Iranian Journal Of Pathology
Volume:18 Issue: 2, Spring 2023

Mucormycosis (also called black fungus) is an opportunistic serious fungal infection caused by mucormycetes. It can occur in diabetes mellitus patients and other immunosuppressive conditions with recent predisposing factors such as maxillofacial surgery and corticosteroid usage.

In this study, 14 patients were referred to the otorhinolaryngology or ophthalmology ward of Shafa Hospital (Kerman, Iran) with primary symptoms of nasal fullness and Facial nerve dysfunction; they were admitted to the hospital to rule out the fungal infection. An endoscopic biopsy was taken from facial sinuses or orbit, and a microscopic evaluation was performed using hematoxylin and eosin (H&E) and periodic acid–Schiff (PAS) staining methods to rule out mucormycosis.

In the histopathological examination, broad-based nonseptate branching fungal hyphae were found in nasal sinuses through the endoscopic biopsy. Most of the patients had diabetes mellitus with a primary symptom of facial nerve palsy; also, most of them received corticosteroids (intravenous [IV] or intramuscular [IM] injection). All patients have recently been infected with COVID-19 (less than 1 month ago).

COVID-19 infection could play a predisposing factor for many opportunistic infections, such as fungal elements); thus, the physician should be aware of the dose and day of corticosteroid therapy to prevent these infections.

Hepatitis E Virus (HEV) infection may be common in Human Immunodeficiency Virus (HIV-1) patients and may lead to chronic infection as well as cirrhosis. We intended to determine the incidence of HEV infection among HIV-1 patients in comparison to individuals without HIV-1 infection.

In our cross-sectional study, 87 HIV-1-positive patients were compared to 93 healthy individuals in Kerman, Iran. Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from all participants. Plasmas were evaluated for HEV IgM and IgG using the ELISA kit. Then, reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) was used in RNA extractions from PBMCs to check for the presence of HEV RNA.

Among the subjects examined in our study, 61 (70.1%) and 71 (77.4%) out of patients with HIV-1 infection and healthy individuals were male, respectively. The average ages of patients with HIV-1 and the control group were 40.2 years and 39.9 years, respectively. No discernible differences existed between the two groups based on IgM and IgG seropositivity against the HEV. However, HEV-RNA was found in 8% of patients with HIV-1 and 1.1% of HIV-1-negative individuals (P=0.03). There was also an association between the HEV genome and anti-HEV and anti-HCV antibodies in HIV-1-positive patients (P=0.02 and P=0.014, respectively).

HEV infection was more common in HIV-1 patients and may develop a chronic infection in immunocompromised individuals. Here, we suggest molecular-based HEV diagnostic tests, including RT-PCR assays, should be performed in HIV-1 patients with unknown impaired liver function tests.

Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer. Previous studies have elucidated different pathways for the progress of this malignancy. The mutation in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, a member of the MAPK/ERK signaling pathway, plays a role in EOC. The current study aimed to determine the frequency of the BRAF V600E mutation in ovarian serous and mucinous tumors, including borderline and carcinoma subtypes.

A total of 57 formalin-fixed paraffin-embedded samples, including serous borderline tumors (SBTs), low-grade serous carcinomas (LGSCs), high-grade serous carcinomas (HGSCs), mucinous borderline tumors (MBTs), and mucinous carcinomas, and 57 normal ovarian tissues were collected. The BRAF V600E mutation was analyzed using polymerase chain reaction (PCR) and sequencing.

While 40% of the SBT harbor BRAF mutation, we found no BRAF mutation in the invasive serous carcinoma (P=0.017). Also, there was only 1 BRAF mutation in MBT and no mutation in mucinous carcinomas. In addition, we found no mutation in the control group.

The BRAF mutation is most frequent in borderline tumors but not in invasive serous carcinomas. It seems that 2 different pathways exist for the development of ovarian epithelial neoplasms: one for borderline tumors and the other for high-grade invasive carcinomas. Our study supports this hypothesis. The BRAF mutation is rare in mucinous neoplasms.

