Iranian Journal Of Pathology
Volume:16 Issue: 2, Spring 2021

Breast cancer is the most common malignancy in Iranian women and worldwide. Lymphatic vessel invasion (LVI) was found to be an independent prognostic factor in many carcinomas, including invasive carcinoma of the breast. The aim of this study was to compare the hematoxylin and eosin (H&E) staining method and the use of the immunohistochemistry (IHC) marker, D2-40, for evaluating LVI in breast carcinoma specimens.

The study was conducted on 50 patients undergone surgery between the years 2010 and 2015 in Rohani Hospital, Babol, Iran with invasive carcinoma of the breast with Census sampling method. LVI was assessed using H&E staining and two IHC markers, i.e., D2-40 and CD31, by two surgical pathologists.  

LVI was detected in 25 (50%) patients by H&E and in 14 (28%) patients by D2-40. Twelve out of 25 patients with positive LVI in H&E were confirmed by D2-40 and 2 out of 25 patients with negative lymphatic vessel in H&E. Only one case showed weak staining of CD31 proving LVI. These results showed a significant difference between the H&E staining and D2-40 IHC study for LVI detection (p =0.004).

The D2-40 IHC marker is helpful in the diagnosis and confirmation of LVI in invasive carcinoma of the breast. CD31 is not suitable for the evaluation of lymphatic vessels.

CD137 is a member of the TNF-Receptor family. TNF-alpha antagonists have therapeutic effect in active psoriasis. In this study, the relative frequency of CD137 expression was investigated in the inflammatory cells of psoriasis lesions for the first time.

The specimens were obtained from pathology department of Al-Zahra hospital from 2007 to 2016, from paraffin-embedded skin biopsies. A number of 64 psoriasis skin lesions specimens and 34 normal skin specimens were rechecked for the diagnosis. Then, the immunohistochemical staining for CD137, CD4, and CD8 was performed.

CD137 expression of dermal inflammatory cells in psoriasis lesion was 11.19±5.5%. Although, in normal skin biopsied, CD137 expression was observed in 1.3±3.03% of the inflammatory cells. (p =0.001). The relative frequency of the CD137 positive inflammatory cells was significantly more in epidermis versus dermis (epidermis: 31.1%±12.8, dermis 11.1%±5.5). There was no remarkable relation between the CD137 expression rate and the CD4: CD8 ratio.

CD137 as a TNF-alpha receptor has a significant role in pathogenesis of the psoriasis lesions. Therefore, CD137 antagonists can be considered as a novel target for the treatment of incurable psoriasis patients.

Overexpression of human epidermal growth factor receptor 2 (HER2) causes cell transformation and development of various types of malignancies. Idarubicin is an effective anti-neoplastic drug but specific delivery of it to the targeted cells is still a great challenge. Affibody as a cost-effective peptide molecule with low molecular weight has a high affinity for HER2 receptors. Breast and ovarian cancers as wide speared types of malignancies are associated with high expression of HER2. In the current study, we assessed the cytotoxic effects of idarubicin-ZHER2 affibody conjugate on the positive-HER2 cancer cell lines. 

The cytotoxic effects of constructed idarubicin-ZHER2 affibody conjugate on the SK-BR-3, SK-OV-3, and MCF-7 cells with various levels of HER2 expression were evaluated by MTT assay after 48 hours of incubation time.

Idarubicin showed a potent and dose-dependent cytotoxic effect against all treated cell lines while the SK-OV-3 cells were significantly more sensitive. The dimeric form of the ZHER2 affibody molecule showed a mild effect on the cell viability of all treated cells at its optimum concentration. The constructed Idarubicin-ZHER2 affibody conjugate decreased the viability of SK-OV-3 cells at its optimal concentration, more efficiently and specifically than other treated cells. 

The ZHER2-affibody conjugate of idarubicin has a more specific cytotoxic effect compared with idarubicin alone against HER2-overexpressing ovarian cancerous cells. It appears the ZHER2-affibody conjugate of idarubicin has great potential to be implicated as an innovative anti-cancer agent in future clinical trials in patients with HER2-overexpressing ovarian cancer.

Transitional cell carcinoma (TCC) is the world's seventh most common tumor and forms more than 90% of urinary bladder tumors. Invasive tumors have had a poor prognosis, even with surgical treatment and chemotherapy. Some studies have found that an increase of mast cells in TCC is related to the tumor grade and its aggressiveness. This study investigated the relationship between mast cell density (MCD) and features of TCC (tumor stage, grade, prognosis, and recurrence). 

