Sage Open Pathology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 disease, has become an international pandemic with numerous casualties. It had been noted that the severity of the COVID-19 disease course depends on several clinical, laboratory, and radiological factors. This has led to risk scoring systems in various populations such as in China, but similar risk scoring systems based on the American veteran population are sparse, particularly with the vulnerable Veteran population. As a simple risk scoring system would be very useful, we propose a simple Jhala Risk Scoring System (JRSS) to assess the severity of disease risk.

A retrospective review of all SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) tests collected and performed at the regional Veterans Administration Medical Center (VAMC) serving the Philadelphia and surrounding areas from March 17th, 2020 to May 20th, 2020. Data was collected and analyzed in the same year. These tests were reviewed within the computerized medical record system for demographic, medical history, laboratory test history, and clinical course. Information from the medical records were then scored based on the criteria of the Jhala Risk Scoring System (JRSS).

The JRSS, based on age, ethnicity, presence of any lung disease, presence of cardiovascular disease, smoking history, and diabetes history with laboratory parameters correlated and predicted (with statistical significance) which patients would be hospitalized.

The JRSS may play a role in informing which COVID-19 positive patients in the emergency room/urgent care for risk stratification.

Invasive Breast carcinoma—No special type (NST) is the most common breast malignancy accounting for 95% of breast cancers. Study of predictive and prognostic immunohistochemical markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2neu) expression are crucial for treatment planning.

In the present study we studied the hormonal profile in 303 sporadic breast cancers and BRCA1 protein expression in these patients along with its clinico-pathological correlation.

In our patient population, Triple negative Breast carcinoma (TNBC) (104/303; 34.3%) was the most common luminal subtype followed by Luminal A 74/303; 24.4%), Her2 enriched (65/303; 21.5%), and Luminal B (60/303; 19.8%) respectively. This contrasts with many western studies which commonly report Luminal A being the largest subgroup. BRCA1 protein loss was more prominently seen in TNBC (64/104;61.5%) highlighting the possibility that high grade tumors are more susceptible to some epigenetic modifications leading to higher likelihood of loss of BRCA1 protein.

Hence, we conclude that like hereditary cases of breast carcinoma with BRCA1 mutation; BRCA1 loss is also more likely in sporadic TNBC cases.

Early diagnosis of sepsis and its severity is essential for appropriate treatment to improve patient survival, especially in resource-limited settings. The aim of the present study was to study the role of red blood cell distribution (RDW) as a biomarker for the early detection of severe sepsis defined clinically and also in the prediction of mortality from sepsis.

The cross-sectional study included a total of 175 subjects who met the inclusion criteria for the diagnosis of severe sepsis. After a thorough clinical examination, blood samples were taken from all patients within 3 hours of presenting the disease. The RDW values and other investigations were studied on the day of admission compared to other severity markers with the mortality index of 30 days.

The RDW value was significantly higher in patients with severe sepsis and in non-survivor patients than in survivors (P < .0001). There was a strong correlation between the SOFA score and RDW in predicting the disease outcome with the Pearson correlation coefficient of r = .46. The area under the receiver operating characteristic curve was found to be 0.852 at a CI of 95% (0.796-0.909) with RDW 17.15, sensitivity was 88.6% and specificity was 63.5%. There was a positive correlation with Pearson’s correlation coefficient of r = .46 between RDW and the SOFA score.

RDW can be used as a potential marker for the early detection of severe sepsis and in the prediction of the outcome. Large multicenter prospective studies can confirm the utility of this routinely available marker for patients with sepsis.

Intrahepatic cholangiocarcinoma is a highly malignant tumor with a very short 5-year survival. Multistep carcinogenesis has been suggested as the main pathway for the development of this tumor. Main suggested precursors have been (1) biliary intraepithelial neoplasia (BilIN) and (2) intraductal papillary neoplasm of bile duct (IPNB). The former is flat and does not produce grossly and radiologically detectable mass lesion, but the latter produces grossly identifiable lesion.

The development of bile duct dysplasia (BilIN) in chronic biliary diseases has been investigated and proved, but the incidence of BilIN in non-biliary causes of cirrhosis such as hepatitis B and non-alcoholic steatohepatitis has very rarely been investigated. In this study, we have tried to find out the prevalence of BilIN in non-biliary cirrhosis.

