis, should be included as differential diagnoses. However, the anatomopathological findings facilitate the direction of the diagnosis, since infectious rhinitis presents as nodules / ulcerated masses or focal areas of necrosis associated with purulent secretion and in the histopathological examination it is possible to observe the intralesional etiological agents. In addition, the enzootic ethmoidal tumor must be included, as it has similar clinical signs and affects young animals, but they are adenomas/adenocarcinomas that affect the ethmoidal nasal shells induced by a retrovirus. Lymphomas in the caprine species are rare in the Northeastern semi-arid, but that in the present diagnostic routine occasionally occurs, being important the first description of its nasal shape for its inclusion in the differential diagnoses of diseases that present with clinical obstruction and dyspnea for the species. Keywords: hematopoietic neoplasia, immunophenotyping, lymphocytes, dyspnea.Descritores: neoplasia hematopoietica, imunofenotipagem, linfócitos, dispneia.Título: Linfoma de células T na cavidade nasal de caprino.

Mycobacterial Spindle Cell Pseudotumor of the Nasal Cavity.

Mycobacterial spindle cell pseudotumor (MSCP) represents an uncommon tumor-like proliferation associated with nontuberculous mycobacterial infection, i.e., M. avium intracellulare, affecting primarily the lymph nodes of immunocompromised men in their 5th decade. Involvement of the nasal cavity by MSCP is exceedingly rare with only 3 well-documented examples in the literature. A 74-year-old, HIV-negative, man presented with a 0.5-cm nodule of the left nasal cavity clinically presenting as a "nasal polyp." His medical history was significant for colonic adenocarcinoma, cutaneous basal cell carcinoma, and chronic lymphocytic leukemia (CLL) transforming to B-cell prolymphocytic leukemia, responsive to chemotherapy. The patient was diagnosed with prostatic adenocarcinoma treated with radiotherapy two months before the nasal lesion was detected. No lymph node enlargement, pulmonary involvement or hepatosplenomegaly were noticed. The nasal nodule was surgically excised and histopathologically examined to rule out metastatic disease or CLL relapse. Microscopically, the lesion comprised a well-circumscribed, monotonous, spindle cell population in a vaguely storiform arrangement mixed with a heavy infiltrate of neutrophils and sparse lymphocytes. The spindle cells featured finely granular rich eosinophilic cytoplasm with rounded, oval to epithelioid, or elongated nuclei with vesicular chromatin and one or two distinct nucleoli. The lesional cells lacked overt cytologic atypia and showed occasional regular mitoses. The surface epithelium was intact or focally ulcerated. By immunohistochemistry, the spindle cell population stained strongly and diffusely for CD68 and was negative for AE1/AE3, SMA, CD34, and PSA. CD3 highlighted scattered lymphocytes. Ziehl-Neelsen stain disclosed numerous intracytoplasmic acid-fast bacilli. A diagnosis of MSCP was rendered. No recurrences were observed during a 24-month follow-up period. Although exceptionally rare, MSCP should be considered in the differential diagnosis of nodular lesions of the nasal cavity that are characterized microscopically by marked spindle cell proliferation in a vague storiform pattern, admixed with a lymphocytic or mixed inflammatory infiltrate. A negative medical history for HIV infection and medication-induced immunosuppression should not preclude a diagnosis of MSCP, particularly in extranodal sites. Once the diagnosis is established, prognosis appears to be excellent for nasal MSCP following conservative surgical excision.

Inflammatory myofibroblastic tumor of the lung involving the central nervous system in pediatric patients

The inflammatory myofibroblastic tumor (IMT) is a very rare lesion with an incidence of less than 0.1% of total neoplasms and with main affection in the lungs. Involvement in the central nervous system is extremely rare, but with a much more aggressive course than IMT diagnosed in the rest of the body. We report the 2 cases presented in our neurosurgery department to date; both were treated satisfactorily without intercurrences in 10years of follow-up. The World Health Organization described the IMT as a distinctive lesion composed of myofibroblastic spindle cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils. Clinical manifestations of patients with CNS IMT vary and may consist of headache, vomiting, seizures, and blindness. Seizures are the most common symptom in patients with focal lesions. The true origin of this entity remains to be elucidated, but to date, etiologies ranging from chromosomal alterations to autoimmune or postinfectious mechanisms have been described. Due to its rarity and non-specificity in imaging, the final diagnosis of IMT in the brain parenchyma relies on pathological examination. Treatment options are controversial and include total or subtotal removal, high-dose steroids, and radiation therapy. In the last decade, the development of ALK Tyrosine Kinase Inhibitors allows the possibility of chemotherapy in those patients harboring ALK mutations. IMT is a rare tumor that can exceptionally be found in the CNS. The cause is still unknown although the different studies focus on a neoplastic origin. The diagnosis is based in the use of different modalities of imaging and with histological confirmation. Optimal management is gross total resection whenever possible, is the only established curative treatment. Further research with longer follow-up is needed to clarify the natural history of this rare tumor.

