Significance of Estrogen/Progesterone Receptor Expression in Metaplastic Breast Carcinoma.

Introduction: Metaplastic breast carcinoma (MBC) is a rare subgroup of breast neoplasms associated with adverse outcomes because of its aggressive nature. Typically, MBCs show triple-negative hormone receptor (HR) status. Determining the HR status of breast cancer is an integral part because it is an important prognostic factor and helps in the treatment course of the disease. This study aimed to determine the HR status of MBC, its significance, and its association with various clinicopathological parameters. Methods: This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital. A total of 140 biopsy-proven cases of MBC were enrolled in the study. Clinical and pathological data were retrieved from the institutes' archives. Immunohistochemical studies were conducted to determine the estrogen receptor (ER) and progesterone receptor (PR) status. Results: The mean age of MBC in our population was found to be 52.18 ± 12.19 years. The HR positivity rate in our population was found to be 32.9%. A significant association was found between HR status and tumor laterality, tumor size, tumor grade, tumor stage, and recurrence. ER/PR-negative MBCs were most probably associated with higher grade and higher tumor stage and were larger in size (6.62 ± 3.43 cm) than ER/PR-positive MBCs (4.20 ± 1.88 cm). Moreover, ER/PR-positive MBCs showed a higher recurrence rate than ER/PR-negative MBCs (43.5% vs. 25.5%, respectively). No statistically significant relationship was found between HR status and patient age, histological subtype, or survival rate. Conclusion: MBC is a rare breast neoplasm. MBC was found to be triple negative in most cases, but a significant percentage were HR (ER/PR) positive. Moreover, we found an association between HR status and various clinicopathological features, indicating that HR status is a significant predictor of MBC prognosis.

Diagnostic accuracy of intraoperative frozen section for margin evaluation of oral cavity squamous cell carcinoma.

OBJECTIVES: Intraoperative frozen-section evaluation is a valuable technique for detecting positive margins intraoperatively for oral squamous cell carcinoma. We conducted this study to determine the diagnostic accuracy of frozen section in detecting margin status and the effect of tumor grade and stage on diagnostic accuracy. RESULTS: A total of 251 biopsy-proven cases of oral squamous cell carcinoma were included in this study. The tissue specimen resected during surgery was sent to the laboratory for frozen section evaluation. The frozen section results were then compared with the permanent section results to determine the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. The mean age of the patients included in the study was 51.65 ± 10.03 years, with male predominance (55.4%). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of frozen section were 88.81%, 94.84%, 95.20%, 88.10%, and 91.63%, respectively. We conclude that frozen section is a useful technique in determining the margin status intraoperatively in oral cancers, with high diagnostic accuracy. Moreover, certain clinical parameters such as age, gender, disease duration, and tumor stage and grade appear to affect the diagnostic accuracy of frozen section.

Clinicopathological Parameters Predicting Malignancy in Phyllodes Tumor of the Breast.

Introduction Phyllodes tumor (PT) is an uncommon fibroepithelial neoplasm of the breast. It is a biphasic tumor with stromal and epithelial components, with a tendency to recur. Because of its wide range of disease manifestations, it has been subclassified into three categories, i.e., benign, borderline, and malignant, based on several histological parameters. This study was conducted to evaluate the clinicopathological features associated with malignancy in breast PTs. Methods We conducted a retrospective study at the Department of Histopathology at Liaquat National Hospital, Karachi, Pakistan. A total of 146 biopsy-proven cases of PTs were enrolled in the study. Clinical data were obtained from the clinical referral forms. Specimens were obtained from either lumpectomy or simple mastectomy. The specimens obtained were received at the laboratory where after gross examination, paraffin-embedded tissue blocks were prepared, which were sectioned, stained, and studied by a senior histopathologist. Pathological features, such as mitotic count, necrosis, stromal atypia, stromal overgrowth, and heterologous elements, were observed. Based on these features, the PTs were classified into benign, borderline, and malignant tumors. Results The mean age of the PTs in our setup was 40.65 ± 12.17 years with a mean size of 9.40 ± 6.49 cm. Malignant PT was found to be the most prevalent in our population, accounting for 63 (43.2%) cases, followed by borderline (51, 34.9%) and benign (32, 21.9%). A significant association was found between the tumor subtype and patient age, i.e., patients diagnosed with malignant and borderline PTs were found to be of older age (mean 42.82 ± 12.94 and 42.05 ± 11.31 years, respectively) than those diagnosed with benign PTs (mean age 34.12 ± 9.75 years). Moreover, malignant PTs were associated with larger tumor size (mean 11.46 ± 6.08) compared with the other two subtypes. Conclusion We found a significant association among patient age, tumor size, and PT subtype. Therefore, apart from the usual histological parameters, patient age and tumor size are important parameters for predicting the behavior of breast PT and should be considered for management.

Mismatch Repair Deficient (dMMR) Colorectal Carcinoma in a Pakistani Cohort: Association With Clinical and Pathological Parameters.

