Iranian Journal Of Pathology
Volume:18 Issue: 4, Autumn 2023

The most frequent type of cancer found in the endocrine system is thyroid carcinoma. Among well-differentiated thyroid malignancies, the most commonly occurring type is identified as papillary thyroid carcinoma (PTC), which makes up 70-90% of the cases. A subtype of PTC is papillary thyroid microcarcinoma (PTMC), which includes tumors smaller than 10 mm in diameter. Due to the advancements in diagnostic techniques, the incidence of this type of cancer is on the rise. In this study, we aimed to analyze the factors worsening the PTMC prognosis.

In the first step, we searched various databases for the factors affecting this tumor. The relevant articles were collected and different outcomes of this tumor and its associated factors which were studied in more than one article, were classified. Finally, we conducted a meta-analysis of these outcomes and their related factors.

In the meta-analysis, a significantly association was found between the following factors: recurrence with gender (P<0.001) lymph node metastasis (LNM) (P= 0.003), and extrathyroidal invasion (P<0.001); lymph node metastasis with extrathyroidal invasion (P<0.001), and multifocality (P<0.001); central lymph node metastasis (CLNM) with gender (P=0.001), tumor size (P<0.001), extracapsular invasion (P<0.001), lateral cervical lymph node metastasis (P<0.001), and extrathyroidal invasion (P<0.001); lymph node metastasis resulted in poor outcomes (P<0.001); and finally tumor size with BRAFV600E mutation (P<0.001).

In conclusion, it is essential to note that greater awareness and understanding of this tumor characteristics and special and separate attention to PTMC can significantly improve the society overall health.

Interleukin-6 (IL-6) is involved in inflammation and has a significant role in chronic lymphocytic leukemia (CLL) progression. Accordingly, IL-6 level may increase in CLL-affected patients compared to healthy individuals. The -174G>C single nucleotide polymorphism (SNP) in IL-6 promoter region has been related to differences in IL-6 transcription. Therefore, we investigated the possible association of IL-6 polymorphism with CLL.

We examined the -174G>C SNP in IL-6 gene and studied its possible relationship with CLL in affected patients and in healthy controls using Amplification Refractory Mutation System- polymerase chain reaction genotyping method.  IL-6 plasma level was measured in both studied groups.

According to the results, IL-6 mean plasma concentration was increased significantly in the CLL patients compared to the controls. However, 174G>C genotype of the IL-6 gene was not associated with CLL. Furthermore, there were no significant differences in the distribution of allele and genotype frequencies between the CLL-affected patients and the controls (P>0.05).

Our study showed that -174G>C SNP in promotor of IL-6 gene could not be considered a risk factor for CLL. Larger prospective studies should be performed to confirm our results.

Unnecessary pre-operative ordering of red blood cells (RBCs) in elective surgeries increases costs and waste of blood inventory. Maximum surgical blood order schedule (MSBOS) is a helpful strategy in the estimation of blood units needed for surgery and the prevention of overconsumption. In this study, an MSBOS for pediatric cardiac surgeries is designed.

In this cross-sectional study, we included all pediatric patients who underwent elective cardiac surgery in Children’s Medical Center in Tehran, Iran, from March 21, 2019, to September 22, 2019. Data consisted of the type of surgery and the number of blood units transfused and units cross-matched, based on which cross-match to transfusion ratio (CTR), the transfusion index (TI), and transfusion probability (T%) were calculated.

Overall 205 pediatric patients were included in the study. Four hundred and ten RBCs units were cross-matched, and 262 were transfused. The overall results of the CTR, T%, and TI for all the eight types of cardiac surgery were 1.56 (410/262), 76% (157/205), and 1.28 (262/205), respectively. The raw MSBOS for cardiac surgeries included ventricular septal defect, tetralogy of fallot, dextro-transposition of the great arteries, atrial septal defect, aortic coarctation, patent ductus arteriosus, pulmonary stenosis, and pacemaker insertion, which were 1.58, 1.03, 1.54, 1.66, 0.77, 0, 1.25, and 0 unit, respectively, and the figures were rounded up.

