Iranian Journal of Pathology

Abstract Extracellular vesicles (EVs) are cell-derived vesicles that play a critical role in host-pathogen interactions, facilitating intercellular communication and transporting both pathogen- and host-derived molecules during infection spread. To regulate their environment, for instance, by modulating innate and adaptive inflammatory immune responses, pathogens may alter the composition of EVs produced by infected cells. Gastric cancer is one of the leading causes of cancer-related deaths worldwide, and Helicobacter pylori infection is considered a significant risk factor for its development. This cancer is characterized by significant inflammation mediated by EVs generated from infected host cells. H. pylori contributes substantially to inflammation, promoting disease progression. Moreover, H. pylori produces and releases vesicles known as outer membrane vesicles (H. pylori-OMVs), which contribute to the shrinkage and cellular transformation of the gastric epithelium. Although the vacuolating cytotoxin A (VacA) plays a critical role in pathogenesis, its association with EVs in H. pylori has not been previously addressed. Understanding the roles of extracellular vesicles and VacA during H. pylori infection—whether they benefit the host or the pathogen—could pave the way for new treatment approaches. This review briefly discusses the role of VacA and extracellular vesicles in the growth and pathogenesis of H. pylori.

Abstract Background & Objective: There is controversy whether eosinophils are involved  in the pathogenesis of psoriasis. This study aims to assess the quantity of eosinophils in pathological specimens obtained from individuals diagnosed with psoriasis. Methods: cross-sectional and retrospective study 91 skin samples were obtained from patients with diagnosis of psoriasis. Two experienced dermatologists thoroughly reviewed the specimens' demographic characteristics, clinical features, and pathological attributes. Subsequently, eosinophils were counted within all microscopic fields, utilizing a magnification of 200. Results:  Eosinophils were present in approximately 70.3% of the examined samples, with a mean eosinophil count of 2.42±0.63. Although no significant correlation was observed between the clinical subtype and the average eosinophil count, eosinophils were most commonly detected in the cases presenting generalized pustular psoriasis (100%) and vulgaris types (71.11%). Notably, patients exhibiting Munro's microabscess and dilated papillary dermal blood vessels exhibited a significantly higher number of eosinophils (P=0.007 and P=0.039, respectively). Additionally, a notable association was identified between presence of spongiosis, and eosinophil counts in the pathological samples (P=0.04). Conclusion: Presence of eosinophils may not contradict a diagnosis of psoriasis. Furthermore, a notable association may be observed between the number of eosinophils and  presence of spongiosis, dilated dermal papillary vessels, and Munro's microabscess.

Abstract Background & Objective: Cervical cancer is the second most common malignancy among women worldwide. The Receptor for Activated C Kinase 1 (RACK1) has a key role in regulating the pathways of cell signaling, angiogenesis, cell migration, invasion, and metastasis. This study investigated the association of polymorphisms rs1279736 and rs3756585 with cervical cancer.
Methods:  In this study, 100 LB pap-smear and paraffin block samples of cervical squamous carcinoma associated with Human papillomavirus (HPV) were selected along with 100 LB smear cytology samples from healthy women with normal pap smears, serving as the control group. Genomic DNA was extracted from the samples, and the polymorphisms rs1279736 and rs3756585 in the RACK1 genes were examined using the RFLP-PCR and ARMS-PCR methods, respectively.
Results: The rs1279736 polymorphism shows that the chance of cervical cancer in individuals with CA and AA genotypes is 3.772 and 1.852 times that of CC genotypes, respectively. This suggests that the A allele is involved in developing cervical cancer (P=0.005; OR=2.113). The rs3756585 polymorphism indicates that the chance of cervical cancer in TG and GG genotypes is 0.373 and 4.235 times that of TT genotypes, respectively. This also points towards the involvement of the G allele in the development of cervical cancer (P=0.032; OR=1.800). Also, there was no significant relationship between the genotype of polymorphisms, age, and subtype of papillomavirus 16 and 18 in patients.
Conclusion: The present study was conducted for the first time. Our results showed that two polymorphisms are significantly associated with cervical cancer.

