Clinicopathological Correlation Research Articles

Establishing an effective clinical data collecting tool for optimal evaluation of native and allograft renal biopsies

IntroductionPercutaneous kidney biopsy is the gold standard method to reach a precise diagnosis in most medical kidney diseases, which positively impacts patient care by personalizing the treatment. Accurate diagnosis in the pathology report for medical kidney diseases requires clinicopathological correlation, and clinical data is not always reachable to the nephropathologist. This study aimed to create a standardized, paperless requisition form compatible with medical renal biopsies. MethodsAn initial form was prepared for native and allograft renal biopsies according to the current classification of medical kidney diseases. We invited 33 nephropathologists working in Canadian healthcare institutions to answer survey questions about the need to include a particular aspect of clinical information. According to the responses, we modified the experimental form. Eighty nephrologists were asked to complete a clinical data-collecting form given out as PDF files. The time for completing the form and clinicians’ satisfaction were assessed. ResultsThe experimental form survey was answered by 20 out of 33 nephropathologists (61%) from 14 Canadian healthcare centers. The agreement rate on the questions was from 38.89% to 100.00% (average 83.33% and 77.14% for the native and the allograft section, respectively). Seventeen out of 80 nephrologists and their assistants (21%) responded by completing 22 PDF forms. The time required to finish a PDF form was 10.4 min on average. Nephrologists considered the form time-consuming and suggested making it more clinically relevant. Only seven nephrologists responded to the satisfaction survey; four (57%) were satisfied. ConclusionsMedical information is critical in renal pathology diagnoses. A uniform paperless clinical data requisition form was evolved through an agreement by Canadian nephropathologists.

Abstract P2-11-17: Prognostic value of Trop2 expression levels in non-metastatic triple-negative breast cancer and correlation with other biomarkers

Abstract Background: Since the development of anti Trop2 antibody-drug conjugates (ADC), Trop2 has been validated as a major therapeutic target for antibody-drug conjugates in metastatic triple-negative breast cancer (TNBC). However, very few data have been reported regarding the prognostic implication, or clinicopathological variables, associated with Trop2 expression levels in early TNBC. Our aim was to evaluate Trop2 expression and its prognostic value in a retrospective series of patients with non-metastatic TNBC and a long follow-up, characterized for Basal-like (BL) or molecular apocrine-like (MA) IHC profiles as well as TILs infiltrate, PDL1 expression and PIK3CA/PTEN mutations. Patients and methods: The analysis was performed in a series of 228 patients with non-metastatic TNBC treated in our center between 2002 and 2012 arrayed on 6 TMA. BL and MA profiles were defined as IHC CK5/6 and/or EGFR expression, and Androgen-receptor and FOXA1 IHC expression, respectively. Trop2 expression levels were tested for their association with baseline clinicopathological variables, and for Relapse-Free Survival (RFS) and Overall survival (OS). Trop2 IHC level of expression was evaluated using the ENZ-ABS380 mouse monoclonal antibody and the methodology described by Bardia et al. (Annals of Oncology, 2021) to quantify the membrane signal. First, we established a score grid, according to staining intensity (no labeling: 0; weak labeling: 1; moderate labeling: 2; strong labeling: 3). Then, for each sampled core, the percentage of labeled invasive tumor cells in each intensity was reported. The overall membrane expression was then calculated using the H-Score method (3 x % of cells with labeling intensity 3 + 2 x % of cells with intensity 2 + 1 x % of cells with intensity 1). The scores obtained ranged from 0 to 300. Results: Median age was 58.2 years (range 28.5-89.1). 43.9% of tumors were classified pT1 and 63.5% pN0. 83.8% of patients had ductal carcinomas. Histological grade 1-2 represented 22.7% of all tumors. A BL phenotype was observed in 68.1% of cases, and an MA profile in 39.4% of the cases. Adjuvant chemotherapy (ACT) was delivered in 74% of patients. We observed low Trop2 expression (H-Score < 100) in 12.3% of the cases (28/228 samples), moderate Trop2 expression (H-Score 100-200) in 28.9% of the cases (66/228 samples), and strong Trop2 expression (H-Score >200) in 58.8% of the cases (134/228 samples). We only identified 3 tumors without any Trop2 expression. Regarding baseline clinicopathological correlations, Trop2 levels were only found significantly associated with pT stage, pT1 tumors displaying more frequently high Trop2 scores compared to tumors >= pT2 (p=0.002). No significant correlation was found between Trop2 expression levels and HER2 levels (0 vs. 1+/2+), BL or MA status. With a median follow-up of 9.7 years, Trop2 levels were not associated with RFS nor OS in univariate analysis. In multivariate analysis, poor RFS was associated with classical variables in the early TNBC setting: tumors >=T2 stage (Hazard Ratio (HR) 2.13, p=0.02), N+ status (HR 3.51, p< 0.001), while high (>5%) TILs infiltration levels (HR 0.54, p=0.03) and adjuvant chemotherapy use (HR 0.49, p=0.007) were associated with improved RFS. Conclusions: Trop2 is expressed in nearly all early TNBC cases, and Trop2 levels of expression, while associated with T stage, did not impact survival in this population. These results are consistent with the ones reported in the metastatic setting in the ASCENT trial. Trop2 level of expression appearing homogeneous distributed in all the clinicopathological subtypes of TNBC, advocating for the evaluation of combined treatments with anti-Trop2 ADCs and dedicated targeted therapies in specific TNBC subgroups. Citation Format: William Jacot, Marie-Christine Chateau, Simon Thezenas, Séverine Guiu, Nelly Firmin, Florence Boissière-Michot. Prognostic value of Trop2 expression levels in non-metastatic triple-negative breast cancer and correlation with other biomarkers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-17.