Introduction Microsatellite instability (MSI) is an important pathway in colorectal carcinoma (CRC) pathogenesis. MSI occurs due to mutations in mismatch repair (MMR) genes that include MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). CRC with MSI is termed MMR deficient (dMMR) CRC. Conversely, CRC with intact MMR genes is called microsatellite stable (MSS) or MMR proficient (pMMR). In this study, we compared the clinicopathological features of dMMR CRC with pMMR CRC. Methods It was a retrospective study conducted in the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, from March 2020 to February 2022, over a duration of two years. Biopsy-proven cases of CRC with upfront surgical resection were included in the study. Microscopic examination was performed to evaluate tumor type, grade, and extent of invasion, presence of necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), peritumoral lymphocytes (PTL), intratumoral lymphocytes (ITL), and nodal metastasis. Immunohistochemical staining was performed using antibodies, namely, MLH1, PMS2, MSH2, and MSH6. Any loss of nuclear expression in tumor cells was termed dMMR or microsatellite instable, whereas the intact nuclear expression in tumor cells was labeled as MSS or pMMR. Results A total of 135 cases of CRC were included in the study. The mean age at diagnosis was 46.76 ± 17.74 years, with female predominance (60.7%). The loss of MLH1, PMS2, MSH2, and MSH6 expression was noted in 39.3%, 34.1%, 17.8%, and 16.3% cases, respectively. Overall, 59.3% of CRCs were pMMR, while 40.7% were dMMR. A significant association of MMR status was noted with respect to age, PNI, LVI, tumor grade, tumor (T) and nodal (N) stage, mucinous differentiation, and ITL. dMMR CRC was significantly above 50 years than pMMR CRC. The frequency of PNI and LVI was lower in dMMR CRC than in pMMR CRC. Conversely, the higher grade (grade 3) and higher T-stage (T4) were associated with dMMR CRC. Alternatively, the frequency of higher N stage (N2b) was more commonly seen in pMMR CRC. Moreover, mucinous differentiation and ITL were significantly associated with dMMR CRC. Conclusion A significant proportion of CRC patients in our population demonstrated dMMR status. dMMR CRC had a higher histological grade with a higher frequency of mucinous differentiation and higher T-stage. Conversely, the presence of LVI, PNI, and higher N stages were associated with pMMR CRC.

Early-Onset/Young-Onset Colorectal Carcinoma: A Comparative Analysis of Morphological Features and Biomarker Profile.

Introduction Colorectal carcinoma (CRC) is one of the most common cancers that involve the human body. Young-onset CRC (YO-CRC) or early-onset CRC (EO-CRC) is defined as CRC that develops before the age of 50 years, as opposed to CRC that is diagnosed after the age of 50, referred to as late-onset CRC (LO-CRC). EO-CRC is sparsely studied in our population. Therefore, in this study, we evaluated the clinicopathological parameters and biomarker profile of EO-CRC and compared them with those of LO-CRC. Methods This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan. A total of 254 biopsy-proven cases of CRC, reported over a period of nine years, were enrolled in the study. The specimens collected during surgery were sent to the laboratory for histopathological and immunohistochemical (IHC) status examinations. IHC staining of the specimens was performed using antibodies, namely, MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and human epidermal growth factor receptor 2 (HER2/neu), on representative tissue blocks. A comparison of morphological and biomarker profiles between EO-CRC and LO-CRC was performed. Results The mean age at diagnosis was 46.27±17.75 years, with female predominance (59.8%). A significant difference between the two groups (EO-CRC and LO-CRC) was noted with respect to laterality, tumor site, tumor grade, tumor type, presence of pre-existing polyps, perineural invasion (PNI), lymphovascular invasion (LVI), and IHC markers. EO-CRC (as opposed to LO-CRC) significantly affected the left colon (92.6% vs. 72.9%, p<0.001), with the rectosigmoid being the most common site in the majority of cases (72.1% in EO-CRC vs. 61% in LO-CRC). EO-CRC showed a higher frequency of PNI and LVI than LO-CRC (42.6% vs. 23.7%, p=0.001; 29.4% vs. 18.6%, p=0.046, respectively). A significantly higher proportion of EO-CRCs were mucinous (42.6%) and medullary carcinoma (11.8%). Although the majority (54.4%) of cases of EO-CRC were grade 2 tumors at the time of diagnosis, a significantly higher proportion of them were grade 3 (44.1%) compared with LO-CRC. IHC comparisons between the two age groups showed that a significantly higher proportion of cases of EO-CRC showed positive HER2/neu expression (27.1%) compared with LO-CRC (13.2%). Conversely, the loss of expression of microsatellite instability (MSI) markers was more commonly seen in LO-CRS compared with EO-CRC. Conclusions We found a relatively higher frequency of EO-CRC in our population. Moreover, compared with LO-CRCs, EO-CRCs were associated with prognostically poor histological parameters, such as mucinous and medullary carcinoma, high-grade, PNI, and LVI. Similarly, EO-CRC had a higher positive expression of HER2/neu with intact MSI markers compared with AO-CRC; all these characteristics indicate poor biological behavior in EO-CRC.