Lymphovascular tumoral invasion is a typical histopathological feature of gastric carcinomas and supports the recognition of high-risk patients for the recurrence. We aimed to study the CD31 expression in diverse subtypes of gastric carcinomas and to show its association with the histopathologic findings of the carcinoma to assess the prognosis.

This cross-sectional study was conducted on 40 established patients of gastric adenocarcinoma from radical gastrectomy. The patients were classified according to the pathology assessments. Tumoral tissues were assessed by immunohistochemical staining for the CD31 expression. Malignant behavior was estimated by the histopathological evaluations.

CD31 positivity was described in 23 (57.5%) of all evaluated patients. The assessment of CD31 expression and tumor features presented no significant association between the CD31 expression and patients’ age, sex, tumor site,  size, grade and stage, subtypes of carcinoma, perineural invasion, and also lymphovascular invasion (P>0.05).

Lymphovascular invasion makes valuable additional evidence that might be useful to detect gastric carcinoma patients at high risk for the recurrence, who could be candidates for more supplementary therapies. However, in our society, the CD31 expression did not show any association with the aggressive histopathologic features of this tumor.

Patients undergoing neoadjuvant chemotherapy (NC) for invasive breast cancer (IBC) therapy need biomarkers to track their progress. Because of the relationship between NFkB, Survivin, and Cyclin D1 with NC resistance, the different expression levels of each of these biomarkers can be different between pre- and post-NC in IBC. However, no research has examined the correlation between these biomarkers before and after the NC expression. This study aimed to determine the correlation among them.

Biomarkers expression (low and high) was used to classify 30 samples. ER, PR, HER2, Ki-67 status, tumor grade, age, and NC response were assessed. The amounts of Survivin, Cyclin D1, and NFkB were evaluated using immunohistochemistry, and samples were classified based on the cut-off. Chi-square and linear regression were used to evaluate the data.

No significant association was found with the changes in the expression of Survivin, Cyclin D1, and NFkB, both before and after the NC. Significant moderate correlations were shown between before and after the NC Survivin expression (r = 0.513) and Cyclin D1 expression (r = 0.543). The correlation between expression of NFkB before and after the NC was not significant.

The high potential of these proteins as prognostic indicators was demonstrated by the strong positive association between the expression of Survivin and Cyclin D1 before and after the NC. This upregulation of biomarkers indicates chemoresistance in developing IBC in the presence of NC.

The expression of matrix metalloproteinase-9 (MMP-9) and chemokine receptor 7 (CCR7) is significantly associated with tumor invasion and metastasis. Little is known regarding the potential of these markers in predicting cancer metastasis in Laryngeal Squamous Cell Carcinoma (LSCC). Therefore, this study aimed to dissect the potential of these markers in predicting the lymph node metastasis in LSCC patients.

Sixty tissue samples were obtained from the patients diagnosed pathologically with LSCC who underwent partial or total laryngectomy. The expression of MMP-9 and CCR7 was measured using the immunohistochemistry staining in the tissue samples of LSCC patients. The ROC (receiver operating characteristic) curve was used to determine the most significant cut-off points of expression according to the highest sensitivity and specificity of both the markers to predict the lymph node metastasis in LSCC. Then, the relationship between the clinicopathology features and the expression of MMP-9 and CCR7 was evaluated.

The expression of both MMP-9 and CCR7 was significantly correlated with the lymph node metastasis in LSCC (P<0.001). Furthermore, CCR7 expression exhibited the highest prediction accuracy (AUC 95.7%) and sensitivity (100%) in predicting the lymph node metastasis in LSCC compared to that of MMP-9 (AUC 92.9%, sensitivity 90%). We also found that patients with larger tumor size (> 4 cm) had significantly higher expression of MMP-9 and CCR7 (P<0.002 and P<0.001, respectively). The Elevated expression level of CCR7 statistically correlated with higher MMP-9 expression (P<0.001).

MMP-9 and CCR7 might be beneficial as predictors of lymph node metastasis in LSCC patients.