Follicular Helper T-Cell-derived Nodal Lymphomas: Study of Histomorphologic, Immunophenotypic, Clinical, and RHOA G17V Mutational Profile.

The study was designed to review the demographic, clinical, and pathologic characteristics of follicular helper T cells (TFH)-derived nodal PTCL in India including angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma (PTCL) with follicular helper T cell phenotype (P-TFH), and follicular T-cell lymphoma with additional immunohistochemistry (IHC) and RHOAG17V mutational analysis, as well as their impact on survival. This retrospective study included 88 cases of PTCL that were reclassified using IHC for TFH markers (PD1, ICOS, BCL6, and CD10) and dendritic-meshwork markers (CD21, CD23). Cases of TFH cell origin were evaluated for RHOAG17V mutation using Sanger sequencing and amplification-refractory mutation system-polymerase chain reaction (PCR) (validated using cloning and quantitative PCR) with detailed clinicopathologic correlation. Extensive re-evaluation with added IHC panel resulted in a total of 19 cases being reclassified, and the final subtypes were AITL (37 cases, 42%), PTCL-not otherwise specified (44, 50%), P-TFH (6, 7%), and follicular T-cell lymphoma (1, 1%). The presence of at least 2 TFH markers (>20% immunopositivity) determined the TFH origin. AITL patients tended to be male and showed increased presence of B-symptoms and hepatosplenomegaly. Histomorphology revealed that 92% of AITL cases had pattern 3 involvement. Sanger sequencing with conventional PCR did not yield any mutation, while RHOAG17V was detected by amplification-refractory mutation system-PCR in AITL (51%, P =0.027) and P-TFH (17%), which was validated with cloning followed by sequencing. Cases of RHOAG17V-mutant AITL had a worse Eastern Cooperative Oncology Group performance status initially but fared better in terms of overall outcome ( P =0.029). Although not specific for AITL, RHOAG17V mutation shows an association with diagnosis and requires sensitive methods for detection due to low-tumor burden. The mutant status of AITL could have prognostic implications and translational relevance.

