Pleomorphic Carcinoma Research Articles

Development and Evaluation of a Convolutional Neural Network for Microscopic Diagnosis Between Pleomorphic Adenoma and Carcinoma Ex-Pleomorphic Adenoma.

To develop a model capable of distinguishing carcinoma ex-pleomorphic adenoma from pleomorphic adenoma using a convolutional neural network architecture. A cohort of 83 Brazilian patients, divided into carcinoma ex-pleomorphic adenoma (n = 42) and pleomorphic adenoma (n = 41), was used for training a convolutional neural network. The whole-slide images were annotated and fragmented into 743 869 (carcinoma ex-pleomorphic adenomas) and 211 714 (pleomorphic adenomas) patches, measuring 224 × 224 pixels. Training (80%), validation (10%), and test (10%) subsets were established. The Residual Neural Network (ResNet)-50 was chosen for its recognition and classification capabilities. The training and validation graphs, and parameters derived from the confusion matrix, were evaluated. The loss curve recorded 0.63, and the accuracy reached 0.93. Evaluated parameters included specificity (0.88), sensitivity (0.94), precision (0.96), F1 score (0.95), and area under the curve (0.97). The study underscores the potential of ResNet-50 in the microscopic diagnosis of carcinoma ex-pleomorphic adenoma. The developed model demonstrated strong learning potential, but exhibited partial limitations in generalization, as indicated by the validation curve. In summary, the study established a promising baseline despite limitations in model generalization. This indicates the need to refine methodologies, investigate new models, incorporate larger datasets, and encourage inter-institutional collaboration for comprehensive studies in salivary gland tumors.

The utility of PET-CT in baseline and sequential characterisation of Pulmonary Pleomorphic Carcinoma

Pulmonary Pleomorphic Carcinomas (PPCs) represent a rare and aggressive subtype of Non-Small Cell Lung Cancer (NSCLC) that can only be definitively diagnosed on a surgical specimen. This study utilised PET-CT to evaluate radiological characteristics of PPCs. This study retrospectively evaluated the radiological characteristics of PCCs diagnosed in St James’s Hospital Dublin between 2012-2023. Computed Tomography (CT) and Positron Emission Tomography (FDG-PET) imaging features (size, location, density, shape, invasion, and growth kinetics) and standard uptake value for each lesion were evaluated. 39 PCCs were identified with a mean age of 66.5 years (range: 49-82 years). FDG-PET was performed in all 39 cases. Tumours demonstrated a high FDG uptake at baseline with a mean (SUV) of 12.6 (range: 1.4 - 36.9). A second interval PET-CT on average 3.3 months after the first in 3 cases demonstrated over 120% increase in SUV. The mean tumour size was 4.3 cm (range: 1.0 - 14.5 cm). Tumours developed rapid interval growth, reaching a mean maximum diameter of 6.6 cm (53.4%) within a mean of 2.1 months. Tumours were predominantly located in the upper lobe (71.8 %) and displayed necrotic features in 53.8 % of cases. 82.1% of tumours invaded the mediastinum. This study describes the largest cohort of Pulmonary Pleomorphic Carcinoma in the literature. Tumours demonstrate a high SUV on baseline imaging and demonstrate rapid growth on interval imaging and central necrosis. Please click on the 'PDF' for the full abstract!

Pleomorphic Lobular Carcinoma In Situ Composed of Signet-Ring Cells Mimicking Ductal Carcinoma In Situ with A Papillary Pattern: A Case Report.

While some forms of invasive or in situ carcinoma of the breast may be partly composed of signet-ring cells, signet-ring cells rarely become a prominent feature of pleomorphic lobular carcinoma in situ (LCIS). We report a rare example of pleomorphic LCIS composed predominantly of signet-ring cells with a papillary pattern mimicking ductal carcinoma in situ (DCIS). A 58-year-old woman presented with a mass in the left breast detected by ultrasonography. Fourteen years previously, the patient underwent right breast-conserving surgery for invasive breast carcinoma of no special type. Ultrasonography revealed an irregular parallel, angular hypoechoic mass measuring 1.5 cm in the left breast. An ultrasound-guided core needle core biopsy was conducted. Microscopically, the lesion was composed of epithelial cells supported by a fibrovascular stroma. The majority (> 70%) of the lesional cells between the fibrovascular stalks showed signet-ring cell features. Some of the nuclei of the signet-ring cells showed intermediate-grade atypia. A mucicarmine stain showed intracytoplasmic mucin in the signet-ring cells. Immunohistochemistry for E-cadherin was negative in the tumor cells. After surgical excision, the final diagnosis was a pleomorphic LCIS. To our knowledge, there have been no previous reports of pleomorphic LCIS consisting primarily of signet-ring cells with a papillary pattern.