Accurate MSBOS protocols reduce cross-match workload in laboratories, lead to the appropriate use of blood stocks with less wastage, save human and economic resources, and eventually, promote patient safety.

Human epidermal growth receptor-2 (HER2) gene amplification is an important predictive and prognostic factor in breast cancer treatment. However, the expression of HER2 determined by immunohistochemistry (IHC) is considered as borderline in some cases, and confirmation of the HER2 status by either fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) is necessary for correct treatment decision-making. Considering the high cost of FISH and CISH, we aimed to investigate whether clinicopathological findings of the tumor could predict the HER2 status.  

A retrospective study was performed using the data from 584 patients with breast cancer with HER2-borderline disease, confirmed by IHC. Final HER2 status, pathologic tumor size and type, nodal involvement, Ki67 index, presence of estrogen and progesterone receptors (ER, PR), lymphovascular invasion (LVI), and stage were retrieved from the clinical records.

One hundred twenty-one (20.7%) patients were HER2-positive according to the FISH or CISH results. Logistic regression analysis showed that the pathologic size was positively associated with HER2 positivity with an odds ratio (OR) of 1.02 (95% CI: 1.01-1.04). In addition, the adjusted OR illustrated a statistically significant association between HER2 positivity and PR negativity (OR= 2.22, 95% CI: 1.29-3.83).

In HER2 borderline breast cancer, HER2 positivity significantly increases with tumor size and PR negativity. Further studies are recommended that may find an applicable model to predict the actual status of HER2 in borderline cases.

Formalin-fixed paraffin-embedded archived tissues are useful for the genetic analyses and assessment of some patients’ disease history, including infectious diseases. However, there is no established protocol for extracting bacterial DNA from the archived specimens. In this study DNA was extracted from the archived H. pylori-positive gastric biopsies by some modifications applied to the previously published protocols. The quality of the extracted DNA was assessed by amplifying H. pylori-specific 16S rRNA gene.

Fifty H. pylori-positive gastric biopsies obtained, fixed, and embedded in paraffin blocks during 2002-2008 were recruited. After paraffin removal, simultaneous proteinase K treatment and mechanical disruption using glass beads were used for the digestion of gastric tissues. DNA extraction was performed by adding one step of phenol treatment and two steps of incubation to the conventional phenol-chloroform method. The quantity and quality of the extracted DNA samples were assessed. Also, PCR was performed using primers specific for the H. pylori-specific 16S rRNA.

The electrophoresis showed that intact DNAs were recovered from all biopsy samples. Amplification of the PCR products with the size of 519bp confirmed the presence of H. pylori-specific 16S rRNA gene in all the biopsies.

A 100% success rate for the amplification of H. pylori-specific 16S rRNA gene was achieved from all the samples. In this regard, the designed modified method resulted in the effective removal of interfering contaminations and enhanced the quality of the extracted bacterial DNA from the archived tissues. These modifications may contribute to better extraction of the intact DNA from different bacteria present in human tissues.

Staphylococcus aureus causes various hospital- and community-acquired infections. This study aimed to investigate the phenotypic and genotypic characteristics of erythromycin and inducible clindamycin resistance, virulence gene profiles, and spa types of S. aureus isolates collected from patients in Ardabil Province, Iran.

A total of 118 clinical S. aureus isolates, including 50 (42.4%) methicillin-resistant S. aureus (MRSA) and 68 (57.6%) methicillin-susceptible S. aureus (MSSA) strains, were investigated. Resistance patterns were determined by the disk diffusion method and minimum inhibitory concentration (MIC) test. Inducible macrolide-lincosamide-streptogramin B (iMLSB) resistance was detected using D-test method. The polymerase chain reaction (PCR) was used to identify the virulence and resistance-encoding genes. Additionally, the spa types of the isolates were determined using the PCR, followed by sequencing.