Mutation Analysis and Clinicopathological Implications of Isocitrate Dehydrogenase 1/2 Mutation in Acute Myeloid Leukemia Patients in North India: A Tertiary Centre Based Study

Acute myeloid leukemia has been classified on the basis of morphology, cytochemistry and genetic profile. IDH gene is an epigenetic modifier whose mutation is involved in pathogenesis of various malignancies. This study was planned to study the prevalence of IDH1/2 mutation in denovo AML cases at a tertiary care Centre in North India and also to study its clinicopathological effect in these cases. We evaluated 60 patients registered at our Centre for diagnosis and treatment of AML. Routine investigations, bone marrow examination, flow cytometry were done followed by PCR and sequencing. Out of the total 60 patients of AML 4(6.7%) patients had IDH1R312 mutation and 5(8.3%) Patients had IDH2R172 mutation. IDH2 R140 mutation was not detected in any sample. IDH mutation was significantly associated with high risk AML group. No significant clinicopathological correlation was seen. In this study significant association was observed between IDH mutation and high risk AML cases. There was no paediatric case with IDH mutation. IDH mutation and AML might have an age related association.

A Single Institution Experience with Solid Pseudopapillary Neoplasm of the Pancreas: Clinicopathological Correlation and Review of the Literature

Introduction: SPN is a rare, low-grade malignancy that accounts for 1-3% of all pancreatic neoplasms and tends to affect young females. It can be asymptomatic or present with abdominal pain, and surgical resection is the only curative treatment. Methods: A retrospective study was conducted on patients with biopsy proven Solid Pseudopapillary Neoplasm (SPN) of the pancreas between January 2016 and June 2021. The study included 14 cases, including 7 resection specimens and 7 biopsies, and was conducted at a tertiary referral center in PakistanResults: All 14 patients were female and ranged in age from 15 to 48 years old, with a mean age of 24. The most common symptom was abdominal pain, and the head of the pancreas was the most common location of the tumor. Tumor size ranged from 5 cm to 18 cm, and one patient had lymph node involvement and two patients had hepatic metastasis. Most patients received surgical treatment, and follow-up information was available for 8 out of the 14 patients, who were all alive with no recurrence or metastasis. Conclusion: Due to its rarity, non-specific clinical presentation, and imaging findings, it can be challenging to diagnose. There is a lack of data on SPN from South Asia, so this study provides valuable insights into the occurrence and treatment of SPN in this region.

Evaluation of Serum Levels of Matrix MetalloProteinase-9 (MMP-9) in Oral Squamous Cell Carcinoma and Its Clinicopathological Correlation.

One of the most prevalent malignancies in India is oral squamous cell carcinoma (OSCC), which is found in more than 90% of cancer cases and has a reduced survival rate of 30%. Matrix metalloproteinases (MMPs) are zinc-containing and calcium-dependent endopeptidases that regulate angiogenesis, migration, and proliferation. MMP-9 in OSCC increases tumor progression through angiogenesis, degrades the basement membrane, and facilitates metastasis by changes in tissue shape. Its overexpression in OSCC has also been shown to have prognostic significance. This study aims to evaluate the serum levels of MMP-9 in OSCC patients and healthy controls and to correlate with its clinicopathological staging. This study included 40 individuals; 20 patients with OSCC and 20 healthy controls. MMP-9 was determined in serum samples utilizing enzyme-linked immunosorbent assays. Descriptive statistics showed that 90% of the patients included in the OSCC groups were above 40 years, and 85% were males. There was a significant increase in the serum level of MMP-9 in OSCC patients compared to healthy controls with a mean difference of +28% (393.21 pg/ml) and asignificant p-value of 0.001. (1365.80 ±236.414 pg/ml vs 973.67 ± 83.416 pg/ml). There was a significant increase in the serum levels of MMP-9 among the tumor stages and nodal involvement with a significant p-value of 0.002 and 0.001. No significant association was found between the age and gender groups in OSCC patients and serum levels of MMP-9. MMP-9 was significantly increased in OSCC when compared to healthy controls. Hence, MMP-9 can be used as a prognostic indicator in assessing tumor staging and nodal involvement.