Abstract Background & Objective: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Fite-Faraco (FF) is the routine staining method used to demonstrate the presence of Mycobacterium leprae in tissue sections. Fluorescent microscopy (FM) can help visualize lepra bacilli better. The present study compares two methodologies, fluorescent microscopy, and Fite-Faraco, in detecting Mycobacterium leprae in tissue sections.
Methods: Histopathology of skin biopsies in 60 cases of Hansen's were evaluated with FF stain. The performance of Auramine- Rhodamine Fluroscencent stain was compared with conventional FF staining in identifying Lepra bacilli.
Results: A total of 60 clinically and histopathologically confirmed cases of Hansen’s disease were included in this ambispective study. The cases were sub-classified into various histological categories. Auramine-rhodamine fluorescent staining was performed and examined under a fluorescent microscope with an LED light illuminator. The bacteriological index (BI) was calculated under an oil immersion field for both Fite-Faraco (FF) staining and fluorescent microscopy (FM), graded from zero to six plus according to Ridley’s logarithmic scale. Lepra bacilli were identified in 70% of patients on FF staining, while fluorescent microscopy showed positivity in 80%. The mean BI calculated by FM (2.48) was significantly higher than that by the FF method (2.18), and more multibacillary disease was identified by fluorescent staining compared to FF staining.
Conclusion: It is advantageous to use fluorescent microscopy as an adjunct to conventional Fite-Faraco stain especially in cases where the latter fails to detect lepra bacilli and in a clinically suspected multibacillary disease.

Abstract Background & Objective: Hashimoto's thyroiditis (HT) is one of the most common thyroid disorders and is characterized by manifestations attributed to thyroid gland damage and inflammatory conditions. Disturbances in thyroid hormones have physiological effects on lipoprotein metabolism and liver enzymes. CTRP family: C1q/TNF-related protein (CTRP) is an adipokine superfamily of proteins. Its essential role is anti-inflammatory activation, insulin sensitization, and regulation of blood lipids. In this study, we investigated the levels of CTRP-4 and CTRP-12 in the serum of HT patients and determined their association with biochemical factors.
Methods: The study included 60 participants, divided into HT patients and control groups. Diagnostic criteria for HT patients included anti-thyroid peroxidase antibodies (anti-TPO)>50 IU/mL. Serum levels of CTRP-4, CTRP-12, and anti-TPO were measured using an Enzyme-Linked Immunosorbent Assay.
Results: Our findings showed that the CTRP-4 and CTRP-12 levels in HT patients were higher than in the control groups (P=0.012 and P=0.003, respectively). HT patients also exhibited higher fasting blood glucose (FBG), cholesterol, TG, HDL, and LDL serum levels. Spearman's correlation analysis revealed a positive association between serum levels of CTRP-4 and CTRP-12 and anti-TPO (respectively, r= 0.295, P=0.022 and r = 0.346, P=0.007).
Conclusion: Our findings showed that the CTRP-4 and CTRP-12 levels in HT patients were higher than those in the control groups. These factors probably play a role in the pathogenesis of Hashimoto's thyroiditis. The clinical significance of these factors should be evaluated in future studies.

Abstract Background & Objective: Conjunctival lesions have a wide range of histological manifestations that are difficult to distinguish clinically. The gold standard for diagnosis of these lesions is the pathological examination, a costly and invasive procedure that may also adversely affect patients. Therefore, clinical researchers seek less invasive, inexpensive, and easier methods to detect conjunctival lesions. This study aims to compare the accuracy of impression cytology with pathology in patients referred to Farshchian Hospital in Iran. Methods: In this descriptive/cross-sectional study, 64 patients with conjunctival lesions were selected from patients referred to Farshchian Hospital in Hamedan in 2021. A cytology specimen was obtained from the patients and sent to the laboratory. The diagnostic accuracy of this method was compared with pathological results (gold standard). Data were analyzed by SPSS 16 software. Results: The mean age of patients was 54.47 ±16.94 years; 70.3% were male, and 29.7% were female. In the cytologic and pathologic examination, 28.1% of the specimens showed dysplasia, and 71.9% were non-dysplastic. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the cytologic impression compared to the pathologic methods were 91.30%, 77.78%, 91.30%, 77.78%, and 87.5%, respectively. A positive and significant correlation was observed between pathological and cytological diagnosis scores (r=0.825, P-value<0.001). Conclusion: In conjunctival lesions, impression cytology may be  a relatively accurate and sensitive procedure that can distinguish  dysplastic from  non-dysplastic conjunctival lesions.