Clinicopathological Parameters and Biomarker Profile in a Cohort of Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).

INTRODUCTION:  Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck region, commonly termed as head and neck squamous cell carcinoma (HNSCC). Data related to biomarker expression in HNSCC are scarcely available, especially in our population. This study aimed to evaluate the association of immunohistochemical (IHC) expression of p16, epidermal growth factor receptor (EGFR), p27, and p53 in HNSCC with clinical and pathological parameters. METHODS:  This retrospective cross-sectional study was conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan from February 2017 to January 2022. A total of 308 cases of HNSCC with upfront surgical resection were included in the study. IHC analysis was performed for EGFR, p16, p27, and p53, and association with clinicopathological parameters was sought. RESULTS:  p16, EGFR, and p53 positivity were noted in 22.1%, 18.8%, and 66.2% cases, respectively, whereas loss of p27 expression was seen in 14.3% cases of HNSCC. A significant association of p16 expression was observed with age, tumor size, tumor site, nodal metastasis, extranodal extension (ENE), and perineural invasion (PNI). Cases aged over 50 years were more significantly associated with positive p16. Similarly, cases with oral cavity SCC were more significantly associated with positive p16. HNSCC with larger tumor size, the presence of nodal metastasis, and ENE and PNI were associated with negative p16 expression. Similarly, a significant association of EGFR expression was observed with age, tumor size, tumor site, histological subtype, histological differentiation, nodal metastasis, ENE, and PNI (p < 0.05). Cases of HNSCC with age less than 50 years were associated with positive EGFR expression. Similarly, oral cavity and lip SCCs were associated with positive EGFR expression compared with other sites. Moreover, positive EGFR expression was significantly associated with nodal metastasis, ENE, moderate histological differentiation, and the presence of PNI. Loss of p27 expression was significantly associated with nodal stage and ENE; low nodal stage and absence of ENE were associated with p27 loss of expression, whereas no significant association was seen with other pathological parameters. Alternatively, a significant association of mutant-type p53 expression was noted with gender, nodal stage, and histological subtype. Females with HNSCC show a higher frequency of mutant-type p53 expression than males. Moreover, higher nodal stage (N2b and higher) and non-keratinizing SCCs were significantly associated with mutant-type p53 expression. CONCLUSION:  Our study found a high expression of EGFR and mutant-type p53 expression in HNSCC. Conversely, p16 expression and loss of p27 expression were low. Moreover, EGFR and mutant-type p53 expression were associated with poor pathological parameters, whereas p16 expression was associated with better histological features.

Luminal B, Human Epidermal Growth Factor Receptor 2 (HER2/neu), and Triple-Negative Breast Cancers Associated With a Better Chemotherapy Response Than Luminal A Breast Cancers in Postneoadjuvant Settings.

Background Breast cancer is a heterogeneous disease with many histological and molecular/intrinsic breast cancer subtypes. Intrinsic breast cancer subtypes include luminal A, luminal B, human epidermal growth factor receptor 2 (HER2/neu), and triple-negative subtypes. The intrinsic breast cancer typing is based on the expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki67-labeling index. One of these patients' foremost prognostic factors upon surgical resection is a response to neoadjuvant chemotherapy. The presence of a pathologically complete response (pCR) indicates a favorable patient outcome compared with a pathologically partial response (pPR). In this study, we compared the neoadjuvant chemotherapy response in breast cancer in different intrinsic breast cancer subtypes. Methodology It was a retrospective cross-sectional study conducted in the Department of Histopathology, Liaquat National Hospital, from January 2019 to December 2022, over three years. A total of 287 post-neoadjuvant chemotherapy cases of breast cancer were included. Anthracyclines and taxanes, coupled with or without anti-HER2/neu therapy, have been used in the neoadjuvant chemotherapy treatment setting contingent upon the patients' HER2/neu status. The post-chemotherapy response was assessed pathologically and categorized into pCR and pPR. Results The mean age of the patients was 47.90 ± 10.34 years, with a mean tumor size and Ki67 index of 5.36 ± 2.59 cm and 36.30 ± 22.14%, respectively. Invasive breast carcinoma of no special type (IBC-NST) made up 88.2% of cases, while grade 2 carcinomas made up 45.5%. The majority of tumors (42.7%) belonged to tumor (T) stage T2, and nodal metastasis was detected in 59.7% of patients. The intrinsic breast cancer subtypes luminal B (40.6%) and triple negative (33.3%) were the most prevalent, followed by luminal A (15.8%) and HER2/neu (10.3%). In 81 cases (24.5%), pCR was detected. The association of post-neoadjuvant chemotherapy response with intrinsic breast cancer subtypes showed a significant difference (P < 0.001). The highest frequency of pCR was noted in HER2/neu cancers (58.8%), followed by luminal B (25.4%) and triple negative (23.6%). Regarding age, T-stage, tumor grade, and histological type of carcinoma, there was no discernible difference between pCR and pPR. Conversely, a significant association was noted for the Ki67 index. A Ki67 index higher than 25% showed a significantly higher frequency of pCR. Conclusions In postchemotherapy specimens, the HER2/neu breast cancer subtype substantially displayed higher pCR, followed by luminal B and triple-negative subtypes. After identifying the patients' subtypes, intrinsic subtyping can help determine the prognosis and anticipated response to chemotherapy. Furthermore, prechemotherapy breast specimens with high Ki67 index values have shown a direct association with neoadjuvant chemotherapy response.