A Study on Clinicopathological Corelation and Management of Solitary Thyroid Nodule

Background: A solitary nodule is a goiter which, on clinical examination appears to be a single nodule in one lobe of the thyroid with no palpable abnormality elsewhere in the gland. The incidence of solitary nodule in general population in South India is 9%. This study aims to assess the presence of malignancy in patients presenting with solitary thyroid nodule and to evaluate and compare results of various investigative modalities used to diagnose a solitary thyroid nodule and the outcome of management modalities in solitary thyroid nodule. Methods: The present study on clinicopathological correlation and management of solitary thyroid nodule has been conducted on cases admitted and managed in the Department of Surgery at KIMS medical college, Hubli. Prospective analysis of 50 cases of solitary nodule thyroid in the specified period was done. These cases were selected by random sampling method and studied in detail clinically and recorded as per the proforma. Routine investigations and specific investigations including FNAC of the nodule, Thyroid profile, IDL, Plain X-ray neck, USG neck were done in all cases. Special investigations like radio-isotope scanning were not performed as the facilities were not available. All the patients were managed by surgery and diagnosis was confirmed by histo- pathological examination. The patients were grouped according to different variables like age, sex, size of the nodule, site of the nodule, functional thyroid status, FNAC reports and histo-pathological examination reports, then analyzed and compared with the previous similar studies conducted elsewhere. Results: Total of 50 cases of solitary nodule of thyroid studied. The mean age of presentation is 38.5 years. Cases in 3rd to 5th decades constitutes 72% of the cases studied. Out of 50 cases studied 46 were females and 4 were males, and the ratio comes to M:F = 1 : 11.5. Out of 50 cases along with swelling in front of the neck, 3 cases had pain, 3 cases had discomfort .....

Direct immunofluorescence cannot be used solely to differentiate among oral lichen planus, oral lichenoid lesion, and oral epithelial dysplasia

Background/purposeSome red and white lesions may have similar manifestations, making them difficult to be diagnosed. A direct immunofluorescence (DIF) assay can assist in making a final diagnosis of oral lichen planus (OLP). The aim of this study was to evaluate and compare the DIF profile in patients who had the clinical presentations of OLP and were histopathologically diagnosed with OLP, OLL (oral lichenoid lesion), or OED (oral epithelial dysplasia). Materials and methodsThe data were obtained from the medical records of 136 patients with the clinical presentations of OLP. Demographic information, histopathological diagnosis, malignant transformation, and DIF results were collected and analyzed. ResultsIn this study, 117 patients (86.0%) were DIF-positive, while 19 patients (14.0%) were DIF-negative. The highest DIF-positivity rate was in the OLP group (88.9%) followed by the OLL (83.7%), and the OED groups (81%). There were no significant differences in DIF-positivity rate, type of immunoreactants, location, or interpretation among these groups. Shaggy fibrinogen at the basement membrane zone (BMZ) was the most common DIF pattern in all groups. ConclusionThe DIF assay alone cannot be regarded as sufficient evidence for OLP, OLL, and OED differentiation. A histopathological examination is required to determine the presence of epithelial dysplasia or malignancy. To diagnose dysplastic lesions with the clinical manifestations of OLP, careful clinicopathologic correlation is mandatory. Due to the lack of scientific evidence to identify the primary pathology and the ongoing malignancy risk of epithelial dysplasia, meticulous long-term follow-up plays a crucial role in patient management.

Quality of Life Assessment With European Organisation for Research and Treatment of Cancer Questionnaire (Head and Neck Module 43) and Its Clinicopathological Correlation Among Patients Treated for Oral Squamous Cell Carcinoma: An Exploratory Study.