 Materials & Methods:

Fifty-one cases with TCC were selected, and MCD was determined by immunohistochemistry (IHC) and Giemsa staining. Mortality rate and tumor recurrence were recorded.  

The MCD mean was higher in high-grade tumors than in low-grade tumors (in IHC).

  Using mast cell tryptase and Giemsa, MCD has a positive correlation with tumor grade in TCC. Correlations between MCD, recurrence, prognosis, and tumor stage are probably caused by the effect of tumor grade (all with p <0.05).

Glioblastoma is the most common primary malignancy of the brain, the prognosis of which is poor. Immunotherapy with cancer/testis (CT) antigens is a novel therapeutic approach for glioblastoma. This study aimed to investigate the expression rate of MAGE-E1, GAGE, and SOX-6 in glioblastoma tumors using the immunohistochemistry (IHC) method.

Expression of MAGE-E1, GAGE, and SOX-6 were determined by IHC in 50 paraffin blocks of glioblastoma. The results were compared between variables including age, gender, tumor location, and Karnofsky performance status (Kps) score. Survival analysis was also performed.

The expression levels of SOX-6, MAGE-E1, and GAGE were 82%, 78%, and 76%, respectively. The relationship between CT antigens and age, gender, and tumor location was not significant, while the association between MAGE-E1 expression and age was statistically significant (p =0.002). High expression levels of SOX-6 and MAGE-E1 were associated with low Kps scores (p =0.034 and p <0.001, respectively). Survival analysis showed that age >40 and Kps score p =0.005 and p =0.018, respectively). Expression of MAGE-E1 and GAGE was negatively associated with overall 2-year survival (p =0.001 and p =0.021, respectively).

The expression of all the three CT antigens, especially MAGE-E1 and SOX-6, was high in patients with glioblastoma. It can be concluded that these markers are ideal targets for immunotherapy in these patients. MAGE-E1 and SOX-6 can be considered as important markers in determining the prognosis of glioblastoma.

Diagnosis of coronavirus disease 2019 (COVID-19) can be challenging, especially when the real time quantitative reverse transcription polymerase chain reaction (RT-PCR) is not available or it is negative. In this study, we evaluated imaging and laboratory findings in a group of patients with a multidisciplinary diagnosis of COVID-19 pneumonia.

A total of 163 patients with a clinical diagnosis of COVID-19 pneumonia admitted to a specialised respiratory centre in Tehran, Iran were enrolled in this study. The distribution and characteristics of presenting radiological and laboratory findings were evaluated and the relationship to the outcome was investigated.

RT PCR was positive in 92 patients. The diagnosis of COVID-19 in RT-PCR negative patients was made on clinical and radiological grounds (n=71). Also, 24 (14.7%) patients died. The common computed tomography (CT) scan findings included ground-glass (94%) and consolidating opacification (12%), mainly in the lower lobes (90%). Peripheral and central lung changes were observed in 90% and 52% of patients, respectively. Lymphopenia, positive CRP, and raised LDH were present in 32%, 65%, and 96% of cases, respectively. A raised LDH of >500U/L was the best predictor of death in these patients (R2=0.6623; OR=24.4). Other markers of outcome were male gender, age (>50 years), lymphopenia, and severe CXR changes.

Diagnosis of COVID-19 can be challenging, and a multidisciplinary approach is often needed. Whilst RT-PCR is the standard diagnostic test, a negative test should be interpreted with caution. Blood tests and imaging can be useful in the diagnosis, monitoring, and risk assessment in patients with COVID-19.

  Previous studies have addressed the electrolyte abnormalitiessuch as hypocalcemiain COVID-19 patients. We aimed to compare the laboratory findings especially the electrolyte levels amongCOVID-19 patients and healthy controls and evaluate their prognostic values.

This case-control study included 91 COVID-19 patients and 169 healthy individuals. Their laboratory parameters including electrolytes, albumin, liver enzymes, complete blood count, vitamin D, and parathyroid hormone (PTH) were compared. We also analyzed the association between these markers and the major outcomes including severity, mortality and hospitalization.

Among patients with COVID-19, 59.3% of the patients had hypocalcemia on admission while in control group only 32.5% had low calcium level (OR=3.02, 95% CI: 1.79-5.13, p <0.001). The rates of death and ICU admission were significantly higher among the patients in hypocalcemic group than those of eucalcemic group (85.7% vs 14.3% and 33.3% Vs 9.1%, respectively). However, there was no significant difference in the mean PTH and vitamin D levels between the two groups. In terms of the severity of the infection, 74.1% of patients in hypocalcemic group had a severe infection while 24.3% of the patients in eucalcemic group were diagnosed with severe infection (OR=8.89, 95% CI: 3.38-23.37, p <0.001).