Abstract Background & Objective: Even though fast advances in the detection and management of bladder carcinoma, the number of deaths remains high. Therefore, the identification of an effective biomarker predicting tumor progression in cancer bladder patients is a crucial issue. This study aims to identify TIPE2 and CD36 expressions in cancer bladder and examine their relationship with clinicopathological data and prognosis.
Methods: Using immunohistochemistry, we investigated 60 specimens of bladder urothelial cancer (UC) for the expression of TIPE2 and CD36 and compared them with clinicopathologic parameters and survival data. Furthermore, we investigate the association between TIPE2 and CD36 expression and Vimentin expression to elucidate the influence of TIPE2 and CD36 on the epithelial-mesenchymal transition (EMT) in UC.
Results: TIPE2 expression was associated with lower stages and prolonged disease-free survival (DFS) and overall survival (OS). Therefore, TIPE2 may be considered a good indicator of UC prognosis. CD36 immuno-positivity was associated with high tumor grade, stages, shorter OS, and DFS. Therefore, the immune positivity of CD36 may be a poor prognostic marker for UC patients. Furthermore, Vimentin expression was directly correlated with CD36 expression and inversely correlated with TIPE2 expression.
Conclusion: TIPE2 and CD36 may be novel biomarkers for predicting tumor metastasis and prognosis in patients with bladder UC and hold promise as therapeutic targets.

Abstract Background & Objective: Even with improvements of colorectal cancer (CRC) treatment strategies, this cancer still has an unfavorable outcome. The primary cause of CRC development and recurrence is chemoresistance. CD10 and Notch1 are among cancer stem cell regulators, and they have roles in cancer progression and chemoresistance. This research aims to evaluate the expression of Notch1 and CD10 in CRC and their relationship with different clinicopathological parameters using immunohistochemistry. Methods: This retrospective study included 100 cases of colorectal carcinoma that were immunohistochemically stained using Notch1 and CD10 antibodies. Expression of Notch1 and CD10 was evaluated and compared with different clinicopathological parameters. Results: Notch1 expression was detected in the tumor and stromal cells in 92% of the cases, while CD10 expression was seen in 31% of tumor cells 79% of stromal cells of the included cases. Their expressions in tumor cells were significantly associated with higher grade (P=0.029 and 0.001), deeper invasion (P=0.01 and 0.002), advanced stage (P=0.012 and 0.001), and distant metastasis (P=0.001 and 0.02). Notch1 expression was positively correlated with CD10 expression (P=0.018). Both Notch1 expression and high CD10 expression in the stromal cells were associated with short overall survival (P=0.003 and 0.01). Conclusion: CD10 and Notch1 may have roles in colorectal carcinoma progression via induction of tumor invasion, metastasis and impairment of tumor response to therapy. CD10 and Notch1 could be used as biomarkers for aggressive CRC and may be considered for future target therapy.

Abstract Background & Objective: Use of fine needle aspiration cytology (FNAC) in the diagnosis of salivary gland neoplasms is controversial due to the diverse morphologic patterns and overlapping features between benign and malignant lesions. The Milan system has been introduced to report salivary gland cytopathology. The present study aimed to reclassify salivary gland lesions according to the Milan system for reporting salivary gland cytopathology (MSRSGC) to determine the risk of malignancy (ROM) and estimate the diagnostic accuracy of the Milan system.
Methods: In this retrospective cohort study, 136 salivary gland fine needle aspiration cytology samples taken from patients referred to Imam Khomeini and Amir-Aalam Hospital, Tehran, Iran, from 2016 to 2021, were retrieved along with the histopathological follow-up.  Cytology smears were reviewed and reclassified based on MSRSGC. In addition, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. 
Results: ROM for each category was 26.7% for non-diagnostic, 12.5% for non-neoplastic, 40% for atypia of undetermined significance (AUS), 0 for benign neoplasm, 0 for salivary gland neoplasm with uncertain malignant potential (SUMP), 100% for suspicious for malignancy, and 100% for malignant group. Sensitivity, specificity, PPV, and NPV in differentiating benign from malignant neoplasms based on MSRSGC were 75.9%, 100%, 100%, and 93.8%, respectively. Diagnostic accuracy was calculated as 94.8%.
Conclusion: MSRSGC may be associated with  a high accuracy in differentiation of  benign and malignant salivary gland neoplasms, indicating its potential value as an effective classification system for reporting salivary gland cytology. The ROM for cytological categories except SUMP can be almost similar to that suggested by MSRSGC.