Introduction Oral cancer has a great impact on quality of life (QOL). Many risk factors influence the overall QOL. Our study was performed to evaluate the QOL among patients with oral cancer and to correlate it with age, gender, tobacco usage, and clinicopathological details. Methods We have used the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43) and the Quality of Life Questionnaires for Core 30 (QLQ-C30) among the patients diagnosed with oral cancer after reporting to our institution. The Gpower calculation based on differences between two independent means reported by Meera et al. had a total sample size of 28 with an actual power of 0.9616. Thirty-five patients were included in the present study. Ethical clearance for this study was obtained, and there were no gender or age limits for enrollment. The patient demographic details and case history with relevant treatment information were collected from the DIAS (Dental Information Archival Software) of Saveetha Dental College, Chennai. After obtaining informed consent from the patients, the EORTC QLQ-HN43 and QLQ-C30 questionnaires were given to them. It was used both in Tamil and English. Various domains such as pain, appearance, and oral function were documented. The findings were correlated with clinical and histopathological findings. The collected data were tabulated and statistically analyzed with IBM Statistical Package for the Social Sciences (SPSS) version 20 (IBM Corp., USA). The mean ± SD were calculated for continuous variables, and frequency with percentage was determined for categorical parameters. Results The study included both men (57%) and women (43%)in the age range of 30-70 years, with a mean age of 50 years. Study samples included tobacco users (82%) and non-tobacco users (18%). Out of the 35 patients, 15 patients had lesions involving the buccal mucosa (42%) and 10 involving the tongue (28%). Oral squamous cell carcinoma (OSCC) was the most common type of lesion, and it was mostly treated surgically with resection and excision (82%), or just excision (18%). Seventy percent of our patients underwent reconstruction, while primary closure was done in only 30% of cases. All of the patients underwent neck dissection, including supraomohyoid neck dissection (52%), modified radial neck dissection (40%), and radial neck dissection (8%). Histopathology revealed that 49% had well-differentiated squamous cell carcinoma, 23% had moderately differentiated squamous cell carcinoma, and 28% had poorly differentiated squamous cell carcinoma. Out of the 35 included cases, five patients had died (14%). The primary site was buccal mucosa in all five cases, and surprisingly, three patients also had recurrences post-surgery or post-radiotherapy. We observed that the average rating of overall health and overall QOL at the time of diagnosis was 5.4. After one year of follow-up, the average rating of overall health and overall QOL was found to be 3.4. Conclusion The administration of EORTC QLQ-HN43 was found to be efficacious in our study on patients with OSCC. We could identify baseline data regarding the QOL of our patients treated for OSCC. We have identified critical domains of oral function that need to be focused upon to improve the overall QOL of OSCC patients through adjunctive therapies. We have also identified higher mortality and overall poorer QOL in patients with OSCC involving the buccal mucosa.

Expression of immune checkpoint protein in oral squamous cell carcinoma and its clinicopathological correlation: A tertiary care center cross-sectional study.

Recent evidence suggests that oral squamous cell carcinoma (OSCC) patients who exhibit the immunohistochemical expression of immune checkpoint protein programmed cell death ligand 1 (PD-L1) are more likely to have a poor clinical outcome and may serve as an independent prognostic marker. This study aimed to assess the immunohistochemical expression of immune checkpoint protein PD-L1 in OSCC and its clinicopathological correlation. OSCC cases were included in the study. This was a tertiary care center cross-sectional one-year duration study. Histomorphological diagnosis and immunohistochemical expression of PD-L1 were performed after taking ethical clearance. The statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 21.0 statistical analysis software. A total of 106 cases of OSCC were included in the study. Histologically, the majority of cases (58.5%) were graded as well differentiated, followed by moderately differentiated (58.5%) and poorly differentiated (4.7%), respectively. In PD-L1 immunohistochemical expression, score 1+ was accorded to 37 (34.9%), 2+ was accorded to 31 (29.2%), and score 3+ was accorded to 33 (31.1%) cases. Tumor size, pattern, depth of invasion lymphovascular invasion (LVI), and perineural invasion (PNI) were found to be significantly associated with PD-L1 immunohistochemical scores. We concluded that the immunohistochemical expression of immune checkpoint protein PD-L1 positivity in tumor cells was seen in the majority of the cases (60.37%) in our patient. This suggests that the PD-1 or PD-L1 pathway plays a significant role in tumor immune evasion in OSCC.

Vasculitides and occluding vasculopathies, challenges in recognizing histopathological patterns, and their solutions.

In this review, we propose a classification of vasculitides and occluding vasculopathies using the clinicopathological correlation as the basic process. We use an algorithmic approach with pattern analysis, which allows reliable reporting of microscopic findings. We first differentiate between small and medium vessel vasculitis. Second, we differentiate the subtypes of small- and medium-sized vessels. Finally, we differentiate vasculitides according to the predominant cell type into leukocytoclastic and/or granulomatous vasculitis. Regarding leukocytoclastic vasculitis as a central reaction pattern of cutaneous small/medium vessel vasculitides, its relation or variations may be arranged in a wheel-like order. With respect to occluding vasculopathies, the first two steps are identical to the algorithm of vasculitides, and we finally differentiate according to the time point of the coagulation/reorganization process and the involved inflammatory cells/stromal features. By visualizing the criteria in the style of bar codes, clinical and histological overlaps and differences may become more transparent.