Clinicopathological Parameters Predicting Nodal Metastasis in Head and Neck Squamous Cell Carcinoma.

Introduction Squamous cell carcinoma (SCC) is the most common type of malignancy of the head and neck region arising from the mucosal epithelium of the oral cavity and oropharynx. It is a multifactorial disease with a high rate of mortality. Lymph node metastasis is an important prognostic parameter associated with adverse prognosis. This study was conducted to establish a relationship between various clinicopathological characteristics and nodal metastasis in head and neck squamous cell carcinoma (HNSCC). Methods This retrospective study was conducted at Liaquat National Hospital, Karachi, Pakistan. A total of 306 biopsy-proven cases of HNSCC were included in the study. Clinical data, which included age, sex, and site of the lesion, were obtained from the clinical referral forms. Resections of the lesions were performed, and the specimens collected were sent to the laboratory for histological evaluation. The histological subtype, perineural invasion (PNI), depth of invasion (DOI), nodal metastasis, and extranodal extension were assessed, and the association of clinicopathological parameters with nodal metastasis was sought.  Results The mean age at diagnosis was 50.26 ± 12.86 years with a female predominance (55.27%), and the mean tumor size was 3.37 ± 1.75 cm. The mean DOI was 1.08 ± 0.67 cm. The most common site of tumor was found to be the oral cavity (68.6%), followed by the tongue (24.2%). Keratinizing SCC (59.5%) was found to be the most prevalent histological subtype. At the time of diagnosis, the majority of the tumors were grade 2 (62.4%). PNI was present in 12.1% of the cases. Nodal metastasis was present in 44.8%, and extranodal extension was present in 17% of the cases. A significant association of nodal metastasis was noted with age, gender, tumor site, tumor size, and DOI. Male patients with HNSCC showed a higher frequency of nodal metastasis than female patients. Patients between the ages of 31 and 50 years with a tumor size of above 4 cm and a DOI of more than 1 cm had a higher frequency of nodal metastasis. Similarly, tumors arising in the oral cavity and the keratinizing subtype were more likely to possess nodal metastasis. Conclusion We found that HNSCCs were more prevalent among the female population, with the most common site being the oral cavity. Nodal metastasis was significantly associated with the keratinizing subtype of SCC, oral cavity location, male gender, and middle age group. Similarly, the tumor size and DOI were important predictors of nodal metastasis in HNSCC in our study.

Clinicopathological Profile of a Cohort of Patients With Malignant Melanoma in the United Kingdom.

Introduction Malignant melanoma (MM) is potentially a fatal type of skin cancer and a major health concern for the Caucasian population. It is a heterogeneous disease with a wide spectrum of manifestations. Therefore, in this study, we evaluated the clinicopathological characteristics of MM. Methods We retrospectively studied the clinicopathological characteristics of MM in 167 biopsy-proven cases of MM reported between January 2020 and December 2021 at Kings Mill Hospital, Sutton-in-Ashfield, United Kingdom. Clinical data such as the age, sex, and anatomical site of the lesion were obtained from the clinical referral forms. Biopsies of the lesions were performed, and the specimens collected were sent to the laboratory for histopathological study and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation evaluation. Formalin-fixed paraffin-embedded blocks (FFPE) were prepared, sectioned, and stained with hematoxylin and eosin for histological examination. Results A total of 167 cases of MM were included in the study. The age range was 23-96 years, with the median age at diagnosis found to be 66 years; males were more commonly affected (52.1%). The median Breslow thickness was 1.20 mm. The median mitotic activity was 1.0/mm2. The lower limb was the most common site of involvement (27.5%), followed by the thorax (25.1%). The most common histological subtype was superficial spreading melanoma (SSM) (77.8%), followed by nodular melanoma (14.4%). The in situ component was present in 95.8% of cases; a majority (92.2%) of the cases showed vertical growth phase, 71.9% of cases were at Clark's level IV of invasion, regression was noted in 70.7% of cases, ulceration was present in 21.6% of cases, and microsatellites were present in 3% of cases. Perineural invasion was present in 3% of cases, and lymphovascular invasion (LVI) was present in 4.2% of cases. BRAF mutation testing was performed on 36 cases, out of which 20 cases (55.6%) showed BRAF mutation. Acral lentiginous melanoma and nodular melanoma were most likely to show ulceration (66.7% and 37.5%, respectively). SSM and lentigo maligna melanoma were more likely to be associated with regression. Conclusion The study demonstrated that MM is prevalent among the elderly population with male predominance; SSM was found to be the most common subtype. The study further demonstrated various clinicopathological features of MM and its association with histological subtypes.