In total, 49.1% (58/118) and 44% (52/118) of the isolates were resistant to erythromycin and clindamycin, respectively. Overall, 13.5% (16/118) of the isolates showed the iMLSB resistance phenotype. The ermC gene (72.4% [42]) was the most frequent erythromycin resistance-encoding gene, followed by ermA (60.3% [35]), ermB (60.3% [35]), ermTR (51.7% [30]), and msrA (15.5% [9]) genes among erythromycin-resistant isolates. The virulence genes hla, hld, sea, LukS PV, tst, seb, sed, eta, sec, and etb were detected in 93.2%, 74.5%, 70.3%, 32.2%, 29.6%, 17%, 8.5%, 8.5%, 5.9%, and 4.2% of the isolates, respectively. Ten different spa types were identified for 58 erythromycin-resistant S. aureus strains, of which t030 and t078 types were the most common types.

A high frequency of macrolide- and lincosamide-resistant S. aureus isolates with different genetic backgrounds of resistance and virulence may be  found  in patients in Ardabil Province, Iran.

Formaldehyde is an irritating substance that is categorized as a definite carcinogen (Group A1), according to the International Agency for Research on Cancer (IARC). This study was conducted to determine the role of this substance in the frequency of micronuclei (MN) in the buccal mucosal cells due to long-term exposure of the pathology staff to formaldehyde.

In this case-control study, 32 pathology laboratory staff members were assigned to the case group, and 32 staff members who were not exposed to formaldehyde were assigned to the control group. Buccal mucosa cells were collected with a wet spatula and stained with Papanicolaou stain. In each sample, 500 cells were counted; then, the frequency of MN and the average number of MN in the micronucleated cells were assessed and compared between the 2 groups using the independent t test. Furthermore, the relationship between gender and MN was evaluated using the independent t test. The relationship between years of exposure and time of exposure during the day (in hours) for the case group, as well as the relationship between age and frequency of MN was analyzed using the Pearson correlation coefficient.

The mean frequency of MN in exfoliated buccal cells was 18.33±12.36 in the case group, which was significantly higher than the control group (10.55±6.22; P=0.003). The difference in the mean number of total MN in the micronucleated cells was not significant between the case and control groups (P=0.11). The relationship between sex, age, and years of exposure with the mean frequency of MN and the total number of MN in the micronucleated cells was not significant. The relationship between exposure time during the day and both the mean frequency of MN and the total number of MN in the micronucleated cells was significant (P=0.03).  

Formaldehyde exposure and extended time of exposure during the day can increase the frequency of MN, which can prognosticate the incidence of precancerous and cancerous lesions. Therefore, continuous exposure to formaldehyde can be considered an occupational health hazard, though further studies are needed to confirm this result.

Antibiotic resistance, especially in the form of multidrug-resistant (MDR), is a big problem, especially in intensive care units (ICUs). This study aimed to evaluate antibiotic resistance and MDR patterns among patients hospitalized in the ICUs in one of the large referral centers in Iran.

The present study was conducted at Imam Khomeini Hospital in Tehran (a great referral hospital), which admits critically ill patients requiring ICU services. To determine the rate of positive cultures for resistant strains, the patient’s blood specimens were sent to the laboratory of the hospital for inoculation on proper culture media within 2 hours of extraction. Antimicrobial susceptibility tests were done using the Bauer–Kirby disk diffusion method.

A total of 1,755 samples were collected from the patients to assess microbial strains and antibiotic resistance. The most common microbial strains detected in the cultures extracted from peripheral blood samples were Klebsiella pneumonia (22.1%), Staphylococcus epidermidis (7.9%) and another coagulase-negative Staphylococcus (15.0%). The antibiogram test showed antibiotic resistance in 1,509 cases, leading to a resistance prevalence rate of 85.9%. The most common antimicrobial resistance observed was against cotrimoxazole (61.7%), ciprofloxacin (51.3%), imipenem (50.0%), and ampicillin (49.6%). The rate of MDR was found to be 96.3%.

In Iran’s ICUs, a significantly high level of antibiotic resistance may be seen especially the MDR pattern, which indicates the need to change the pattern of prescribing and managing these drugs in ICU centers.

