Histological findings in skeletal muscle of SARS-CoV2 infected patient.

Autopsies represent medical procedures through which the causes of patients' deaths are determined or, through tissue sampling and microscopic examination of slides in usual stains or special tests, one can offer the basis for understanding the physiopathological mechanisms that contribute to the patients' death Histological findings of tissue samples from patients who have died of COVID-19 have been mainly orientated to lung, heart, liver, kidney damage with a small percent of them following other organs, but none has, to our knowledge, studied skeletal muscle.

Neuroimmune cross-talk in Helicobacter pylori infection: analysis of substance P and vasoactive intestinal peptide expression in gastric enteric nervous system.

It is suggested that different neuropeptides are actively involved in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis acting as important effectors of the neuroimmune complex interactions, but the available data is limited and contradictory. The aim of this study was to determine whether the chronic infection generates changes in substance P (SP) and vasoactive intestinal peptide (VIP) gastric level and to evaluate the dependence of these potential effects on the degree of bacterial colonization or the severity of the inflammatory infiltrate. Therefore, immunohistochemical tests were performed to examine SP and VIP expression in mucosal nerve endings and myenteric neurons. Both SP and VIP levels were significantly higher in gastric samples of patients infected with H. pylori compared to uninfected individuals, confirming that these neuropeptides are neuroimmune modulators involved in the pathogenesis of H. pylori infection. Although their expression did not correlate with the intensity of mucosal inflammation nor with the bacterial density, we observed a strong association between SP neuronal level and the degree of myenteric ganglionitis, which in turn correlated with the severity of mucosal T-cell infiltration. These findings suggest that the mechanisms of neuroimmune cross-talk depend on some other factors that remain to be determined.

Microbiologic Safety of the Transareolar Approach in Breast Augmentation.

BACKGROUND: In aesthetic breast augmentation, especially by the transareolar approach, there is increasing concern regarding the occurrence of capsular contracture and its potential correlation with intraoperative implant contamination from putative endogenous breast flora of the nipple and lactiferous ducts. However, detectable bacteria cannot be considered synonymous with established resident microflora. OBJECTIVES: The authors sought to elucidate the existence of endogenous breast flora and assess the microbiologic safety of transareolar breast augmentation. METHODS: In this prospective study (BREAST-MF), the authors collected microbiologic samples from the breast skin, ductal tissue, and parenchyma of 39 consecutive female patients who underwent breast procedures in a plastic surgery clinic. Swabs collected pre-, intra-, and postoperatively were processed for bacterial and fungal growth. Positive cultures underwent identification through VITEK and MALDI-TOF, as well as antimicrobial susceptibility testing. RESULTS: Staphylococcus species accounted for 95 of 106 (89.6%) positive results from native breast skin, 15 of 18 (83.3%) positive results from decontaminated breast skin, and 4 of 4 (100%) positive results from the breast parenchyma. Methicillin resistance was present in 26.4% of S. epidermidis, 25.3% of S. hominis, and 71.4% of S. haemolyticus strains. CONCLUSIONS: During transareolar breast augmentation, in the nipple-areola region it is more likely to find bacteria populating the skin, rather than endogenous breast flora, as previously considered. Appropriate preoperative decontamination is essential for minimizing the risk of postoperative infections. LEVEL OF EVIDENCE 3: Risk.

Direct immunofluorescence on hair follicles--present and future perspectives.

Direct immunofluorescence (DIF) is an important tool for evaluating bullous autoimmune and connective tissue disorders. We report 21 cases of pemphigus vulgaris, bullous pemphigoid and lupus erythematosus that were investigated by performing DIF on scalp hair follicles. The study was done using a simplified technique of preparing the hairs for DIF testing. The anagen hairs tested positive in pemphigus vulgaris patients while the telogen hairs were negative. In bullous pemphigoid and lupus erythematosus cases hair DIF presented negative results.Hair DIF has the potential of taking the place of skin or mucosal DIF in pemphigus patients if performed on anagen hair follicles. The technique used to perform hair DIF is important in obtaining reliable results and eliminating the possibility of generating false-negative testing. Larger studies are needed in order to validate this method.

Role of Myokines in Myositis Pathogenesis and Their Potential to be New Therapeutic Targets in Idiopathic Inflammatory Myopathies.

Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases whose treatment is often a challenge. Many patients, even after immunosuppressive therapy, do not respond to treatment, so new alternatives have been sought for this. Therefore, other signaling pathways that could contribute to the pathogenesis of myositis have been investigated, such as the expression of myokines in skeletal muscle in response to the inflammatory process. In this review, we will refer to these muscle cytokines that are overexpressed or downregulated in skeletal muscle in patients with various forms of IIM, thus being able to contribute to the maintenance of the autoimmune process. Some muscle cytokines, through their antagonistic action, may be a helpful contributor to the disease modulation, and thus, they could represent personalized treatment targets. Here, we consider the main myokines involved in the pathogenesis of myositis, expressing our view on the possibility of using them as potential therapeutic targets: interleukins IL-6, IL-15, and IL-18; chemokines CXCL10, CCL2, CCL3, CCL4, CCL5, and CCL20; myostatin; follistatin; decorin; osteonectin; and insulin-like 6. An interesting topic regarding the complex connection between myokines and noninflammatory pathways implied in IIM has also been briefly described, because it is an important scientific approach to the pathogenesis of IIM and can be a therapeutic alternative to be considered, especially for the patients who do not respond to immunosuppressive treatment.

Dangerous Liaison: Helicobacter pylori, Ganglionitis, and Myenteric Gastric Neurons: A Histopathological Study.

Chronic inflammation induced by Helicobacter pylori (H. pylori) infection plays a major role in development of gastric cancer. However, recent findings suggested that progression of inflammation and neoplastic transformation in H. pylori infection are more complex than previously believed and could involve different factors that modulate gastric microenvironment and influence host-pathogen interaction. Among these factors, gastric myenteric plexus and its potential adaptive changes in H. pylori infection received little attention. This study is aimed at identifying the impact of H. pylori-associated gastritis on number and morphology of nerve cells in the stomach. The distribution of density, inflammation, and programmed cell death in neurons was immunohistochemically assessed in full-thickness archival tissue samples obtained from 40 patients with H. pylori infection who underwent surgery for gastric cancer and were compared with findings on samples collected from 40 age- and sex-matched subjects without bacteria. Overall, significant differences were noted between H. pylori-positive and H. pylori-negative patients. The analysis of tissue specimens obtained from those with infection revealed higher density and larger surface of the myenteric nervous plexus, as well as a significant increase in the number of gastric neuronal cell bodies and glial cells compared to controls. A predominant CD3-immunoreactive T cell infiltrate confined to the myenteric plexus was observed in infected subjects. The presence of mature B lymphocytes, plasma cells, and eosinophils was also noted, but to a lesser extent, within the ganglia. Myenteric ganglionitis was associated with degeneration and neuronal loss. Our results represent the first histopathological evidence supporting the hypothesis that H. pylori-induced gastric inflammation may induce morphological changes in myenteric gastric ganglia. These findings could help gain understanding of some still unclear aspects of pathogenesis of H. pylori infection, with the possibility of having broader implications for gastric cancer progression.

Tumor Microenvironment in Diffuse Large B-Cell Lymphoma: Role and Prognosis.

Diffuse large B-cell lymphoma (DLBCL) represents 30-40% of all non-Hodgkin lymphomas (NHL) and is a disease with an aggressive behavior. Because about one-third of DLBCL patients will be refractory or resistant to standard therapy, several studies focused on identification of new individual prognostic and risk stratification biomarkers and new potential therapeutic targets. In contrast to other types of cancers like carcinomas, where tumor microenvironment was widely investigated, its role in DLBCL pathogenesis and patient survival is still poorly understood, although few studies had promising results. The composition of TME and its interaction with neoplastic cells may explain the role of several genes (beta2-microglobulin gene, CD58 gene), receptor-like programmed cell death-1 (PD-1) and its ligand (PD-L1), or other cell components (Treg) in tumor evasion of immune surveillance, resulting in tumor progression. Also, it was found that "gene expression profile" of the microenvironmental cells, the phenotype of tumor-associated macrophages (TAM), the expression of matricellular proteins like SPARC and fibronectin, the overexpression of several types of matrix metalloproteinases (MMPs) like MMP-2 and MMP-9, or the tissue inhibitors of matrix metalloproteinases (TIMPs) may lead to a favorable or adverse outcome. With this review, we try to highlight the influence of microenvironment components over lymphoid clone progression and their prognostic impact in DLBCL patients.