Clinicopathological correlate of urine 8-hydroxydeoxyguanosine levels in patients with prostate biopsy

Clinicopathological correlate of urine 8-hydroxydeoxyguanosine levels in patients with prostate biopsy

Mutation status of full RAS and BRAF in 169 Moroccan patients with colorectal cancer.

216 Background: Morocco has the highest cancer mortality rate in MENA Countries. Colorectal cancer (CRC) is classified as the first digestive cancer and remains a burden in Morocco. According to the data on GLOBOCAN 2020, there were 4324 new CRC patients and 2374 deaths, accounting for 7.3% and 2.8% of all cancers, respectively. Our study aimed to investigate the frequency of the full RAS ( KRAS, NRAS) and BRAF genes in CRC patients from Morocco and their possible associations with clinico-pathological features. Methods: Archived FFPE of 169 CRC patients were screened for KRAS, NRAS and BRAF mutations by Idylla technology. Results: Full RAS mutations were identified in 46.1% (42% in KRAS, 4.1% in NRAS). In KRAS gene, exon 2 mutations accounted for 84.5% (69% in codon 12, 15.5 % in codon 13). Within codon 12, KRAS G12D and G12C were more frequently detected (29.5% and 16.9%, respectively). Detection of KRAS mutations, and particularly G12D and G12C subtypes, are of large significance for CRC patients, have possible therapeutic implications. Within codon 13, the most frequently observed mutation was G13D (15.5 %). Outside exon 2, the mutation rate was 35.1% (8.4% in exon 3 and 26.7% in exon 4). Concurrent KRAS mutations were identified in 8 cases, which suggests that multiple mutations can occur in the same or different codons. In NRAS gene, the mutation rates of exon 2 and 3 were 71.4% and 57.1% respectively. G13V and Q61K were the most common mutations, accounting for 28.6 % of each. Concurrent KRAS mutations were identified in 2 cases. Of the 169 samples, mutations in the BRAF gene at V600E were detected in 3.5%. Combined mutational analysis of KRAS, NRAS and BRAF was able to identify 49.6% of patients with CRC as likely non-responders to anti-EGFR therapy. There was an association between KRAS mutations and age, which were higher in the age group>50 years old (p=0.022). Tumors in the left colon (36.61%) are more likely to harbor mutations in KRAS than the rectum (19.7%) in both sexes. The adenocarcinoma well-differentiated was the most frequent for patients with KRAS mutations (54.9%). No significant clinicopathologic correlations with NRAS and BRAF mutations were identified. Conclusions: Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology in Morocco. This approach may be able to significantly reduce the burden of disease in the country. Moreover, the Moroccan government should develop policy on CRC prevention and public health programs which may serve as a feasible setting to increase public awareness on lifestyle risk factors.

Metastatic malignant Brenner tumour in a cervical lymph node – a case report

Background: Malignant Brenner tumour (MBT) is a rare ovarian epithelial malignancy that accounts for <0.05% of all ovarian neoplasms. Most cases are limited to the ovary and fallopian tube and lymph node metastasis is uncommon. Aims: We present a case of a 65-year-old woman who was diagnosed with metastatic MBT in a supraclavicular lymph node. Methods: She was initially diagnosed 6 years earlier with ovarian MBT and managed with total abdominal hysterectomy with bilateral salpingo-oophorectomy but declined adjuvant chemotherapy. She was investigated earlier this year for a 1-month history of neck mass. Results: The core biopsy of the neck mass was misdiagnosed as squamous cell carcinoma with focal keratinisation. The slides of the original resection which diagnosed MBT were reviewed in conjunction with the neck mass biopsy and showed similar appearance and immunohistochemical stain profile (p40 and GATA3 positivity). Therefore, the diagnosis was corrected to metastatic MBT following consideration of the overall clinical context and previous pathology. Discussion: This case highlights the importance of clinicopathological correlation and review of relevant previous specimens to ensure accurate diagnoses and optimal clinical management for patients.