Hepatoblastoma encompasses 1% of pediatric malignancies and is the most common liver malignancy in children. Ninety percent of cases are under 5 years of age. Clinical and pathological risk stratification forms a crucial role in determining the treatment strategy. This study aimed to assess the clinicopathological profile of hepatoblastoma with risk stratification and follow-up in children.

A retrospective evaluation was performed on all pediatric patients recognized with hepatoblastoma between 2016 and 2020 in our institution. Clinical, radiological, biochemical, pathological, and treatment data were analyzed. Cases were stratified based on the SIOPEL protocol and compared with the outcome.

The median age of all children was 1 year, the male-to-female ratio was 2.3:1, and elevated α-fetoprotein (AFP) was observed in all cases. SIOPEL risk stratification showed that 50% of children are at high risk. The histopathological types were fetal (30%), embryonal (20%), and macrotrabecular (5%) patterns under epithelial type and mixed epithelial and mesenchymal type (45%) with 1 case showing teratoid features. During the follow-up period, of the 7 children who died, 6 belonged to the high-risk SIOPEL category, and 5 had a mixed epithelial and mesenchymal pattern.

Our study found a significant correlation between clinicopathological data, histopathological patterns, and outcomes. Accordingly, histopathological patterns could be considered one of the criteria for risk stratification. Histopathological risk stratification indicators (such as SIOPEL and PRETEXT) have strong prognostic and predictive outcomes; hence, our study emphasizes such parameters to aid oncologists.

Endometrial carcinoma is one of the most common malignancies in women in developed countries and the fourth malignancy in Iranian women. Therefore, the identification of its causative factors is essential for the prevention, diagnosis, and treatment. This study was aimed to compare the leptin receptor (Ob-R) expression in the endometrial carcinoma cases and non-carcinoma samples.

In this case-control study, 89 samples (including 45 carcinoma and 44 non-carcinoma samples) were examined. The carcinomatous samples were selected by the census method and others were selected with random method. The data were obtained from histopathologic diagnosis, immunohistochemistry (negative, positive and intensity of immunoreactivity), age, history of diabetes, and hypertension. Ob-R expression was compared in the studied groups using Chi-square, Fisher tests and Multivariate logistic regression analysis. In all tests the level of significance was set at 0.05. The SPSS 26 was used for data analysis.

The frequency of high levels of leptin receptors in the patients with endometrial carcinoma was significantly higher compared to the control group (57.8% vs. 2.3%) (P<0.05). Adjusting the effects of age, history of diabetes mellitus (DM) and hypertension (HTN) revealed that the positive-receptor group had 37.75 (95% CI; 5.18-275.04) odds of having endometrial carcinoma (P<0.001).

The leptin receptor may be a risk factor for the endometrial carcinoma among women tested in Kashan. Based on these results, leptin receptor might be considered as a potential biomarker for screening the endometrial carcinoma or targeting the therapeutic purposes.

Cells of renal cell carcinoma (RCC) are resistant to the most currently used chemotherapeutic agents and targeted therapies; hence, we evaluated the expression of NEK2, JMJD4, and REST in tissues of clear cell renal cell carcinoma (ccRCC) and benign nearby tissues of kidney with the aim of detecting associations between their expression and clinicopathological features, prognostic data, tumor recurrence, and survival rates.

We collected 200 samples from tumor and adjacent non-neoplastic tissues of 100 ccRCC patients. All samples were evaluated for the expression of NEK2, JMJD4, and REST, and the patients were followed up for about 5 years. Tumor recurrence and survival data were collected and analyzed.