The Milan system of classification of the salivary gland lesions came up with an aim to establish a universal reporting protocol. The aim of this study was to classify the fine-needle aspiration cytology (FNAC) cases of salivary gland according to the Milan system.

All the cases presenting with salivary gland lesion for FNAC were considered. The clinical data was recorded. Cytology findings were analyzed according to the Milan System. Histopathological correlation was made wherever available.

A total of 100 cases of salivary gland lesions were collected and categorized according to the Milan system. They were correlated with histopathology in 45 cases. The patients’ age varied from 2-85 years. Parotid gland was the most commonly affected. Category 1 (non-diagnostic) comprised of three cases. Category 2 (non-neoplastic) had 40 cases. In category 4a (benign) there were 43 cases, and the most common lesion was pleomorphic adenoma. Category 5 (suspicious of malignancy) comprised of 3 cases. Category 6 (malignant) comprised of 11 cases and the most common lesion was mucoepidermoid carcinoma. In category 2, the cytological findings of 5 cases were concordant with histopathology while, 2 were discordant. In category 4a (benign), 20 cases were concordant, and 3 cases were discordant (2 cases were mucoepidermoid carcinoma, 1 was adenoid cystic carcinoma on histology). The risks of malignancy in NN, AUS, benign, SOM, and malignant were 33.3, 2.5, 0, 7, 66.6, and 100%, respectively.

Milan system of reporting salivary gland cytopathology may have great potential of escalating clinical communication and may guide appropriate treatment.

Acinetobacter baumannii strains harboring Meallobetalactamases (MBL) pose a significant threat in the context of nosocomial infections. The present investigation was undertaken with the objective of devising a Multiplex PCR methodology for the concurrent detection of MBL genes within A. baumannii strains prevalent in Tehran City, Iran.

Between October 2020 and February 2021, 100 strains of A. baumannii were procured from burn specimens of hospitalized patients at Motahhari Hospital in Tehran. The identification of A. baumannii strains involved conventional biochemical techniques, coupled with confirmation of the presence of the bla OXA-51 gene. Antibiotic susceptibility was assessed using the Kirby–Bauer disc diffusion test. MBL-producing strains were characterized through a phenotypic approach employing the combined disk test, alongside Multiplex PCR for the simultaneous identification of bla VIM, bla IMP, bla GIM, and bla NDM genes. Statistical analyses were conducted using the chi-square test, with SPSS version 20.0 employed for data processing.

Among 100 strains examined, 96.1% exhibited positivity for MBL, as determined by the combined disk test. The study revealed a predominance of extensively drug-resistant (XDR) strains, with colistin demonstrating the highest level of sensitivity. The genotypic assay unveiled that Multiplex PCR identified bla VIM, bla NDM, and bla IMP in 20 strains, bla VIM and bla NDM in 30 strains, and exclusively the bla NDM gene in 45 strains. Notably, the Multiplex PCR technique exhibited the capacity to concurrently detect MBL genes (bla VIM, bla IMP, bla GIM, bla NDM) in 2 strains.

The current investigation underscores prevalence of the bla NDM gene within clinical strains of A. baumannii. Furthermore, Multiplex PCR emerges as a robust and highly sensitive technique for rapid discernment of the MBL genes within in A. baumannii strains.

Acute Promyelocytic Leukemia (APL) is a medical emergency with potentially fatal complications. APL primarily results from a chromosomal translocation (t(15;17)(q22;q21)), leading to the formation of the PML-RARA fusion gene with three possible isoforms. This study aims to investigate the characteristics of Iranian APL patients, the distribution of PML-RARA isoforms, and survival analysis.

We included 145 consecutive eligible patients in this study. Data were collected through archived documents and phone inquiries, following consent. Subsequently, we analyzed the data using SPSS software version 26.0.