Practical Aspects Regarding the Histopathological Diagnosis of Early Mycosis Fungoides.

Mycosis fungoides is the most common primary T-cell lymphoma of skin. The disease has a protean clinical and histological presentation in its early patch and plaque stages, when distinction from mimicking inflammatory dermatoses is difficult. Since no single criterion is specific enough, a reliable diagnosis in early stages requires integration of clinical, histopathological and molecular findings. In skin biopsies, the most helpful histologic features are the detection of atypical lymphocytes in the epidermis with minimal epidermal changes, basal alignment of lymphocytes along dermal-epidermal junction and formation of Pautrier microabscesses. An aberrant immunophenotype of T cells and molecular detection of a clonal T-cell population are factors that could allow a more specific diagnosis. This work recapitulates and discusses these features from a practical perspective.

Correlations Between the Autolytic Changes and Postmortem Interval in Refrigerated Cadavers.

INTRODUCTION: In forensic pathology the autolytic process has been observed and documented in order to determine the postmortem interval as accurately as possible. The observation and experiments have been carried out on cadavers exposed to environmental conditions - heat, humidity, air currents, soil, water. METHODS: For this study hematoxylin and eosin (HE) stained sections of organ samples from 30 autopsied bodies were examined under the microscope. Modifications of tissue and cell structures were noted in correlation with the bodies' time spent in the Morgue's mortuary refrigerator until the autopsy was performed, which varied between 24 hours and 22 days. RESULTS: All the organs sampled (lung, heart, liver and pancreas) showed severe autolytic alterations after 5 to 8 days. The most heavily affected was the pancreas, cells within Langherhans islets becoming complete autolyzed at the 36 hours mark. Inside organs, autolytic processes occur at different rates depending on the locations within that organ -deeply or superficial; in the heart after 4 or more days subendocardic myocardium shows less severe autolytic changes than the subepicardial one. CONCLUSION: Autolytic processes have a delayed onset and a much lower progression rate in a cold controlled environment. Different organs suffer different rates of autolysis in correlation to their structure and enzymatic content.

Correlations Between the Density of Tryptase Positive Mast Cells (DMCT) and that of New Blood Vessels (CD105+) in Patients with Gastric Cancer.

Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells) and CD 105 (for new vessels). Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement.

Variations in the expression of TIMP1, TIMP2 and TIMP3 in cutaneous melanoma with regression and their possible function as prognostic predictors.

Regression in melanoma is a frequent biological event of uncertain prognostic value as the lesion exhibits heterogeneous phenotypical features, both at the morphological and immunohistochemical level. In the present study, we examined the expression of tissue inhibitors of metalloproteinases (TIMP1, TIMP2 and TIMP3) in melanoma with regression. We specifically examined the expression levels of these TIMPs in regressed components (RC) and non-regressed components (NRC) of the tumor and compared their expression levels with those in non-regressed melanomas. We found that TIMP1 was overexpressed in the NRC of melanomas with partial regression (PR) compared with the NRC in melanomas with segmental regression (SR) (P=0.011). TIMP2 was overexpressed in the NRC of melanomas with PR compared with the NRC in melanomas with SR (PR/SR, P=0.009); or compared with the NRC in melanomas with simultaneous SR-PR (P=0.002); or compared with melanomas without regression (absence of regression) (P=0.037). Moreover, TIMP3 was overexpressed in the NRC of all melanomas with SR as compared to the RC component (P=0.007). Our findings on the differential expression of TIMP1, TIMP2 and TIMP3 in melanomas with regression support the hypothesis that the morphological differences identified in the melanoma regression spectrum may have a correlation with prognosis. This may explain the controversial findings within the literature concerning the biological and prognostic role of regression in melanoma.

Multiple Histological Subtypes of Dermatofibrosarcoma Protuberans Occurring in the Same Tumor.