A case of postoperative relapse of pulmonary pleomorphic carcinoma successfully treated with Pembrolizumab

A case of postoperative relapse of pulmonary pleomorphic carcinoma successfully treated with Pembrolizumab

Automated feathered edge blood smear analysis: early diagnosis of carcinocythemia in a case of disseminated intravascular coagulation with multi-organ failure.

Carcinocythemia, known as the presence of circulating tumor cells in the peripheral blood, is difficult to detect when the carcinoma cells are minimally present. We describe a case of a 56-year-old patient presenting with disseminatedintravascular coagulation (DIC) and multiple organ failure. Despite initial suspicion of sepsis, a peripheral blood smear showed the presence of atypical cells, mainly located at the feathered edge, leading to a presumptive diagnosis of carcinocythemia of unknown primary origin. The presence of a high-fluorescent cell population detected by our hematology analyzer (Sysmex XN-9100) and immunohistochemical staining with pancytokeratin AE1/AE3 confirmed the carcinoma cell origin. The patient died 4 days after referral to our hospital. Postmortem examination revealed a pleomorphic lobular breast carcinoma (triple-negative, androgen receptor-negative). Given the clinical acuity of patients with carcinocythemia, early diagnosis is essential to guide management. This case underscores the importance of optimizing current workflows relying on complex flagging algorithms and enhanced digital imaging to aid in the early detection of such rare condition. When patients present with DIC of unknown origin and high fluorescent signals are detected on the hematology analyzer, carcinocythemia should actively be ruled out by extensive microscopic peripheral blood examination.

Mesothelioma: molecular pathology and biomarkers.

Diffuse mesotheliomas are characterized by recurrent genomic alterations involving tumor suppressors and epigenetic regulators such as BAP1, CDKN2A, MTAP, and NF2. Depending on the differential diagnosis as informed by histologic assessment, one can apply the appropriate immunohistochemical and/or molecular panels to reach the correct pathologic diagnosis, sometimes even in cases with limited tissues. Biomarkers aid in the diagnosis of mesothelioma in the following scenarios: 1)For atumor that is overtly malignant, how can one distinguish mesothelioma from other tumors? 2)For amesothelial proliferation, how can one distinguish mesothelioma from areactive process? To distinguish mesotheliomas from carcinomas, at least two positive and two negative markers are currently recommended. To distinguish sarcomatoid mesothelioma from pleomorphic carcinoma, even more markers-and sometimes molecular testing-are needed. To distinguish mesothelioma from reactive mesothelial conditions, useful immunohistochemical biomarkers include BAP1, MTAP, and merlin, which serve as surrogates for the corresponding gene mutation status. In patients with unusual clinical history, for tumors with apeculiar microscopic appearance, and/or in cases with an equivocal immunophenotypic profile, molecular testing can help to exclude mimics and to confirm the pathologic diagnosis.

A histomorphological and immunohistochemical analysis of invasive lobular carcinoma of breast: A case series

Invasive lobular carcinoma (ILC) is the second most common special subtype of invasive breast carcinoma comprising 5–15%. ILC defines as invasive carcinoma comprising non-cohesive single-file linear pattern in fibrous stroma. The aim of the study was to evaluate the histomorphological features and immunohistochemical analysis of ILC. A total of 19 cases were encountered from March 2020 to February 2024 out of 129 breast cancers. The sociodemographic profiles and clinicopathological parameters of the patients were studied with special emphasis on their morphology and hormone receptor status. The mean age of patients is 42.8 years. Out of 19 cases, 84.2% showed feature of classic type, 5.2% of tubule-lobular, and 10.5% of pleomorphic lobular carcinoma. The majority of cases (63.2%) showed histologic Grade 2, and 10.5% showed Grade 3. On immunohistochemistry examination, 79% were estrogen receptor (ER) and progesterone receptor (PR) positive with 10.5% of cases was human epidermal growth factor receptor 2/neu (HER2/neu) positive. Our study showed higher cases of classic type ILC, mostly of histologic Grade 2; higher ER-PR receptor positivity and HER2/neu negativity.