Abstract Background & Objective: Rhizopus arrhizus, a major contributor to COVID-19-associated mucormycosis (CAM) globally. Nanoliposomal amphotericin B (NLAmB) presents a promising approach due to its enhanced drug delivery and reduced side effects. This study aimed to assess the in vitro antifungal susceptibility of NLAmB against R. arrhizus isolated from CAM patients.
Methods: Thirty-nine R. arrhizus isolated from CAM patients were identified through phenotypic characterization, MALDI-TOF, and the internal transcribed spacer rDNA region (ITS) sequencing approaches. Antifungal susceptibility testing (AFST) for NLAmB, amphotericin B (AmB), posaconazole (PSC), and isavuconazole (ISC) was conducted through broth microdilution methods according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standard E.DEF 9.4. Results were analyzed for MIC ranges, MIC50, MIC90, and distributions.
Results: NLAmB demonstrated superior in vitro efficacy against R. arrhizus (MIC50/90, 0.063/0.25 μg/ml) compared to AmB, PSC, and ISC. PSC exhibited notable activity (MIC range: ≤0.031 - ≥16 μg/ml).
Conclusion: The study emphasized NLAmB's sustained activity, making it a potential alternative to LAmB. Further exploration and clinical correlation are warranted to validate NLAmB in CAM treatment.

Abstract Background & Objective: Phyllodes tumor (PT) is a rare fibroepithelial tumor of the breast exhibiting varied clinicopathologic behavior, ranging from benign to borderline to frankly malignant,based on the presence of infiltrative margins, stromal overgrowth, stromal atypia, cellularity, and mitotic activity. A detailed cytomorphological study of cases of PT was performed, with clinical and histological correlation.
Methods: A cytomorphological study of 17 cases of histologically proven PT diagnosed between Jan 2014 and July 2021 was done retrospectively. Relevant data were obtained, including age at the time of diagnosis, the duration of illness, presenting symptoms, personal and family history, tumor size, tumor localization, and surgical procedure. A detailed cytomorphological assessment of stromal and epithelial components was performed, and further histological correlation was obtained for each case.
Results: The age of the patients ranged from 25 to 65 years old. The chief complaint was a palpable breast mass in all patients. The mean size of the lump was 11.86 cm. A complete cytohistological concordance was achieved among malignant cases. Stromal metaplasia was observed in only one case of benign phyllodes tumor, which was chondroid differentiation, and malignant heterologous component as fibrosarcomatous differentiation in one of the malignant PTs. Each of the benign and malignant phyllode tumors ductal carcinoma in situ (DCIS) of its epithelial component was seen in one case.
Conclusion: Phyllodes must be considered in differential diagnosing a rapidly growing breast lump. Breast imaging has little role in diagnosing phyllode tumors. FNAC or trucut biopsy is mandatory in preoperative diagnosis. An extended follow-up is needed in all cases.

Abstract Background & Objective: Limited literature describes the accuracy of endoscopic ultrasonography–fine needle aspiration (EUS-FNA) cytology in various types of pancreatic epithelial tumors, and this underscores the usefulness of cell blocks, and highlights potential diagnostic pitfalls.  
Methods: This study included 108 patients who underwent EUS-FNA pancreatobiliary cytology followed by surgery. Age, gender, tumor location, tumor size, presence or absence of a cell block, cytologic and pathologic diagnoses, and histologic tumor grade were recorded. Cytologic and pathologic slides were examined, and the cytologic accuracy was determined by comparing cytologic with the histopathologic results as the gold standard. Additionally, the impact of cell block on the cytologic accuracy was assessed.
Results: EUS-FNA cytology showed an overall accuracy of 80%, a sensitivity of 90%, and a false-positive rate below 1%. Pancreatic ductal adenocarcinomas (PDAs) accounted for 65% of cases, followed by neuroendocrine tumors (NETs), solid pseudopapillary neoplasms (SPNs), mucinous cystic neoplasms (MCNs), and chronic pancreatitis. Diagnostic accuracy was higher for PDA and SPN than for NET and MCN and significantly improved to 100% in cases with a cell block.
Conclusion: Combining pancreatobiliary cytology with a cell block significantly enhances diagnostic accuracy, reaching 100%. Moreover, poorly differentiated PDAs and well-differentiated organoid-type tumors, such as NETs and SPNs, demonstrate higher diagnostic accuracy. 