Dermatofibrosarcoma protuberans (DFSP) represents a low-grade cutaneous sarcoma which may have different histological aspects, presenting as a fibrosarcomatous, pigmented, juvenile, myxoid, atrophic, sclerosing or myoid lesion. Some of these subtypes may occur isolated or in association with one of the others creating hybrid lesions. We present the case of a 66 years old woman having a 4 cm diameter tumor located on the abdominal wall. Histopathological examination of the resection specimen revealed areas of typical DFSP associated with fibrosarcomatous transformation, myoid and myxoid areas. Also, focally, pleomorphic tumor cells and foreign-body type multinucleated giant cells were observed. Immunostains revealed CD34 positivity in typical DFSP and myxoid areas with negative staining of some of the tumor cells in fibrosarcomatous areas and negative staining of myoid areas. Smooth muscle actin was positive in myoid areas. The nature of myoid fascicles in DFSP is a matter of debate, being uncertain whether these represent a type of tumor differentiation or a reactive myoid proliferation. In this particular case, finding the association of myoid cells with blood vessel walls sustains their reactive nature. We present the morphological aspects of the different areas of the tumor with emphasis on differential diagnostic problems and clinical implications.

Problems of Differential Diagnosis in Melanoma Arising from Blue Naevus.

Melanoma arising from blue naevus is an exceedingly rare variant of melanoma. Most of the cases are located in head and neck area, with scalp the most affected site. This type of melanoma develops on blue naevus or resembles blue naevus, most frequently cellular blue naevus. We present the case of a 52 years old female diagnosed with a pigmented melanoma of the scalp, with maximum tumoral thickness of 6.8 mm and invasion of the hypodermis, highly resembling cellular blue naevus. All criteria of malignancy were present: prominent nuclear pleomorphism, infiltrative pattern, tumoral necrosis, high mitotic rate (11 mitoses/mm2) with atypical mitosis and high Ki67 index. No lymph node or distant metastases were identified at presentation. Because of the rarity of cases, histopathological diagnosis can be difficult, differential diagnosis with blue naevi, atypical blue naevi or metastatic melanoma being the most challenging problems. Prognosis is given by tumoral thickness, frequently being more than 4 mm.

Density of Tryptase-Positive Mast Cells Correlated with the Presence of H. pylori in Gastric Neoplasia.

BACKGROUND: Gastric cancer continues to be a platoon leader of mortality causes. A significant number of recent studies show direct or indirect involvement of mast cells (MC), with a complex role both pro- and anti-tumor growth. AIM: To objectify the correlations between expression of MC and presence of Helicobacter pylori (HP) infection depending on neoplastic nature of the gastric damage. SUBJECTS AND METHODS: The study was carried out on archival samples of gastric wall from 30 patients with gastric cancer versus 30 age and sex-matched subjects with gastric surgery for non-neoplastic diseases. The inclusion criteria for the case group were histologically proven stage T3/T4 malignancies with regional lymph node metastases. For each case of the study group, distribution and number of MC tryptase positive (DMC-TP) were analyzed in five different areas from the same gastrectomy specimen: intratumor area, deep and side tumor invasion front, normal gastric tissue sample 5-10 cm or more distant from the tumor and furthest resection margin. RESULTS: Independently of HP infection, the study recorded a significantly lower value of DMC-TP in male patients. In regions with inflammatory lesions and preneoplastic changes and in control cases with non-gastric neoplasia, the DMC-TP level was higher than controls with HP-related inflammatory pathology, thus removing bacterial etiology from the forefront of MC mobilizing causes. CONCLUSION: The presence of H. pylori infection was not found to cause significant changes in terms of mobilizing mast cells in the gastric wall with advanced tumors, with minimal stage III TNM.

Clinical presentation of a patient with cutis laxa with systemic involvement: a case report.

Cutis laxa (CL) or elastolysis is a rare inherited or acquired connective tissue disorder in which the skin becomes inelastic and hangs loosely in folds (Mitra et al., 2013). The clinical presentation and the type of inheritance show considerable heterogeneity (Shehzad et al., 2010). We aimed to present the atypical case of a young male patient diagnosed at 36-year-old with CL with systemic involvement. The complex medical history, with a suspected but unconfirmed progeria at nine months, repeated lung and urinary infections, complicated inguinoscrotal hernia, prostatic hypertrophy, bilateral entropion, colorectal diverticula and heart failure, suggested a systemic genetic disease, but the absence of family history made the diagnosis of CL difficult. The skin biopsy and the characteristic features discovered during anatomopathological exam made possible the positive and differential diagnosis, creating the link between the various organ involvement and CL diagnosis. Because of the age of our patient, of normal growth and mental development, and negative family history, we suspected an autosomal dominant form of CL with early onset and severe manifestation. Of course, we cannot exclude a recessive form, due to the heterogeneity of this disease.

A review of morphological aspects in dermatofibrosarcoma protuberans with clinicopathological correlations.