During the study period (2017-2018) in 100 explanted livers with the diagnosis of non-biliary cirrhosis, thorough sampling (at least 20 sections) was performed, and pathologic sections were studied for the presence of BilIN.

In the 100 studied livers with different diagnoses of non-biliary causes of cirrhosis, 31% of cases showed BilIN-1 and 2% of cases showed BiliIN-2. No case of BilIN-3 has been identified.

Non-biliary causes of cirrhosis should be considered as precursors of cholangiocarcinoma (BilIN); however, the incidence of this occurrence is low.

The study was conducted to assess the association of neutrophil lymphocyte ratio (NLR) in COVID-19 and to identify the cut-off value that predicts mortality, need of respiratory support and admission to high-dependency or intensive care.

A retrospective observational study was conducted to collect demographic data, clinical variables, the neutrophil-lymphocyte ratio on-admission and the outcome of confirmed COVID-19 patients admitted to a tertiary care center in Sri Lanka.

There were 208 patients with a median age of 56 years (IQR 43-67) and 98 (47.1%) males. The median neutrophil count was 4.07 × 10³/µL (IQR 2.97-6.79) and the median lymphocyte count was 1.74 × 10³/µL (IQR 1.36-4.75). The calculated NLR ranged from 0.12 to 48.28 with a median value of 2.32 (IQR 1.37-4.76). A NLR value >3.6 predicted development of severe disease requiring respiratory support, transfer to a high-dependency or an intensive care unit and/or succumbing to the illness with a sensitivity 80% and specificity 80% (area under the curve 0.8, 95% CI 0.72-0.88, P < .0001). The adjusted odds ratio of NLR > 3.6 on predicting severe disease was 11.1, 95% CI 4.5- 27.0, P < .0001.

A NLR > 3.6 is a useful variable to be included in risk prediction scores in Sri Lanka.

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic disorders. Some clinical manifestations are present at birth, while some develop during childhood, and others can occur at any age. Given the early age at which patients develop clinical features, diagnosis is often made during childhood. The most prevalent features of NF1 are café au lait spots, dermal and plexiform neurofibromas, and learning disability. A variety of skeletal problems may be seen in NF1, including scoliosis, short stature, and pseudoarthrosis. Reduced skeletal bone mass has been documented to be a common phenomenon in children and adults with NF1. Decreased serum 25-hydroxyvitamin D (vitamin D) levels have been noted in adults and children with NF1 and have been reported to be inversely correlated with the number of dermal neurofibromas in adults. However, the actual correlation of vitamin D level to bone density and dermal neurofibroma number in children with NF1 remains unclear.

The primary objective of this study was to evaluate vitamin D levels among children and adolescents with NF1. The secondary objective was to describe the levels of vitamin D among children and adolescents with NF1, to verify in which age group there is a higher frequency of vitamin D alterations, and to explore vitamin D level correlations between age, gender, sun exposure, number of neurofibromas, and number of plexiform neurofibromas.

This was an observational, cross-sectional, hospital-based study. We obtained a convenience sample of individuals with confirmed diagnosis of NF1 from patients attending the Medical Genetics Service of the IPPMG-UFRJ and Santa Casa de Misericórdia of Rio de Janeiro over a 24-month period. We evaluated vitamin D levels in blood samples of patients with NF1 by a chemiluminescent immunoassay method, and we correlated the results with gender, age, number of neurofibromas, number of plexiform neurofibromas, and satisfactory sun exposure.

Of the 55 patients, 28 (50.9%) were female and 27 (49.1%) were male. Patient ages ranged from a minimum of 1.2 to a maximum of 19.6 years (mean age 10.95 years) and the median was 11.11 years. Median and mean body mass index (BMI; z score) were -0.09 (minimum value -1.63 and maximum of 4.62) and 0.16, respectively. The mean value of vitamin D was 30.82 ng/mL (±12.31) and the median was 29 ng/mL (minimum value of 10.40 ng/mL and maximum of 79.19 ng/mL).