Abstract Background & Objective: Human papillomavirus (HPV) is a major cause of cervical cancer and mortality, particularly in low-income countries. Late diagnosis of cervical cancer often leads to advanced-stage disease, resulting in poorer prognosis and higher mortality, which underscores the critical need for effective early screening methods. Pap smears, colposcopy, and HPV testing are essential for early detection. This study addresses a gap in the literature by comparing the effectiveness of different diagnostic methods specifically in women with multiple high-risk HPV (hrHPV) infections—a population for which limited comparative data exist.
Methods: This prospective cross-sectional study, approved by the Ethical Committee of Qazvin University (IR.QUMS.REC.1400.143), was conducted at Kowsar Hospital from 2022 to 2023 and included 608 patients infected with multiple hrHPV subtypes. Inclusion criteria required hrHPV confirmation by PCR genotyping and excluded patients without colposcopy and biopsy or with a history of cervical dysplasia. Participants underwent Pap smear cytology, colposcopy, and biopsy, with the biopsy specimens examined by a gynecologic pathologist. Statistical analyses included chi-square tests for qualitative variables and t-tests or ANOVA for quantitative variables, with a significance level set at P<0.05.
Results: The average age of the patients was 38.54 years, with the majority aged 30–39 years (43.6%). Common symptoms included vaginal discharge (36.5%) and postcoital bleeding (34.9%). Pap smear results showed ASCUS in 43.6% of cases and LSIL in 39.1%. Colposcopy revealed acetowhite lesions in 45.6% and abnormal vascular patterns in 25.5%. Histopathology indicated that 72.4% of patients had CIN I. Smoking was significantly correlated with colposcopic findings (P=0.044). Colposcopy demonstrated the highest sensitivity (69.1%) for detecting cervical lesions, while cytology had the highest specificity (63.1%).
Conclusion: Pap smear findings provide adequate diagnostic accuracy for hrHPV patients, but colposcopy offers superior sensitivity for detecting cervical lesions. Combining both methods is recommended to improve diagnosis.

Abstract Background & Objective: The resistance genes encoding aminoglycoside-modifying enzymes (AMEs) are now widely prevalent in different populations of Staphylococcus aureus. The study aimed to determine the frequency of AMEs-encoding genes in clinical isolates of S. aureus.
Methods: A total of 105 S. aureus isolates were obtained from the different clinical samples; and then were identified by conventional biochemical tests. The antibiotic resistance patterns of the isolates were characterized by the agar disk diffusion method. The distribution of the AMEs and femA genes was determined by conventional and multiplex PCR.
Results: The aminoglycoside resistance rates of kanamycin, tobramycin, gentamicin, amikacin, and netilmicin were 47.6%, 46.6%, 45.7%, 45.7%, and 26.6%, respectively. 16.1% and 1.9% of isolates were MDR and XDR phenotypes, respectively. 21.9% of S. aureus isolates harbored the femA gene and were determined as methicillin-resistant S. aureus (MRSA) clones. The aac(6')/aph(2'') was the most prevalent (47.8%) AME-encoding gene in aminoglycoside-resistant S. aureus, followed by ant(4')-Ia (30.4%) and aph(3')-IIIa (21.7%).
Conclusion:Our study demonstrated that the coexistence of several AMEs and the spread of the resistance determinants like femA in S. aureus clinical isolates are alarming and may contribute to the broadening of aminoglycoside resistance spectra and limit treatment options for staphylococcal infections.

Abstract Ewing sarcoma (ES) of the head and Neck is a rare entity. The most common location for ES is long bones accounting for 58%, with head and neck accounting only for 3% of all the sites. Here we highlight a unique presentation of ES involving the maxillary region in a 21-year-old male. Patient presented with right maxillary swelling for the last 2 months. Imaging studies reveal osteolytic lesion involving the right maxilla. Ewing's sarcoma rarely affects the head and neck region, posing diagnostic challenges as it mimics many common lesions. Accurate diagnosis requires a multidisciplinary approach involving clinical, radiological, histopathological, and molecular evaluations.

Abstract Background & Objective: Obesity is a growing public health problem worldwide. Bariatric surgery is considered the safest and most effective therapeutic option, although it is associated with various metabolic and neurohormonal consequences. This study aims to evaluate the effect of sleeve gastrectomy (SG) on hypothyroidism within one year following surgery.
Methods: In this single-center prospective cross-sectional study, patients with morbid obesity who were candidates for SG were included. Body mass index (BMI), levothyroxine dosage, and thyroid function tests were compared at baseline and 12 months after surgery.
Results & Conclusion: Patients’ BMI, levothyroxine dosage, TSH, and T4 levels decreased significantly after surgery (P<0.0001). The effect of SG on T3 levels was not statistically significant. The results of this study demonstrate that SG can significantly improve thyroid function tests in patients with morbid obesity and reduce their need for levothyroxine within one year following surgery. 