We examined 75 men and 70 women, with a mean age of 34 years (range: 2-78 years). Besides t(15;17) (q22;q21), 45.6% had other chromosomal abnormalities. The prevalence of bcr1 and bcr3 isoforms was 73% and 27%, respectively. bcr3 correlated with higher white blood cell (WBC) counts, additional chromosomal abnormalities, and faster Complete Hematologic Response (CHR). Early death occurred in approximately 36% of all patients. The mean overall survival time was 73.5 months, with 120-month survival rates of 53.8% for all patients and 83.9% for those who achieved CHR. Univariate analysis identified old age, relapse, lower platelet (PLT) counts, higher WBC counts, and leukocytosis as survival risk factors. However, in multivariate analysis, only old age and higher WBC counts were identified as adverse prognostic factors.

In Iranian APL patients, bcr1 predominates, while bcr3 correlates with higher WBC counts, high-risk categorization, additional chromosomal abnormalities, and faster CHR. Survival is negatively impacted by old age, relapse, lower PLT counts, higher WBC counts, and leukocytosis.

Tumors of the ovarian epithelial type of testis are an infrequent entity. We report a case of borderline serous tumor in an 18-year-old male who presented with a right testicular mass, clinically suspicious of carcinoma. After right inguinal exploration, two pedunculated para-testicular masses were identified in the appendix of the right testis and epididymis. The histological features were as complex papillary structures lined by columnar cells with mild to moderate pleomorphism. Microscopically, features of borderline serous testicular tumors are identical to the morphology of the same tumors encountered in the ovarian counterparts. These tumors usually reveal papillae with fibrovascular cores lined by stratified cuboidal to columnar epithelium. This case highlights a need for clinicians and pathologists to be aware of this infrequent entity and improve the best patient management attitude. Serous epithelial tumors are common ovary tumors but are very rare entities in the testis. These tumors originate from the remnant of Mullerian ducts or Mullerian metaplasia of tunica vaginalis and are nonaggressive, even associated with extra ovarian spread, and have outstanding prognosis. A review of the literature has shown nearly fifty reported cases worldwide, and most of the cases occur in young to middle-aged adults.

The capability of the urinary tract to undergo metaplastic changes such as squamous, intestinal, glandular, mucinous, or ciliated epithelium in renal pelvis has been previously reported, which hypothetically is due to the mechanical irritation of the transitional epithelium. However, transitional metaplasia is a rare presentation in the collecting ducts. The aim of this paper was to report this type of extremely rare metaplasia and to inform pathologists that they may encounter this kind of metaplasia. A 25-year-old man, a known case of vesicoureteral reflux (VUR), referred to the Imam Reza Hospital; affiliated to the Mashhad University of Medical Sciences, for bilateral nephrectomy. Gross evaluation of bilateral nephrectomy specimens showed atrophic kidneys and dilated pelvicalyceal systems. The light microscopic evaluation showed transitional metaplasia in the background of chronic pyelonephritis, confirmed by GATA3 nuclear immunohistochemical stain.  In this study, we presented a rare case of a renal collecting duct with transitional epithelial lining replacing the normal epithelium as a metaplastic change, with the hypothesis that previous medical history including VUR, or hemodialysis could be the trigger for the metaplastic change, which should be confirmed by further studies.

Syringocystadenoma papilliferum is a rare benign adnexal tumor that originates from the apocrine and eccrine glands. It mainly manifests as a solitary lesion in the head and neck; however, rarely, it may involve the trunk and limbs, typically with a linear pattern. Here, we report an extremely rare case of congenital linear syringocystadenoma papilliferum on the left buttock near the anus in a 6-year-old girl. This lesion should be considered in the list of differential diagnosis of linear lesions in order to prevent complications with proper diagnosis, treatment or follow-up.

Conjunctival melanoma is an uncommon tumor that is likely to recur and carries an overall mortality rate of approximately 30%. Melanoma   arises from melanocytes, most often in sun-exposed skin. Less commonly, melanoma originates from other tissues such as the uvea, rectum, mouth, respiratory tract, and conjunctiva. Conjunctival melanoma represents only 1.6% of all noncutaneous melanoma. Herein, we reported a case of conjunctival melanoma followed by reviewing the literature to provide an optimal diagnostic approach.