Clinicopathological Parameters Associated With Peritoneal Involvement in Epithelial Ovarian Tumors.

Introduction Ovarian tumors remain one of the leading malignancies of the female genital tract, with a high mortality rate due to their insidious onset and lack of detection at an earlier stage. These tumors metastasize by direct extension into the neighboring pelvic organs; hence, the detection of peritoneal metastasis is valuable for staging and prognostic purposes. Peritoneal wash cytological analysis is an effective predictor of the involvement of the ovarian surface and peritoneal dissemination even in subclinical involvement of the peritoneum. The study aims to determine the significance of peritoneal wash cytology as a prognostic parameter and correlate it with various clinicohistological features. Methods A retrospective study was conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, between July 2017 and June 2022. During this period, all the cases of ovarian tumors (borderline and malignant) that underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and omental and lymph node sampling were included in the study. After opening the abdominal cavity, the free fluid present was aspirated immediately, the peritoneum was lavaged with 50-100 mL of warm saline, and samples were collected and sent for cytological analysis. Four cytospin smear slides and cell block preparation were prepared. The findings of peritoneal cytology were correlated with various clinicohistological features. Results A total of 118 cases of ovarian tumors were included in the study. Serous carcinoma was the most common sub-type (50.8%), followed by endometrioid carcinoma (14.4%), and the mean age at diagnosis was found to be 49.9±14.9 years. The mean tumor size was 11.2 cm. The majority of the cases of ovarian carcinoma were of high grade (78.8%), with capsular invasion present in 61% of cases. Positive peritoneal cytology was noted in 58.5% of cases, with omental involvement in 52.5% of cases. Serous carcinoma showed the highest frequency of positive cytology (69.6%) and omental metastasis (74.2%). Apart from tumor type, positive peritoneal cytology showed a significantly positive correlation with age, tumor grade, and capsular invasion. Conclusion Based on our study findings, we conclude that peritoneal wash cytology is a sensitive indicator of the peritoneal spread of ovarian carcinoma, with a significant prognostic value. Serous carcinomas, especially high-grade with capsular invasion, were found to be predictors of peritoneal involvement of ovarian tumors. Although we found smaller tumors to be associated with peritoneal disease more compared to larger ones, this most likely is attributed to tumor histology, as larger tumors were most commonly mucinous compared to serous carcinomas.

Aggressive Angiomyxoma, Angiomyofibroblastoma, and Cellular Angiofibroma of the Lower Female Genital Tract: Related Entities With Different Outcomes.

Introduction Mesenchymal tumors of the lower female genital tract (FGT) are a miscellaneous group of tumors that include aggressive angiomyxoma (AAM), angiomyofibroblastoma (AMFB), cellular angiofibroma (CAF), and related entities. Histologically, these tumors are composed of stromal cells admixed with vessels, with some minor histological differences. An accurate diagnosis of these tumors is important owing to the differences in the outcome. In this study, we determined the clinicopathological characteristics of these tumors in our population and their association with recurrence.  Methods This was a retrospective cross-sectional study conducted at the Department of Histopathology, Aga Khan University, from January 2005 to December 2019 over a period of 15 years. A total of 207 cases that were diagnosed as AAM, AMF, and CAF were selected for inclusion in the study. Clinical data, including age and location of the lesion, were obtained from histopathology referral forms. Tissue blocks of all cases were retrieved. Follow-up data were obtained from the patient files, and information regarding disease recurrence was recorded. One histological section from each tissue block was stained with hematoxylin and eosin stain, and histopathological findings were recorded. Additionally, immunohistochemical (IHC) studies, including vimentin, smooth muscle actin (SMA), and desmin were conducted on representative tissue blocks. Final histopathological diagnoses were rendered considering clinical, histopathological, and IHC findings. Results The median age of patients involved in the study was 33 years and the median tumor size was 5 cm with a predilection for the vulva (47.3%). AAM showed a predilection for patients between the ages of 31-45 years, while AMFBs and CAFs were most common in younger age groups of less than 30 years. In 46.8% of cases, the tumor size of AAM was between 6 and 10 cm, while in all cases of CAF (100%) and the majority of AMFB cases (53.2%) the tumor size was smaller than 5 cm. Histologically, in all cases of AAM, the lesional cells were spindle (100%), whereas, in 13% of cases epitheloid cells were observed, with myxoid stroma in 92.2% cases. The presence of stromal smooth muscle was noted in 42.9% of cases, in 79.2% of cases the vessels were thick-walled, with 54.5% having hyalinized vessels, and most of the cases (77.9%) had ill-defined borders. Among IHC findings, AMFB was most frequently positive for actin (62.2%), while AAM and AMFB showed more frequent staining for desmin compared to CAF. A significantly higher recurrence rate was observed in AAM (27.3%), compared to AMFB and CAF. A significant association of recurrence was seen with tumor size. It was noted that the recurrence rate was directly proportional to the size of the tumor and was highest (60%) with a tumor size of more than 10 cm. Conclusion In our study, we noted that AMFB was the most common among the three mesenchymal tumors of the lower FGT. In contrast, AAM had the highest recurrence rate, and recurrence was significantly associated with tumor size. Histological findings, especially the type of stromal cells and background vasculature, are of utmost importance for the correct recognition of these tumors, while the role of IHC studies is limited.