Dermatofibrosarcoma protuberans represents a rare malignant neoplasm involving the skin affecting all ages, frequently young adults. It is characterized by high rates of local recurrences after surgery and rare distant metastasis. Clinically it may present as a non-protuberant or a protuberant lesion, having a relative non-specific aspect mimicking a scar, morphea, a benign cyst or other skin tumor. Several clinicopathologic subtypes of dermatofibrosarcoma protuberans have been described: fibrosarcomatous, pigmented, juvenile, myxoid, atrophic, sclerosing and myoid. Among these, the fibrosarcomatous variant stands out as the most aggressive subtype with higher risk of local recurrences and metastasis. All clinicopathologic variants have in common a characteristic microscopic pattern of infiltration into subcutaneous fat. However, this may be present on small areas or unavailable for examination on biopsy fragments. For this reason, the awareness of this variable morphology is essential for establishing a correct diagnosis and performing an optimal treatment.

Functional and morphological alterations induced by Helicobacter pylori infection in gastric nerve supply.

Helicobacterpylori (HP) infection is the most common cause of many gastric diseases. One of its pathogenic mechanisms involves the production of a wide spectrum of alterations in different components of the gastric enteric nervous system. Changes in neural circuitry encompass structural abnormalities, sensitive and motor function impairment, altered content and release of neurotransmitters, and seem to be related rather to the inflammatory response of gastric wall than to the bacterial colonization. Although gathered data provide new insights into the complex mechanisms underlying the interactions between HP and enteric nervous system, there still are some controversial aspects. Interestingly, it has been suggested that impaired neural activity might have a potential role in gastric carcinogenesis, but this hypothesis requires further investigation. Future studies shall, therefore, elucidate the neuromodulatory influences of Helicobacter pylori infection on the enteric nervous system. A better comprehension on neural changes during HP-induced inflammation could help in identifying new therapeutic options.

Primary penile melanoma.

Primary penile melanomas are exceedingly rare (less than 1% of primary penile cancers), 221 cases being reported to date in PubMed indexed medical literature. More than half of the cases occur on the gland, usually in older people than on cutaneous counterpart and have unfavourable prognosis mainly due to the belated diagnosis. We report the case of a 77 years old male diagnosed with a pigmented ulcerated nodular melanoma of the gland with maximal thickness of 4.5 mm, mitotic index 8 mitoses/mm2 and vascular emboli. No lymph node enlargements or distant metastases were identified at presentation. Six months after the diagnosis the patient was well, free of disease. Clinically, penile melanomas may be mistaken for several lesions such as squamous carcinoma, penile nevi, pyogenic granuloma, Kaposi sarcoma. Histopathologic diagnosis is usually straight forward except for highly pleomorphic tumors; discrimination between primary penile tumor and penile metastatic melanoma is the most delicate problem of differential diagnosis. The treatment is not standardized; surgical wide excision or partial/total penectomy completed with sentinel lymph node biopsy are the most frequent methods of treatment; multi-agent chemotherapy and/or high-dose interferon alpha 2b therapy are recommended for patients with locally un-controllable disease and/or metastases.

Clinical and histopathological studies using fibrin-rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw.

The authors report their experience using platelet-rich fibrin (PRF) therapy for the treatment of ten patients presenting bisphosphonate-related osteonecrosis of the jaw (BRONJ). The aim of our study was to evaluate the effect of this therapy on recurrent BRONJ and to describe the clinical and histopathological/immunohistochemical staining features of PRF treatment. As such, we describe the method we used and report the results observed in the areas treated as well as side effects. The reported results recommend the safety and efficacy of PRF in treatment of BRONJ.

Long-standing ulcerative colitis complicated with mantle-cell lymphoma transformed in diffuse large B cell lymphoma.

Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon and rectum. Its etiology and pathogenesis are incompletely elucidated, although there are many studies concerning these problems. Chronic inflammation and immunosuppressive treatment are risk factors for epithelial and lymphoid malignancies. We present a case of a 39-year-old man who died after a long-standing untreated UC complicated with mantle cell colonic lymphoma and then with transformation towards a high grade diffuse large B cell lymphoma. Multiple colonic biopsies were collected in various moments of the disease. Microscopic and immunohistochemical features are comparatively presented. This case emphasizes the importance of constant surveillance for UC patients and reaffirms the role of multidisciplinary approach in UC management.