The levels of vitamin D did not differ according to gender, age group, or the presence or number of cutaneous neurofibromas. Among patients with adequate sun exposure, there was a higher incidence of sufficient serum vitamin D levels. Patients with cutaneous neurofibromas in the 0 to 11 age group had a greater tendency to vitamin D sufficiency in relation to patients aged 11 to 19 years.

The objectives of this study were the evaluation of pathological characteristics of patients with obesity or metabolic syndrome (MS) as basic cause of death, associating the autopsy findings with some clinical aspects and the abdominal adipose panicle thickness.

A total of 88 autopsy cases were studied, divided into 2 groups based on the main cause of death: group 1 (n = 15) obesity and group 2 (n = 73) MS. Clinical summaries of autopsy requests, macroscopic findings, and histologic sections were reviewed.

The definition of obesity as the basic cause of death is associated with larger thickness of the abdominal adipose panicle, being 8.5 cm (P = .001) the best measurement, according to the receiver operating characteristic curve. Hypertensive cardiopathy (P = .001), ischemic cardiopathy (P = .003), coronary (P = .008)/systemic (P = .005) atherosclerosis, and arterial (P = .014)/arteriolar (P = .027) nephrosclerosis are associated with the diagnosis of MS. Steatohepatitis is associated with the diagnosis of obesity (P = .030); however, its association with the thickness of the abdominal adipose panicle is not statistically significant (P = .211).

In the context of an obese patient in autopsy, pathologist may use the information about abdominal adipose panicle associated with heart, kidney, and liver findings, even macroscopic ones, to decide the basic cause death between obesity and MS.

Histologic subtyping of lung cancer has significant implications for treatment planning. Accurate diagnosis based on cytology/small biopsy specimens is challenging and frequently determined by morphology, as material is often not sufficient for immunohistochemical studies (IHC). We investigated the concordance between the rates of diagnosis from cytology/small biopsies compared with surgical specimens in patients with squamous cell lung cancer (SCC) and the utility of IHC for diagnostic precision in lung cancer subtyping.

We conducted a 5-year retrospective analysis identifying cases of SCC diagnosed on cytology/small biopsies ± IHC and compared them with subsequent surgical specimens when available. The number of patients with SCC on surgical biopsy and the concordance between cytology ± IHC was determined.

Over the 5-year period (2011-2015), 231 cases were identified. Surgery was performed on 66 cases (28.5%), of which 87.9% concurred with cytological diagnosis (95% exact binomial confidence interval [CI] = 77.5%-94.6%). There were 36 cases diagnosed in 2014 and 2015 with IHC data. Of those cytology cases with IHC (n = 12), SCC was confirmed by surgery in 91.7% (95% CI = 61.5%-99.8%). Of those without IHC (n = 24), 95.8% were confirmed SCC by surgery (95% CI = 78.9%-99.9%). These rates were not different (Fisher exact test). All cases with IHC were morphologically squamous.

Our data demonstrate that diagnostic precision of identifying SCC by cytology/small biopsy is comparable with or without additional IHC studies. We recommend judicious use of IHC on cytology specimens, reserving it for cases where cytomorphology is equivocal. Tissue should be preserved for molecular analysis, which may have therapeutic implications.

The most prevalent subtype of non-Hodgkin lymphoma is diffuse large B-cell lymphoma (DLBCL). Germinal center B-cell (GCB) and non-germinal center B-cell (non GCB) are the two main biologically different molecular subtypes identified utilizing an immunohistochemistry-based approach.

Our objective in this study is to analyze the impact of immunohistochemical subtypes of DLBCL (GCB or non GCB) on demographic and clinicopathological parameters, response to chemotherapy and survival outcomes.

This is a retrospective study including 106 cases of DLBCL collected in the department of pathology, Hassan II university hospital, Fez (Morocco), over a period of 12 years (January 2010-September 2022). The subtypes of DLBCLs were defined according to Hans algorithm, using immunohistochemistry by three biomarkers (CD10, BCL6, MUM1).

Independent t tests and analyses of variance were used for the comparison of mean values. We employed the SPSS 26.0 program to achieve this. A statistically significant value was set at P < .05.