Clinicopathological Features of Alopecia With an Emphasis on Etiology and Histopathological Characteristics of Scarring Alopecia.

Introduction Alopecia is a common dermatological condition with varied etiologies based on age, gender and geographic location. Non-cicatricial (non-scarring) alopecia is more common but often not biopsied. Alternatively, primary cicatricial (scarring) alopecia is diagnostically more challenging and more commonly biopsied to determine the etiology. In this study, we evaluated the clinicopathological characteristics of alopecia in our population. Methods We conducted a retrospective study at the Department of Histopathology, Liaquat National Hospital and Medical College, Pakistan. A total of 104 patients were enrolled in the study who underwent scalp biopsy for alopecia over a period of 11 years. Clinical data were obtained from clinical referral forms, which included age, sex of the patients and duration of the lesions. Three hematoxylin and eosin-stained tissue sections, along with periodic acid-Schiff (PAS), PAS with diastase and collagen stains were examined, and histopathological diagnosis was rendered. Results Our study demonstrated that alopecia was more prevalent among females, accounting for 73.1% of cases. Most of the patients belonged to the age group of <35 years (53.8%). The type of alopecia in 88.5% of the cases was scarring, while there were 11.5% cases of non-scarring alopecia. The most common diagnoses were discoid lupus erythematosus (DLE) (23.1%) and pseudopelade of Brocq (PB) (23.1%), followed by lichen planopilaris (LPP) (15.4%). A significant association was noted between the histological features and the diagnosis, as epidermal atrophy was the most common histological feature in most cases of DLE, followed by periadnexal infiltrates, lymphocytic infiltrates, follicular plugging and basement membrane thickening. In LPP, the most common histological features were perifollicular infiltrates and fibrosis. In PB, the frequently recurring histological features in most cases were the loss of sebaceous glands, dermal fibrosis and epidermal thinning. Conclusion In this study, we demonstrated the key role of skin punch biopsy and histology in determining the accurate etiology of scarring alopecia. We found discoid lupus erythematosus and pseudopelade of Brocq to be the most common causes of scarring alopecia, followed by lichen planopilaris.

Impact of Histological Type and Grade on the Diagnostic Accuracy of Intraoperative Frozen Section for Detecting Breast Cancer Metastasis to Axillary Sentinel Lymph Nodes.

Introduction Intraoperative sentinel lymph node (SLN) evaluation is the standard of care in patients with clinically node-negative breast cancer. The most common histological subtype of breast carcinoma is invasive ductal carcinoma (IDC), followed by invasive lobular carcinoma (ILC). Alternatively, histological grades vary from grades G1 to G3. Therefore, in this study, we evaluated the diagnostic accuracy of frozen section (FS) for detecting breast cancer metastasis to SLNs with respect to histological subtypes and grades. Methods A retrospective observational study was conducted in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, from January 2013 till December 2020, over a duration of eight years. A total of 540 cases of primary breast cancer, undergoing upfront breast surgery were included in the study. Intraoperatively, SLNs were identified and sent for FS. After FS reporting, the remaining tissue was submitted for final (paraffin) section examination after formalin fixation, and results of FS and final (paraffin) sections were compared. Results The mean age of the patients included in the study was 52.05±12.42 years, and the median number of SLNs was three (ranging from one to 14). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of intraoperative FS were 88.2%, 100%, 100%, 92.5%, and 95.2%, respectively. The sensitivity of FS for IDC was 88.3%, whereas it was 85.7% for ILC. Alternatively, the sensitivity of FS for grade G1, G2, and G3 tumors was 78.3%, 91.5%, and 90.2%, respectively. The false-negative rate for grade G1 tumors was 21.7%, which was higher than G2 and G3 tumors (8.5% and 9.8%, respectively). Similarly, the false-negative rate for cases where the number of SLNs was more than three was only 5.4%, which was lower than cases with a single and two to three SLNs sent on FS (23.1 and 14.7%, respectively). Conclusion The sensitivity of intraoperative FS for detecting ILC metastasis to axillary SLNs was not substantially different from IDC; however, histological grade affects the sensitivity of FS diagnosis, with lower-grade tumors having low sensitivity. Moreover, increasing the number of SLNs sent intraoperatively on FS improves the sensitivity of FS for detecting breast cancer metastasis to axillary SLNs.

Mutant Phenotype p53 Immunohistochemical Expression Is Associated With Poor Prognostic Parameters and Disease-Free Survival in Triple-Negative Metaplastic Breast Carcinoma.