An Immunohistochemical Study on Ki-67 Expression in Squamous Cell Carcinomas of Cervix With Clinicopathological Correlation.

Background Cervical carcinoma is one of the most prevalent cancers affecting women worldwide. Studies on Ki-67 expression in cervical lesions had focused mainly on the intraepithelial lesions of the cervix and not much on invasive carcinomas. The few studies published so far on Ki-67 expression in invasive cervical carcinomas have shown inconsistent results on the association of Ki-67 with various clinicopathological prognostic factors. Aims and objectives To assess Ki-67 expression in cervical carcinomas and to compare it with various clinicopathological prognostic factors. Materials and methods Fifty cases of invasive squamous cell carcinoma (SCC) were included in the study. Histological patterns and grades were identified and noted in these cases after microscopic examination of the histological sections. Immunohistochemical (IHC) staining with anti-Ki-67 was done and scored from 1+ to 3+. This score was compared with clinicopathological prognostic factors like clinical stage, histological pattern, and grade. Result Among the 50 cases of SCC, 41 showed keratinizing pattern (82%) and nine showed non-keratinizing pattern (18%). Four were in stage I, 25 were in stage II, and 21 were in stage III. Overall, 34 (68%) cases had Ki-67 score 3+, 11 (22%) had Ki-67 score 2+, and five (10%) had Ki-67 score 1+. Ki-67 score of 3+ was the most common score in keratinizing SCC (75.6%), poorly differentiated carcinomas (76.2%), and stage III cases (81%). Conclusion We observed statistically significant correlation of Ki-67 expression with higher clinical stage, keratinizing tumours, and poorly differentiated tumours (p<0.05) indirectly implying the poor prognostic significance of this marker.

A Clinicopathological Classification Of Encephalocoeles Based On 207 Patients

Encephalocoeles are relatively rare congenital abnormalities. There have been a few classifications of encephalocoeles, but these are predominantly anatomical. A more clinical classification system would assist in planning treatment, surgical procedures and assessing outcomes. All encephalocoeles presenting at the Craniofacial Unit at Inkosi Albert Luthuli Central Hospital were reviewed. There were 207 patients with 224 encephalocoeles. The clinical presentation and CT findings were analysed and used to group these encephalocoeles. There were five distinct groups with some having subgroups.1.Cranial (n= 43). These were located on the calvarium and were subdivided into subgroups according to their anatomical location. They are occipital, parietal, frontal, temporal and acrania.2.Nasal (n= 122). These were located in the nasal region and were classified into two large subgroups (supranasal and infranasal) depending on whether the pathway and defect were above or below the nasal bones.3.Orbital (n= 21). These presented with the displacement of the globe and were subdivided into two subgroups: anterior and posterior.4.Basal (n= 11). The pathway of these encephalocoeles was through the floor of the anterior cranial fossa often with no visible deformity of the face.5.Cleft related (n= 27). The pathway of these encephalocoeles was through an existing craniofacial cleft. This classification system demonstrated good clinicopathological correlation. This allowed one to better appreciate the pathway and assess concomitant deformities. It also directed one to plan the procedure and detail the surgical corrections required to produce satisfactory outcomes.

Umbilicated vesicles and multiple pustules on the genital area in a man

Umbilicated vesicles and multiple pustules on the genital area in a man

Midline 1 interacting protein 1 promotes cancer metastasis through FOS-like 1-mediated matrix metalloproteinase 9 signaling in HCC.