Abstract Dear Editor,
Mucopolysaccharidosis IVA (Morquio syndrome) is a cause of morbidity in early or late childhood, depending on disease severity. It is an autosomal recessive disorder characterized by short stature and multiple skeletal abnormalities. A deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity, due to mutations in the GALNS gene, leads to the accumulation of keratan sulfate, which destroys cartilage tissue before epiphyseal closure (1). Moreover, respiratory compromise, as well as cardiac, ocular, dental, hearing, and neurologic impairments, are consequences of disease progression (2, 3).

Abstract Dear Editor,
 
Recently, we had the pleasure of reviewing a paper entitled "p53 IHC Result as a Prognostic Tool in MDS," authored by Rezvani et al. and published in your July 2023 edition. The study investigated p53 protein expression in myelodysplastic syndrome (MDS) to better prognosticate patient outcomes. While the results provide strong evidence for p53 protein expression as an adjunct to prognosticate survival in MDS, there are certain considerations that merit closer inspection and discussion.
Important findings necessitate that fellow researchers replicate studies. However, the lack of certain methodological details in this study makes such efforts challenging. Firstly, the paper states that p53 analysis was “carried out according to the standard protocol.” A declaration such as this warrants, at a minimum, citation(s) referring to a ‘standard protocol.’ The authors discuss how prior studies have applied different percentage cutoffs when analyzing p53 expression in bone marrow. The application of a 1% threshold to differentiate between “positive” and “negative” p53 expressors in this context may appear arbitrary without a thorough explanation of how the authors agreed to this specific cutoff. If the threshold was data-driven by the study findings, this needs to be stated clearly. Critics may otherwise rightfully ask what the IHC analysis shows if a 2%, 5%, or higher cutoff is applied instead. Furthermore, p53 IHC staining inherently involves various degrees of nuclear intensity (i.e., 1+ light, 2+ medium, 3+ maximum), which may have implications independent of percentage expression, as has been shown in other organ systems, including the prostate (1–3). While nuclear intensity does tend to correlate with percentage expression, failure to address the intensity in this context invites valid criticism when calibrating a threshold. For example, it remains unclear whether light (1+) intensity nuclei are incorporated into the final, total percentage, as low-intensity nuclei are arguably not “overexpressed” per se (1, 2). Alternatively, is the cell count limited to only nuclei exhibiting maximum (3+) intensity? Clarifying this distinction is essential for accurate interpretation.
In the context of acute myeloid leukemia (AML), it has been demonstrated that p53 protein expression serves as an indicator for detecting TP53 mutations. p53 immunohistochemistry (IHC) has been validated as a rapid, cost-effective tool for identifying impactful TP53 mutations in AML, with a proposed 7.2% cutoff for p53-high as a key indicator, utilizing digital image analysis. Based on this observation, Tashakori et al. proposed a 10% or higher cutoff to consider p53 IHC staining as positive for reflecting TP53 gene mutations, which is significantly higher than the 1% cutoff used in this paper (4).
Additionally, it would have been valuable if the authors had included representative histomorphological images of p53-expressing bone marrow cells in their publication. As the age-old adage states, “a picture is worth a thousand words,” and including images may help clarify this methodological point for readers.
While it is true that wild-type p53 expression is short-lived, the sampled cross-sections of tissue reflect a moment in time when the tissue was excised. In other words, the selected area represents a “snapshot” of p53 protein levels that fluctuates over time and explains its inherently patchy expression, even in “normal,” unaltered p53-expressing cells. This observation brings us to another problematic argument presented by the authors during their discussion, best encapsulated by the statement: “The true frequency of TP53 mutations is underestimated, but IHC overexpression of p53 is always a marker for a molecular alteration with a poor prognosis.” While the argument can be made that the true frequency of TP53 mutations is underestimated, declaring that p53 overexpression is always a marker for an underlying molecular alteration is misleading. The paper referenced by the authors (5) to support this claim, in turn, cites a third source that states, “…the IHC detection of p53 protein suggests an underlying mutation in the gene.” These nuances require precise language for a balanced discussion of p53 prognostication in MDS.
Another important consideration is that the survival analyses have shown a notable association between p53 expression status and mortality. The data reveal a statistically significant association between p53 expression and the IPSS-R score, indicating that higher IPSS-R scores are often associated with positive p53 IHC results. To conclusively determine the independent prognostic significance of p53, it is imperative to evaluate the adjusted hazard ratio while controlling for the IPSS-R value.
In conclusion, while the paper addresses an important topic and contributes significantly to the field of MDS pathology, further clarification of the issues raised herein would be highly valuable for its practical implementation.
 
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.
 
Conflict of Interest
The authors declared no conflict of interest.