The histopathological spectrum and molecular changes associated with KRAS G12C mutation in non-small cell lung carcinoma

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant. KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.

Tracing Tumor Heterogeneity of Pleomorphic Carcinoma of the Lung

IntroductionPulmonary pleomorphic carcinoma (PPC) is an aggressive and highly heterogeneous NSCLC whose underlying biology is still poorly understood. MethodsA total of 42 tumor areas from 20 patients with PPC were microdissected, including 39 primary tumors and three metastases, and the histologically distinct components were subjected to whole exome sequencing separately. We further performed in silico analysis of microdissected bulk RNA sequencing and methylation data of 28 samples from 14 patients with PPC. We validated our findings using immunohistochemistry. ResultsThe epithelial and the sarcomatoid components of PPCs shared a large number of genomic alterations. Most mutations in cancer driver genes were clonal and truncal between the two components of PPCs suggesting a common ancestor. The high number of alterations in the RTK-RAS pathway suggests that it plays an important role in the evolution of PPC. The metastases morphologically and genetically resembled the epithelial or the sarcomatoid components of the tumor.The transcriptomic and epigenetic profiles of the sarcomatoid components of PPCs with matched squamous-like or adenocarcinoma-like components differed from each other, and they shared more similarities to their matched epithelial components. NCAM1/CD56 was preferentially expressed in the sarcomatoid component of squamous-like PPCs, whereas CDH1/E-Cadherin expression was down-regulated in the sarcomatoid component of most PPCs. ConclusionLung adenocarcinoma-like PPCs are mainly driven by RTK-RAS signaling, whereas epithelial-mesenchymal transition programs as highlighted by increased NCAM1 and decreased CDH1 expression govern the epithelial-sarcomatoid transition between the clonally related tumor components. Several alterations in PPCs pinpoint therapeutic opportunities.

Pulmonary blastoma: A rare, unexpected diagnosis mimicking hydatid cyst on radiology

Pulmonary blastomas (PB) are rare, aggressive tumours which constitute <0.1% of resected lung cancers. The fifth edition of WHO classification of thoracic tumors categorises them under sarcomatoid carcinomas along with pleomorphic carcinoma and carcinosarcoma. PBs are large and aggressive tumors that portend a poor prognosis with limited response to standard chemotherapy and chiefly occur in the fourth to fifth decade of life. Here, we present a unique case of a PB with extensive cystic degeneration in a young female, mimicking a hydatid cyst.

A Single-center Surgical Case Series of Pulmonary Pleomorphic Carcinoma

A Single-center Surgical Case Series of Pulmonary Pleomorphic Carcinoma

Characteristics of Triple Negative Subtype Breast Cancer in Dr. Hasan Sadikin General Hospital for 5 Years (2019-2023): An Observational Study

Background: Triple-negative breast cancer has a percentage of 15% to 20% in breast cancer patients at the time of first diagnosis. Guidelines from St. Gallen guidelines, the American Society of Clinical Oncology, and the American College of Pathology state that triple-negative breast cancer is breast cancer with ER and PR expression <1%. As an aggressive subtype, outcomes are poor when compared with hormone receptor-positive. Methods: This research is an observational study. The research subjects in this study were triple-negative breast cancer patients in Dr. Hasan Sadikin General Hospital, Surgical Oncology division, West Java, Indonesia, from October 2018 - November 2023. There were 702 research subjects who would be studied. Characteristics of triple-negative breast cancer were taken from medical records. Results: The results showed that the average age of the subjects was 47 years. Based on histology, the most common was Invasive Carcinoma of no special type (86.75%), followed by Invasive lobular carcinoma (7.26%), medullary carcinoma (1.7%), micropapillary carcinoma (0.99%), metaplastic carcinoma (2.36%) and the least amount is Pleomorphic invasive lobular carcinoma (0.71%). The side of the breast affected is not significant, and the highest grade is 3. The involvement of lymph node metastases is due to aggressive tumor subtypes and lymphovascular invasion. Lymphovascular invasion is known to be a negative prognostic factor. It is a late stage for metastasis and local recurrence. Conclusion: Triple-negative breast cancer is breast cancer that has histopathological heterogeneity; most of the tumors are grade 3 and have significant metastases in regional lymph nodes. There is no significant relationship between grading and regional lymph node metastases. there is a significant relationship between lymphovascular invasion and regional lymph nodes metastases.