Patients with COVID-19 had considerable laboratory abnormalities including hypocalcemia. The hypocalcemia was also associated with worse major clinical outcomes and higher mortality risk.

Urothelial neoplasm (UN) of bladder is a potentially lethal malignancy, particularly in locally advanced or metastatic cases. Development of molecular markers such as HER2 and Survivin may provide useful information on diagnosis and prognosis in UN of bladder.

We studied the immunohistochemical (IHC) expression of HER2 and Survivin in 84 radical/partial cystectomy and transurethral resection (TUR) specimens with different histologic grades and stages.  All samples were obtained from pathology department of Sina Hospital in Tehran, Iran from 2014 to 2018.

From the total number of 84 UN samples, 10 cases (11.9%) had papillary neoplasm of low malignant potential, 30 cases (35.7%) had low-grade papillary urothelial neoplasm, and 44 cases (52.4%) had high-grade papillary urothelial neoplasm. HER2 and Survivin expressions were seen in 44 (52.4%) (p =0.610) and 9 (10.7%) patients (p =0.046), respectively.Survivin expression showed a mild increase in high grade UN.

Our findings suggest that the IHC expression of Survivin and HER2 are not well associated with histological grades of Urothelial neoplasms of bladder. This may be partly due to relatively small sample size and various factors such as patient characteristics or antibody specifications.

Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require accurate subtyping of NSCLCs. There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aimof this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry.

The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values.

SPATS2 and CLCA2were expressed more in LUSC than LUAD. ST6GALNAC1 and Adipophilin were expressed more in LUAD than LUSC (p <0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant differences in survival rates between the patients with negative and positive CLCA2expression (p =0.038 and p =0.019, respectively).

The combination of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin lead to the adequate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.

Increased industrial activities leads to prolonged human exposure to industrial pollutant such as cadmium (Cd). ‍Chronic exposure to Cd in Mammals and also human being, can cause damages to various organs and particularly kidneys and liver. The goal of this study was to investigate the prophylactic effects of combined selenium (Se) and ascorbic acid supplement in rat cadmium toxicity.

Sixty adult male Wistar rats were divided into 10 groups: one control, one sham, and two clusters of 4 intervention groups which were fed with 1 or 5 mg Cd /kg water, for 28 days. The ascorbic acid supplement was added to the drinking water of four groups (10 mg/l). Four groups received intraperitoneal Se (1 mg/kg) at day 1, 5, 10, 15, 20, and 25. Finally, Cd concentration was measured by atomic absorption spectrophotometry in liver and kidney sections. Furthermore, pathological changes were investigated in these sections.

The results showed weight gain in Cd groups which received ascorbic acid and Se, in contrast to weight loss in parallel groups without vitamin C and Se. The stronger necrosis and inflammation have been observed in group received 5 mg/kg Cd compared to group with 1 mg/kg Cd (p <0.05). In addition, the cadmium level was higher in untreated groups without any supplements, significantly (p <0.05).

The drinking water with ascorbic acid has prophylactic effects across cadmium, and combination of Se and ascorbic acid have more prophylactic effects in both kidney and liver of rat to decrease the Cd toxicity.

Cervical intraepithelial neoplasia (CIN) is a dysmaturation process in squamous cells in epithelial layer, which highly increases the risk of developing cervical cancer. The aim of this study was to compare the expression of three biomarkers, p16, p63, and CK17 in patients with CIN and in those with atypical squamous metaplasia (ASM).

In this study, 100 patients underwent a colposcopy-guided cervix biopsy. Immunostaining for the biomarkers was undertaken on tissue samples containing ASM (n=50) and CIN (n=50).

Immunostaining for CK7, P63, and P16 in patients with CIN significantly increased compared to ASM subjects.

The expression of CK17, P63, and P16 in CIN varied from that in ASM. The mentioned biomarkers were reliable factors to distinguish ASM from CIN; however, all biomarkers could differentiate CIN from its mimics due to their high degree of sensitivity and specificity.

This study was conducted to evaluate the frequency of JAK2, CALR and MPL mutations in with BCR-ABL myeloproliferative neoplasms and their association with demographic data and hematologic parameters in a referral center, in the Middle East.

Seventy-one patients with BCR-ABL negative myeloproliferative neoplasms were evaluated for JAK2 V617F, CALR type 1, type 2, and MPL by allele-specific PCR and conventional PCR from 2018 to 2019.