Introduction Metaplastic breast carcinoma (MBC) is a special type of breast cancer that is most commonly triple-negative and has the worst outcome compared to other breast tumors. p53 is a tumor suppressor gene that is frequently mutated in many human cancers. The association of mutant p53 immunohistochemical expression with clinical and prognostic parameters has not been widely studied in triple-negative MBC. Therefore, in this study, we evaluated the expression patterns of p53 in triple-negative MBC and its association with clinical and prognostic parameters. Methods A retrospective observational study was conducted in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, for a duration of 11 years. A total of 101 cases of triple-negative MBCs were included in the study. p53 immunohistochemistry was performed on the representative tissue blocks. Cases with diffuse strong positive p53 expression were labeled mutant phenotype, while cases with weak patchy p53 expression were termed wild-type. Results The mean age of the patients was 48.33±11.47 years, and the mean tumor size was 3.98±2.07 cm. The mean Ki67 index was 48.98±22.97%. The median disease-free survival of the patients was 24 (three to 68) months, with a median follow-up of 37 (13 to 77) months. Most of the cases were tumor (T)-stage II (51.5%). Axillary metastasis was present in 36.6% of cases, with the perinodal extension in 16.8% of cases. Most cases were non-basal subtype (91.1%), and the majority of cases were grade III (85.1%). Recurrence was observed in 17.8% of cases. Among 101 cases, 52.5% cases showed mutant phenotype p53 expression. A significant association of p53 expression was noted with tumor grade, Ki67 index and disease-free survival. Cases with mutant phenotype p53 expression had a higher tumor grade, higher Ki67 index, and poorer disease-free survival than cases with wild-type p53 expression. Conclusion A substantial proportion of triple-negative MBC expressed diffuse strong expression (mutant phenotype) of p53 in our study, signifying a potential role of p53 as a therapeutic target in triple-negative MBC. Moreover, association of p53 with poor prognostic parameters, such as higher tumor grade and Ki67, and poor disease-free survival underscores the prognostic significance of p53 in triple-negative MBC.

Triple-Negative Metaplastic Breast Carcinoma: Association of Epidermal Growth Factor Receptor Expression With Prognostic Parameters and Clinical Outcome.

Introduction Metaplastic breast carcinoma (MBC) is one of the rare special subtypes of breast carcinoma associated with poor prognostic features compared with invasive ductal carcinoma. Moreover, therapeutic options are limited in MBC owing to frequent triple-negative profiles of these tumors. Epidermal growth factor receptor (EGFR) is a proto-oncogene that is overexpressed in many human cancers, and is a potential therapeutic target. Therefore, in this study, we evaluated the expression of EGFR in MBC by immunohistochemistry, and its association with clinicopathological and prognostic parameters. Methods We conducted a retrospective observational study in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, over a period of seven years. A total of 61 cases with a histopathological diagnosis of MBC were included in the study. All slides were reviewed by histopathologists for diagnostic confirmation. Histopathological parameters, such as tumor size, grade, and nodal metastasis, were recorded. The representative tissue blocks were also retrieved and immunohistochemical studies were performed for cytokeratin 5/6 (CK5/6), Ki67, and EGFR. Results The mean age of the patients was 44.48 ± 13.01 years. The mean tumor size was 5.72 ± 2.72 cm, with most of the cases belonging to tumor (T)-stage T3. Axillary metastasis was present in 57.4% cases, and the perinodal extension was present in 11.5% cases. Most tumors were grade III (85.2%), with a mean Ki67 index of 39.67% ± 20.38%. Most of the cases were nonbasal (83.6%), owing to the absent CK5/6 expression. Tumor recurrence was noted in 14.8% cases, with a median follow-up of 43 (13-83) months and median disease-free survival of 36 (12-60) months. Positive EGFR expression was noted in 52.5% cases. A significant association of EGFR expression was noted with tumor grade, mean Ki67 index, axillary metastasis, and nodal (N)-stage. Cases with positive EGFR expression were found to have higher grade (grade III), with higher Ki67 index, higher frequency of axillary metastasis, and higher N-stage. Moreover, cases with positive EGFR expression had lower disease-free survival compared to cases with negative EGFR expression. Conclusion We found that a significant proportion of triple-negative MBC expressed EGFR. Moreover, EGFR overexpression was associated with poor pathological parameters and lower disease-free survival. Therefore, EGFR can be considered a potential prognostic biomarker and therapeutic target in triple-negative MBC; however, the correlation between gene amplification and protein overexpression is required to better uncover the role of EGFR as a therapeutic target.

Clinicopathological Features of Craniopharyngioma: A 15-Year Study From a Tertiary Care Center in Pakistan.