Seventy-five patients (71%) were non-GCB subtype, while thirty-one patients (29%) had the GCB immunosubtype. We have found a significant (P < .05) correlations between DLBCL immunosubtypes and treatment responses on one hand and survival in the other hand. In the GCB subtype, the response rate and survival were significantly improved. A significant association was found between Ki 67 expression and survival on univariate analysis. On multivariate analysis, we note a correlation between Ki 67 expression, DLBCL immunohistochemical subtypes and survival outcome.

Non GCB subtype is associated with poor response to treatment and inferior survival outcome compared to GCB subtype in Moroccan context, especially when combined with high expression of Ki 67 marker.

Neurological complications during and after SARS-CoV-2 infection have been frequently described. The detection of either SARS-CoV-2 RNA or specific antibodies against SARS-CoV-2 in cerebrospinal fluid in the context of concomitant neurological manifestations indicates neuroinfection.

This is a retrospective descriptive analysis of cerebrospinal fluids and serum samples from 2 hospitalized patients and autopsy findings from 2 patients who died at home. Samples were analysed by 3 independent enzyme-linked immunosorbent assays. Specific antibodies against SARS-CoV-2 were detected in cerebrospinal fluids and paired serum in all 4 cases. Levels of antibodies in cerebrospinal fluids were highest in samples from a deceased man with critical progression of COVID-19 and detectable SARS-CoV-2 viral RNA in cerebrospinal fluid, serum, 4 brain biopsies and 15 additional tissue samples, though immunohistochemical staining for SARS-CoV-2 in brain tissue did not detect the virus.

Detection of SARS-CoV-2 antibodies in paired serum and cerebrospinal fluid may support the presence of SARS-CoV-2 neuroinflammatory disease in patients with COVID-19 and neurological manifestations.

The Gleason score is an essential tool in the decision to treat localized prostate cancer. However, experienced pathologists can classify Gleason score differently than do low-volume pathologists, and this may affect the treatment decision. This study sought to assess the impact of pathology review of external biopsy specimens from 23 men with a recent diagnosis of localized prostate cancer.

All external biopsy specimens were reviewed at our pathology department. Data were retrospectively collected from scanned charts.

The median patient age was 63 years (range: 46-74 years). All patients had a Karnofsky performance score of 90% to 100%. The median prostate-specific antigen level was 23.6 ng/dL (range: 1.04-13.6 ng/dL). Among the 23 reviews, the Gleason score changed for 8 (35%) patients: 7 upgraded and 1 downgraded. The new Gleason score affected the treatment decision in 5 of 8 cases (62.5%).

This study demonstrates the need for pathology review in patients with localized prostate cancer before treatment because Gleason score can change in more than one-third of patients and can affect treatment decision in almost two-thirds of recategorized patients.

Despite the efficacy of the COVID-19, the search for improvements in the management of severe/critical cases continues to be important. The aim is to demonstrate the kinetics of 4 serological markers in patients with COVID-19 who evolved in hypoxemia.

From June to December 2020, the Health Secretariat of Rondônia State, Brazil, established a home medical care service team (HMCS) that provided clinical follow-up for health professionals and military personnel with COVID-19. The clinical and laboratory monitoring was individualized at home by a nursing and medical team. In addition to laboratory parameters, C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, and D-dimer levels were periodically taken to monitor the evolution of treatment.

Of 218 patients telemonitored, 48 patients needed special care by the HMCS team due to shortness of breath. Chest tomography showed multiple ground-glass shadows and lung parenchymal condensations that was compatible with secondary bacterial infection associated with leukocytosis, for which antibiotics were prescribed. The symptoms were accompanied by increases of CRP and IL-6 levels followed by fibrinogen after a few days, for which an anticoagulant therapy was included. Thirty-three patients evolved to improvements in clinical signs and laboratory results. Between the sixth and eighth day of illness, 15 patients presented signs of hypoxemia with low O₂ saturation accompanied with an increase in the respiratory rate, with some of them requiring oxygen therapy. As they did not present signs of clinical severity, but their laboratory markers showed an abrupt IL-6 peak that was higher than the increase in CRP and a new alteration in fibrinogen levels, they received a supplemental dose of anticoagulant and a high dose of corticosteroids, which resulted in clinical improvement.

Our study demonstrates that monitoring of IL-6 and CRP may identify precocious hypoxemia in COVID-19 patients and prevented the progressive deterioration of the lung injury.