Understanding the mechanisms of HCC progression and metastasis is crucial to improve early diagnosis and treatment. This study aimed to identify key molecular targets involved in HCC metastasis. Using whole-transcriptome sequencing of patients' HCCs, we identified and validated midline 1 interacting protein 1 (MID1IP1) as one of the most significantly upregulated genes in metastatic HCCs, suggesting its potential role in HCC metastasis. Clinicopathological correlation demonstrated that MID1IP1 upregulation significantly correlated with more aggressive tumor phenotypes and poorer patient overall survival rates. Functionally, overexpression of MID1IP1 significantly promoted the migratory and invasive abilities and enhanced the sphere-forming ability and expression of cancer stemness-related genes of HCC cells, whereas its stable knockdown abrogated these effects. Perturbation of MID1IP1 led to significant tumor shrinkage and reduced pulmonary metastases in an orthotopic liver injection mouse model and reduced pulmonary metastases in a tail-vein injection model in vivo . Mechanistically, SP1 transcriptional factor was found to be an upstream driver of MID1IP1 transcription. Furthermore, transcriptomic sequencing on MID1IP1-overexpressing HCC cells identified FOS-like 1 (FRA1) as a critical downstream mediator of MID1IP1. MID1IP1 upregulated FRA1 to subsequently promote its transcriptional activity and extracellular matrix degradation activity of matrix metalloproteinase MMP9, while knockdown of FRA1 effectively abolished the MID1IP1-induced migratory and invasive abilities. Our study identified MID1IP1 as a regulator in promoting FRA1-mediated-MMP9 signaling and demonstrated its role in HCC metastasis. Targeting MID1IP1-mediated FRA1 pathway may serve as a potential therapeutic strategy against HCC progression.

Expression of Her-2/NEU in Patients With Primary Non-small Cell Lung Cancer (Nsclc)

Introduction: Now a days immunohistochemistry and genomic testing for patient with Non- Small Cell Lung Cancer (NSCLC) is becoming new standard of care in clinical decision making. A renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Aim of this present study was clinicopathological correlation of HER-2/neu expression by IHC in NSCLC. Method: This was a Cross sectional and observational study done at Sir Salimullah Medical College and National Institute of Disease of the Chest and Hospital (NIDCH) and other private hospitals in Dhaka city during July / 2014 to June / 2016. Adult of both gender with histologically diagnosed as a case of NSCLC was include in the study. Immunohistochemistry was done to see the positivity for HER/neu and clinical characteristics were observed. Result: A total 45 patients with NSCLC were enrolled in the study. Male was 77.8% (n=35) and female was 22.2% (n=10). The mean age was 55.67 (SD± 12) years and mean age of male was higher compared to female (57.54±11.64 years verses 49.1±11.38 years). Most of the male were smokers (71.1%) and female were nonsmokers (90%). 57.78% (n=26) of patients and 42.22% (n=19) of patients had adenocarcinoma and squamous cell carcinoma respectively. Most squamous cell carcinoma patients were elderly, had wasting and having higher TNM staging. Serum LDH level was higher with advance staging and grading. Only 8.89% (n=4) had HER-2/neu positive expression affected by male. Patients with HER 2/neu positive expression were relatively older (mean age 62.5±17.08). However, there were equal in histopathological categorization (50% SCC and 50% Adenocarcinoma). Mean LDH was slightly higher in HER-2 positive patients was compared to HER-2 negative patients (569.5±232.6 versus 469.7±181.8). Conclusion: About nine percent of patients having HER-2/neu positive was relatively older and had more high level of LDH. A large-scale study should be conducted in Bangladeshi population to characterize epidemiological, clinicopathological feature in patients with NSCLC with HER-2 expression. J Dhaka Med Coll. 2021; 29(1): 99-110

Late Onset Pseudolymphomatous Reaction to Blue Tattoo Pigment Precipitated by Covid Vaccination

Tattoos can lead to a variety of cutaneous conditions such as allergic or contact dermatitis, lichenoid dermatitis, pseudolymphomatous reactions and granulomatous responses such as foreign body granulomas that may have a sarcoidal histology simulating sarcoidosis.[1] Pseudolymphomatous reactions are less common and may clinically and histologically resemble cutaneous lymphomas. Pseudolymphomatous reactions may develop in response to injections, Borrelia infections and arthropod bites. Diagnosis of cutaneous pseudolymphoma is usually based on clinicopathologic correlation coupled with skin biopsy and ancillary tests such as immunoperoxidase stains and genetic testing when necessary. Treatment is generally successful with application of topical corticosteroid preparation or injection of intralesional corticosteroids and in some cases, surgical excision. Here, we describe the case of a 61-year-old male who presented with 3-4 mm papules contained within the blue region of a multicolored tattoo on his upper right arm that had been present for several years. The reaction developed shortly following a Covid vaccination.