 Twenty three patients were categorized as polycythemia vera and demonstrated JAK2 V617F in 91.3 % of these cases. Thirty-eight patients were classified as essential thrombocythemia and showed JAK2 V617F in 52.6%, CALR type 1 in 18.4%, CALR type 2 in 7.9% and no mutation in 21.1%. Seven patients were recognized as primary myelofibrosis and exhibited JAK2 V617F mutation in 57.1%, CALR type 1 in 14.3 %, CALR type 2 in 14.3% and no mutation in 14.3%. Three patients were diagnosed as MPN, unclassifiable and revealed JAK2 V617F mutation in 33.3% and no mutation in 66.6%.The age (59.15±13.10) and neutrophil percent (70.78±10.14) were higher in patients with JAK2 mutation compared to other mutations (p=0.000, and p=0.03). Platelet count was significantly higher in patients with CALR type 1 mutation (1240400± 402053) (p=0.000).

JAK2 V617F was was associated with patients’ higher age and higher neutrophil count in CBC. CALR mutation had an association with higher platelet count. No MPL mutation was found in this study and it seems that its frequency is lower than what is expected in this region.

Galectin-8 has relationships with cell growth and metastasis of some cancers. Due to controversy in the clinical significance of this protein in the cancer process, we investigated its roles in the development of head and neck squamous cell carcinoma.

This study was performed on 93 samples of patients with Squamous Cell Carcinoma or dysplasia of the head and neck, who underwent biopsy or surgery from 2015 till 2017 in Boo-Ali SINA hospital of Sari, Iran. The relevant paraffin embedded tissue blocks were obtained from archive of pathology and evaluated for galectin-8 by immunohistochemistry. The association between expression of galactin-8 and age, sex, location and stage of disease were assessed. To compare expression rate between the groups, Mc-Nemar, Chi-square and Fisher's exact tests were used. The P-value  

Strong cytoplasmic and nuclear galactin-8 staining was observed in 97.6% cases of normal tissues while 77% of dysplastic lesions and 69% of the cancers revealed negative immunoreactivity. The intensity of expression in dysplastic and malignant tissues was significantly reduced compared with normal tissues (p =0.0001). The expression of galectin-8 did not correlate with stage (p =0.303), lymph node involvement (p =0.326), tumor grade (p =0.769), distant metastasis (p =0.748), and age (p =0.574).

We observed that the expression of galectin-8 in dysplastic and malignant squamous epithelium significantly reduced compared with the normal counterpart of them in the head and neck. It may contribute to malignant transformation of head and neck squamous cells.

Colorectal Cancer (CRC) is the third most common cancer after prostate (breast in women) and lung cancer; it is also the third cause of cancer deaths reported in both men and women in 2020. Currently, the most commonly used diagnostic tools for CRC are colonoscopy, serological methods, and other imaging techniques. Despite the benefits and abilities of these methods, each of them has disadvantages that reduce its functionality and acceptance. The aim of this study was identifying specific and non-invasive genetic biomarkers to diagnose colorectal cancer.

In this study, changes in the expression of HLTF and SEPT9 genes were evaluated by Real Time PCR in blood and tissue samples of CRC patients. A total of 100 samples (50 Blood and 50 Tissue samples) were evaluated with a definite diagnosis of CRC in Firoozgar Hspital, Tehran, Iran, in 2018. The QPCR method was used to compare the expression of candidate genes between the patients group and control group in both samples. Sensitivity and specificity of the test were examined using ROC curve analysis.

The results showed a significant down-regulation in the expression of both selected genes in tissue and peripheral blood in the various stages of the CRC. The sensitivity and specifity of both genes was about 80%.

The findings showed that the two candidate genes can be suggested as specific biomarkers for diagnosis of CRC using the peripheral blood as a non-invasive method. For a definite conclusion, more research is needed.

Polyomavirus-associated nephropathy (PVAN), mainly caused by the BK virus, is one of the most important infectious complications of kidney transplantation. The leading histopathologic characteristics of PVAN is viral cytopathic effects, such as nucleomegaly with smudged or clumped chromatin and intranuclear ground-glass inclusion, mostly in tubular epithelial cells. Moreover, tubular necrosis, tubulitis, interstitial inflammation, atrophy, and fibrosis have been noted. Positive immunohistochemistry (IHC) staining for SV-40 highlights the infected epithelial cells of renal tubules.

A total of 85 core needle biopsies of transplanted kidneys were evaluated histologically and were stained for SV-40 using the IHC method. In addition, a follow-up of graft failure was performed.