Introduction Craniopharyngiomas (CPs) are benign neoplasms and most common suprasellar tumors. They are more frequent in children, contributing to a significant number of intracranial tumors in the pediatric population and are thought to be arising either from the epithelial remnant cells of the craniopharyngeal duct or from the adenohypophysis epithelium. Two subtypes of CPs exist, namely, adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP). ACP is more common in children with a relatively aggressive clinical course and more frequent relapses than PCP. The study objective was to evaluate the clinicopathological features of CP in our population. Methods We conducted a retrospective observational study in the Department of Histopathology at Aga Khan Hospital, Karachi, Pakistan, over a period of 15 years, from January 2001 to December 2015. All CP cases were included in the study. A total of 207 cases were diagnosed during this period by histopathologists based on histologic features. All slides were retrieved, and diagnosis was confirmed after a reexamination of slides. Results We found that the mean age of diagnosis was 25.59±14.71 years, and the median follow-up time was 7 (3-19) years. The number of male patients was 136 (65.7%) and the number of female patients was 71 (34.3%). The most common tumor site was suprasellar (71.5%) followed by the sellar and temporal lobe (12.1% and 6.8%, respectively). The most common complaints were headache (21.7%), followed by loss of vision/decreased vision (16.4%) and vomiting (5.3%). The overall survival rate was 95.2% with a recurrence rate of 5.8%. A significant association of survival was noted with tumor recurrence. Conclusion CP is a rare brain tumor with good overall survival. We found a low recurrence rate of CP in our study. However, recurrence was found to be the most important factor determining survival in patients with CP.

Metaplastic Breast Carcinoma: Clinicopathological Parameters and Prognostic Profile.

Introduction Metaplastic breast carcinoma (MBC) is defined as breast cancer with a heterologous non-glandular component. MBC is considered a special type of breast cancer with a prognosis that is worse than invasive ductal carcinoma (IDC) of the breast. MBC is the most common breast cancer with a triple-negative profile. Therefore, in this study, we evaluated the clinicopathological parameters, recurrence and survival of MBC in our population. Methods We conducted a retrospective observational study in the Department of Histopathology at Prince Faisal Oncology Centre, Buraidah, Saudi Arabia, over a period of five years. All cases diagnosed as MBC were included in the study. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) immunohistochemistry (IHC) was performed on representative tissue blocks. Results Total 183 cases of MBCs were included in the study, out of which 120 cases were excision specimens. The mean age of the patients was 48.84±12.99 years, and the most common age group was between 36 and 50 years of age. Most of the cases were tumor (T) stage T3 (50%), and nodal metastasis was present in 40% of cases. Most cases were grade III (78.7%). ER, PR and HER2/neu positivity was noted in 15.8%, 13.1%, and 9.8% cases, respectively. Follow-up data were available for 70 cases, with a median follow-up period of 4 (1-7) years. Tumor recurrence was noted in 31.4% cases, with a survival rate of 71.4%. Squamous, chondroid, spindle cell differentiation, and matrix production were noted in 70.5%, 7.1%, 13.7%, and 2.2% cases, respectively. A significant association of squamous differentiation was noted with HER2/neu positivity. An inverse association of spindle cell differentiation was seen with axillary metastasis. Survival analysis by Kaplan-Meier revealed a significant association of survival with tumor recurrence. Conclusion MBC is an important subtype of breast cancer, histopathological identification of which is challenging, owing to varied histological differentiation. We found squamous differentiation to be the most common in MBC, which was associated with HER2/neu positivity. A high recurrence rate of MBC was also observed in our study that was significantly associated with survival.

Mucinous Breast Carcinoma: Clinicopathological Comparison With Invasive Ductal Carcinoma.

Introduction Invasive ductal carcinoma (IDC) is the most common histological subtype of breast cancer. Conversely, many special types of breast carcinoma were described with varying prognosis and hormone receptor status. Mucinous carcinoma (MC) is a rare special subtype of breast cancer, and only a few studies have evaluated the clinicopathological and hormone receptor profile of this type of breast cancer. Therefore, in this study, we compared the clinicopathological characteristics of MC with IDC in our population. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2013 till December 2020, for eight years. During this period, 38 cases of MC were diagnosed and 1268 cases of IDC were identified. All specimens were grossed according to standard protocols and representative sections were submitted from tumors, resection margins, and lymph nodes. Slides were examined by histopathologists to determine tumor type and grade. Immunohistochemical (IHC) stains were applied to evaluate estrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2/neu) statuses. Results The mean age of the patients with MC was 56.47±13.90 years, and most of the patients were above 50 years of age. The mean tumor size was 34.89±19.70 mm. Most tumors were grade 1 (68.4%) with a low mean Ki67 index (15.21±14.06%). Axillary metastasis was present in 31.6% of cases and all of them were nodal (N)-stage N1. ER, PR, and HER2/neu positivity were noted in 94.7%, 78.9, and 10.5% cases, respectively. Compared with IDC, a significant association of MC was noted with age, Ki67 index, tumor (T)-stage, N-stage, and tumor grade. MC cases had a higher mean age than IDC cases. Comparative analysis revealed that MC had a lower frequency of axillary metastasis, a lower mean Ki67 index, and a lower tumor grade than IDC. About biomarker status, MC was noted to have a higher frequency of ER and PR expression, and a lower frequency of HER2/neu expression than IDC. Conclusion MC is a rare subtype of breast cancer. However, it is important to recognize this subtype of breast cancer as it is associated with a prognostically better pathological profile, such as lower tumor grade and Ki67 index, lower frequency of axillary metastasis, higher expression of ER and PR, and lower expression of HER2/neu.