NEK2 and JMJD4 expression was increased in ccRCC tissues (P=0.002 and 0.006), while REST was downregulated (P<0.001). The elevated expression of NEK2 was positively related with big tumor size (P=0.015), higher grades (P=0.002), higher stages (P=0.013), distant spread (P=0.004), tumor recurrence, shorter progression-free survival (PFS) rate, and overall survival (OS) rate (P<0.001). Likewise, the high expression of JMJD4 was positively related with big tumor size (P=0.047), higher grades (P=0.003), higher stages (P=0.043), distant spread (P=0.001), tumor recurrence, shorter PFS rate, and OS rate (P<0.001). Conversely, Low expression of REST was positively related to big tumor size, higher grades, higher stages, distant spread, tumor recurrence, and shorter PFS and OS rates (P<0.001).

We demonstrated that overexpression of NEK2 and JMJD4 and downregulation of REST were found in malignant than benign renal tissues and were related to unfavorable pathological findings, poor clinical parameters, and poor patient outcomes.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly frequent malignancy worldwide and is also the leading cause of death. The prognosis for individuals with HNSCC remains dismal, with a five-year survival rate of less than 50%. The novel anti-PD-L1 immunotherapy is found to be promising, and immunohistochemistry (IHC) has been established as a reliable method for patient stratification. We intend to evaluate the prognostic significance of the expression of programmed death ligand-1 (PD-L1) in HNSCC and determine its association with clinicopathological variables.

A total of 50 cases of biopsy-confirmed HNSCC were studied in a tertiary hospital between Dec 2020 and June 2022. The specimens were tested for PD-L1 IHC expression with antibody clone CAL-10 (Biocare) and scored by Combined Positive Score (CPS). The association between PD-L1 expression and clinicopathological variables was evaluated.

PD-L1 was positive in 92% of the cases, and a significant association (P= 0.024) was seen between PD-L1 expression and tumor-infiltrating lymphocytes (TILs). PD-L1 did not show any significant association with patient demographics, tumor site, grade, or stage.

In the present study, evaluation of the immunohistochemical expression of PD-L1 on the tumor cells and TILs in HNSCC revealed a high prevalence of PD-L1 expression. PD-L1 IHC studies for patient selection for immunotherapy would be a promising technique. Frequent PD-L1 expression in tumors with significant TILs may be useful in identifying patients who may benefit from anti-PD-1/PD-L1 therapy.

The prevalence of glomerular diseases, as the leading cause of chronic kidney disease, is increasing. Renal biopsy is still the gold standard for diagnosis of the most kidney disorders. Data on prevalence of the biopsy-proven kidney diseases in Iran is limited and none of the previously reported studies used electron microscopic (EM) evaluation for the diagnosis. This study was conducted to analyze the prevalence of biopsy-proven kidney diseases in a referral center in Iran.

The reports of kidney biopsy samples from 2006 to 2018 referred to a pathology center, affiliated with Tehran University of Medical Sciences were reviewed. The prevalence of different disorders was assessed based on the clinical presentation in 3 age categories, including childhood, adulthood, and elderly.

Among 3455 samples, 2975 were analyzed after excluding transplant-related specimens, suboptimal specimens, and those with uncertain diagnoses. Nephrotic syndrome (NS) (39%) was the most common cause of biopsy followed by subnephrotic proteinuria (18%), hematuria in association with proteinuria (15%), renal failure (9%), isolated hematuria (6%), lupus (4%) and the other non-specific manifestations such as hypertetion or malaise (each one less than 2%). The most common diagnoses included membranous nephropathy (MGN) (17.9%), focal segmental glomerulosclerosis (FSGS) (15.9%), lupus nephritis (LN) (13.7%), minimal histopathological findings (unsampled FSGS versus Minimal Change Disease, 12.1%), Immunoglobulin-A (IgA) nephropathy (6.5%) and Alport syndrome (6.1%). MGN was the most frequent disease before 2013, but FSGS became more frequent after that.

NS and proteinuria were the most indications for kidney biopsy. Although MGN was the most common disease, the prevalence of FSGS has been increasing in recent years and making it the most common disease after 2013. LN and IgA nephropathy are the most common causes of secondary and primary GN presenting with proteinuria and hematuria, respectively.