Our findings revealed that the frequency of polyomavirus infection in kidney transplant patients in the Northeast of Iran is 4.7%. There was no significant correlation between PVAN and graft rejection. Although a higher rate of graft loss was observed in PVAN patients, in comparison with non-PVAN patients (25% vs. 14.8%), the difference was not statistically significant. Moreover, patients with immunohistochemically confirmed PVAN and those with histopathologic features of viral-like cytopathic effects had significantly lower graft survival in the follow-up period (42.5 vs. 196.8 months and 109.4 vs. 205.7 months, respectively).

The frequency of polyomavirus infection in kidney transplant patients in the Northeast of Iran is 4.7%. There was no significant correlation between PVAN and graft rejection. Furthermore, we observed that polyomavirus infection accelerates the course of graft loss.

Chondroma is a benign cartilaginous tumor. It is found very rarely in the head and neck.

This report describes a 25-year-old woman who presented with generalized headache from 4 months ago. The patient underwent excisional surgery. The histological examinations revealed benign cartilage forming tumor, compatible with chondroma. The radiologic and histologic correlation confirmed the diagnosis. Based on the diagnosis, the patient received no more treatment.

We concluded that intracranial chondroma should be included in the differential diagnosis of a calcified mass on skull imaging. Proper diagnosis is necessary for further patient management.

Mesonephric adenocarcinoma of the uterine cervix, an extremely rare tumor of the female genital tract, derives from the remnants of embryonic mesonephric ducts and its prognosis, diagnosis and treatment is rather challenging. We report a case of a 46-year-old woman with history of abnormal uterine bleeding and an enlarged uterine cervix on physical examination without obvious mass lesion. She was clinically underdiagnosed with cervical myoma and mesonephric hyperplasia. After simple hysterectomy, stage IB2 mesonephric adenocarcinoma was diagnosed. Despite adjuvant chemoradiation, she presented with peritoneal and locoregional recurrence in less than a year. In the presence of abnormal bleeding and cervical mass, mesonephric hyperplasia in cervical biopsy specimen should be suspected for adenocarcinoma. Radical hysterectomy and complete staging with or without salpingo-oophorectomy is the mainstay of treatment. Despite all ambiguities, due to small number of the reported cases, the overall prognosis seems to be less favorable than conventional cervical adenocarcinoma.

Germ cell teratomas belong to nonseminomatous germ cell tumors and account for 95% of malignant testicular tumors. Regarding the current World Health Organization (WHO) criteria, testicular teratomas are divided into prepubertal and postpubertal subtypes based on patients’ age. The term “burned-out testicular tumor” is a very rare condition referring to a regressed testicular tumor which presents with its metastases without any clinical finding in the testicle. Metastasis can be the presentation of postpubertal teratoma in 22-37% of cases. In scar associated teratoma (burn-out component), the metastasis rate is 66%. We reported a rare case of postpubertal teratoma in a 34-year-old male who presented with multiple liver masses initially. Liver biopsy revealed poorly differentiated adenocarcinoma probably from gastrointestinal (GI) tract. The upper and lower GI endoscopy were normal. Scrotal ultrasonography showed a hypoechoic cystic intratesticular lesion in the left testis. He underwent radical orchiectomy and the histopathology examination revealed postpubertal teratoma with burned out component. He underwent proper treatment and is still under follow up. As a result, in a young male patient who presented with a retroperitoneal mass or poorly differentiated carcinomas of an unknown primary site, using light microscopy and immunohistochemical profiling alone may be inadequate. Therefore, scrotal screening and physical examination of the scrotum and bilateral testis should be considered to exclude possibility of a metastatic progression from a testicular germ cell neoplasia.

Dendritic cells (DCs) are key arms of immune system, which act in antigen presenting processes, and are considered as a bridge between innate and adaptive immune responses. DCs are found in both lymphoid and non-lymphoid organs. They are called interdigitating dendritic cells (IDCs) in secondary lymphoid organs. IDCs lack lineage surface markers and are positive for S-100 and vimentin. IDC sarcoma (IDCS) is a very rare neoplasm, which mainly affects lymph nodes, though there are reports of extra-nodal involvement. IDCS is thought to have poor prognosis. Although there is no consensus on the treatment modalities, such options as radicalsurgery, chemotherapy, and radiotherapy are performed depending on severity and site of the lesion. In this study, we present a case of IDCS in a 53-year-old male with a history of several skin lesions and prior diagnoses of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and metatypical carcinoma (MTC).