Dynamics of pathomorphological changes in the liver of rats at different stages of experimental alcohol damage

Liver diseases represent one of the most common problems in gastroenterology. The liver, as the most important organ of metabolism, which plays a major role in anabolic and energy processes, takes part in the adaptive and compensatory reactions of the body under exogenous and endogenous adverse influences. Individual factors play a major role in the development of this disease, one of which is the duration of the effect of alcohol on the body. The duration of alcohol consumption affects the morpho-functional properties of the liver. When alcohol was given to the research animals, hypertrophic changes were seen in the linear dimensions of hepatocytes: in the 12th week of alcoholization, the nuclear area was 1.25 times larger, and the cytoplasmic area of hepatocytes was 1.16 times larger compared with the same indicators in the 6th week of alcoholization. Alcoholic hepatitis is characterized by protein-fatty degeneration, inflammatory lymphocytic infiltration, increase in the area of sinusoids and the size of hepatocytes, and, accordingly, the Vizotto coefficient (1.83 times in the 6th week and 2.10 times in the 12th week of the research). The alcohol consumption is accompanied by increase in the volume of the nucleus and cytoplasm of hepatocytes, decrease in the nuclear-cytoplasmic ratio with increase in pathohistological changes. With the lengthening of the terms of alcoholization, the number of binuclear hepatocytes decreased. Morphometric calculation of the number of fat cells per 100 hepatocytes showed that in the 12th week of the experiment, the number of fatty inclusions increased by 1.42 times, compared with 6 weeks of forced alcoholization. Fatty small- and large-droplet steatosis of hepatocytes was diffuse in nature. The duration of alcoholization also affects the liver vessels. The diameter of the central vein in the 6th week of the experiment was 1.52 times greater than in control rats, and 1.81 times in the 12th week of alcoholization. The bile ducts of rats of the experimental groups were also larger in diameter: by 37% after 6 weeks and 47% after 12 weeks of forced alcoholization. An increase in the area of the sinusoids and the diameter of the central vein indicates an impairment of the blood supply to the liver. The complexity of the structure of the liver and the diversity of its functions necessitate the use of a variety of diagnostic techniques and methodological approaches to assessing its activity in the normal condition, during a pathology. It will be promising to study the structure of the liver at the ultramicroscopic level of the effect of drugs on the treatment of alcoholic liver disease during different periods of alcoholization.

Evaluation of Immunohistochemical Expression of Heparanase in Helicobacter pylori-Associated Chronic Gastritis.

Chronic gastritis (CG) is a very common disease. More than half of the worldwide population suffers from symptoms of CG. This disease has received great attention since the discovery of H. pylori as the most important cause of CG. Symptoms experienced by patients with CG are attributed to H. pylori-induced inflammatory reactions. Heparanase (HPSE) is a mammalian β-endoglucoronidase. In inflammation; HPSE degrades and remodels the extracellular matrix's heparan sulfate polysaccharide chains liberating heparan sulfate-bound cytokines and chemokines, HPSE also facilitates movement of inflammatory cells. This study aimed to detect the function of HPSE in CG by correlating levels of HPSE expression with histopathological features of CG, including H. pylori infection, acute and chronic inflammatory cells, mucosal atrophic and/or metaplastic features. Ninety-five upper endoscopic-guided gastric punch biopsies were enrolled in this study. From each specimen, formalin-fixed and paraffin-embedded tissue blocks were prepared. Tissue sections were stained by Hematoxylin and eosin, Giemsa, and anti-heparanase antibody. HPSE expression was statistically associated with H. pylori infection (P-value < .000), and intensity of chronic lymphocytic inflammatory infiltrate in the gastric mucosal tissues (P = .004). High levels of HPSE expression were also related to the presence of neutrophils in the gastric surface epithelium and lamina propria (P-value < .009). HPSE expression was upregulated in H. pylori-associated chronic gastritis. Thus, future therapeutic agents that could specifically inhibit HPSE enzyme activity, may aid in the reduction of sequelae of H. pylori infection.

Pathological Changes in the Lungs of Patients with a Lethal COVID-19 Clinical Course.

The novel coronavirus SARS-CoV-2 was identified in 2019 and quickly became the cause of the fifth worst pandemic in human history. Our goal for this research paper was to examine the morphology of the lungs in 88 patients that died from COVID-19 in Latvia, thus increasing the data available about the histological characteristics of SARS-CoV-2-induced disease. Lung tissue samples from 88 autopsies were visualized in hematoxylin-eosin and assessed by light microscopy. The male-to-female ratio was 56:32, and the mean age was 62 years ± 15.5 years (22-94 years). Clinically important laboratory data were assessed, including leucocyte count, CRP (C-reactive protein) and D-dimer levels. Signs of diffuse alveolar damage were found in 83/88 (94.3%; 95% CI 87.0-97.9) of patients, 38/88 (43.2%; 95% CI 33.3-53.6) in the exudative phase, and 45/88 (51.1%; 95% CI 40.8-61.3) in the proliferative phase. Vascular damage was identified in 70/88 (79.5%; 95% CI 69.9-86.7) of patients, and 83/88 (94.3%; 95% CI 87.0-97.9) had signs of thrombosis. A sparse inflammatory infiltrate of lymphocytes and macrophages was a common finding aside from cases with an identified coinfection. Eighty patients had significant co-morbidities, including coronary heart disease (49), primary arterial hypertension (41), and diabetes mellitus (34). Since our group's demographic profile and spectrum of co-morbidities were analogous to other reports, the histological findings of marked diffuse alveolar damage, widespread vascular lesions, and active thrombosis can be considered representative of severe COVID-19.