Tissue microarray (TMA) is a method of harvesting small tissue cores from a number of donor paraffin tissue blocks and arraying them in a recipient paraffin block. It has numerous advantages and applications but is expensive. This study aimed to develop a simple yet efficient method of manual, small-format TMA block construction.

Disposable skin punch biopsy needles were used to manually core out 4-mm cylinders from the archival donor blocks comprising tissue from 60 thyroidectomy specimens. These cores were oriented in the embedding cassette in accordance with the grid design. The molten wax was slowly dispensed and allowed to be set. Sectioning, mounting, and hematoxylin and eosin (H&E) staining were performed by a conventional method. Immunohistochemical studies, using HBME-1, CK19, and S100 antibodies, were also performed on these tissue array sections.

There was no core loss during processing. Technical issues like core tilt and floatation were easily tackled. Morphological identification, histological typing, and immunohistochemical analysis could be satisfactorily performed in these TMA sections. Donor blocks did not break after punching.

This TMA construction method is simple, feasible, easily reproducible, and time-saving. It can serve as an excellent cost-effective alternative for resource-poor laboratories for carrying out immunohistochemical studies.

It was declared that COVID-19 might be more severe in symptomatic pregnant patients. This study was conducted to examine the pathological indices of the placenta in pregnant women who were diagnosed with COVID-19.

A total of 20 COVID-19–positive mothers were enrolled in this study. Detailed placental pathology findings were compared between subjects based on the history of abortion or occurrence of preterm delivery, hypertension, and diabetes.

Intervillositis was the most frequent abnormality of the placenta. There was also a significant association between abortion history and maternal vascular malperfusion (MVM; P=0.02). The placental abnormalities were found to be increased in women with COVID-19, regardless of maternal comorbidities. Further studies are needed to compare the placental pathology between COVID-19–positive women and healthy women.

Placental mesenchymal dysplasia (PMD) is an uncommon placental lesion, which may mimic molar pregnancy at gross and microscopic examination. PMD can be associated with fetal growth restriction, Beckwith-Wiedemann syndrome, intrauterine fetal death, and preterm delivery. Nonetheless, it may also be associated with a normal appearing fetus.

We aimed to emphasize that clinicians, radiologists, and pathologists should be aware of PMD as one of the etiologies of intrauterine growth restriction (IUGR).We presented the case of a 27-year-old gravida 1, para 1 woman who was admitted to Ayatollah Rouhani hospital, in Babol, Iran, at 30 weeks of gestation due to severe IUGR and fetal tachycardia. Ultrasound examination showed uteroplacental insufficiency and increased resistive index (RI) of umbilical artery. At last, a normal female fetus (1320 g) with no definitive anomalies was delivered by cesarean section. Pathological examination revealed cystically dilated stem villi with peripherally located thick-walled muscular stem vessels, and also stromal fibroblasts overgrowth in some stem villi. None of the examined sections revealed trophoblastic proliferation or stromal trophoblastic inclusion. The findings confirmed the diagnosis of PMD.Careful radiological and pathological examination should be performed in the case of IUGR for ruling out the rare placental abnormalities, including PMD.

Angiosarcoma is a malignant vascular tumor that occurs mostly in the soft tissues, skin, trunk, and limbs. Angiosarcoma of the parotid gland is a very uncommon and rare tumor.Herein, we presented a case of a 66-year-old man who was referred for a lump in his neck and his initial biopsy reported Castleman disease. After three months during which the mass did not resolve, a re-biopsy was performed. The biopsy revealed vascular neoplasm composed of neoplastic spindle cells arranged in fascicles with red blood cells between them in the lymph node. This metastatic angiosarcoma was confirmed by immunohistochemical staining. Neoplastic cells were positive for vimentin, EMA, and CD31. The patient underwent radiation therapy. Nine months later, MRI (magnetic resonance imaging) showed a tumor in the parotid gland. The microscopic examination revealed a primary angiosarcoma of the parotid.Although primary angiosarcoma of the parotid gland is very rare, it should be considered as a possible origin in metastatic angiosarcoma of the neck. Further research is recommended on the subject.