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.

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 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.