Effect of histological subtype on the efficacy of perioperative chemotherapy in pulmonary sarcomatoid carcinoma: a retrospective study based on SEER population.

The efficacy of perioperative chemotherapy (PC) in pulmonary sarcomatoid carcinoma (PSC) is controversial. We conducted this study to investigate the effect of different histological subtypes on the efficacy of PC in PSC patients. Clinicopathological data of 811 PSC patients of different histological subtypes were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and log-rank test were used to evaluate the effects of PC on the overall survival (OS) and cancer-specific survival (CSS) in different subtypes of PSC patients. Propensity score matching (PSM) was used to reduce potential confounding effects. Subgroup analyses were conducted to further investigate the efficacy of PC in patients with different characteristics. A total of 210 (25.89%) enrolled PSC patients received PC. PC was not associated with OS or CSS benefit in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients, neither before nor after matching. But survival benefit of PC was observed in carcinosarcoma patients both before (5-year OS: 48.79% vs. 38.75%, P=0.01) and after (5-year OS: 51.29% vs. 17.54%, P=0.003) matching. Subgroup analyses showed that in patients whose tumor larger than 4 cm, PC was still associated with improved survival in carcinosarcoma, but not in the other histological subtypes of PSC. The efficacy of PC varies between different subtypes of PSC. Survival benefit of PC was only observed in carcinosarcoma patients, but not in pleomorphic carcinoma, giant cell carcinoma, or spindle cell carcinoma patients. Histological subtype should be considered when treating PSC patients with PC.

Comparison of Clinicopathological Features of Pleomorphic and Invasive Lobular Breast Carcinomas.

Accounting for about 15% of invasive lobular carcinomas and 1% of breast carcinomas, pleomorphic lobular carcinoma is known to be a rare histological subtype of invasive lobular carcinoma. Yet, it is more aggressive and produces a worse prognosis than other breast cancers. Ultimately, the present study compares the clinicopathological features of pleomorphic and invasive lobular breast carcinomas. In the study, we retrospectively evaluated the data of 262 patients with histological subtypes of classical and pleomorphic lobular cancers having been recruited for surgical operations. After resorting to Kolmogorov-Smirnov and Shapiro-Wilk tests to check the normality of distribution, the categorical and continuous variables were compared between the groups using the chi-square test and independent samples t test, respectively. In all analyses, we considered a P-value of <.05 to be statistically significant. Our findings revealed that the groups with lobular and pleomorphic groups significantly differed by Ki-67 value, estrogen receptor negativity, grade, multicentricity, multifocality, surgical margin positivity, completion mastectomy, and metachronous contralateral tumor (P < .05). We discovered that pleomorphic type was associated with higher grades, estrogen receptor negativity, and Ki-67 expression. The incidence of metachronous breast cancer was high in the pleomorphic group, which may be a noteworthy finding to be considered in follow-ups. In addition, the high rates of multicentricity and multifocality of tumors in the pleomorphic group may be associated with increased surgical margin positivity and a higher likelihood of mastectomy. In a nutshell, our findings may guide patients and surgeons regarding the type of intervention and reconstruction options to be adopted in prospective surgeries.

Pleomorphic Carcinoma of Pulmonary Location: Case Report and Review of the Literature

Pulmonary pleomorphic carcinoma is a rare primary lung tumor, part of the group of non-small cell cancers. We report the case of a 54-year-old patient, a chronic smoker who presented with hemoptysis evolving in a context of deterioration in general condition. Chest imaging revealeda left upper lobar tissue density mass with some hypodensity. The diagnosis of pleomorphic lung carcinoma was made based on histological data from bronchial biopsies, and classified as stage IVb according to the TNM classification (8th edition). Palliative chemotherapy was then offered to the patient. The evolution was marked by the death of the patient 2 months after diagnosis. Through this observation, we wish to shed light on this rare and particular histological type but just as aggressive as other pulmonary neoplasias.

MicroRNA copy number alterations in the malignant transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

This study used array comparative genomic hybridization to assess copy number alterations (CNAs) involving miRNA genes in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA), residual PA, and carcinoma ex pleomorphic adenoma (CXPA). We analyzed 13 PA, 4 RPA, 29 CXPA, and 14 residual PA using Nexus Copy Number Discovery software. The miRNAs genes affected by CNAs were evaluated based on their expression patterns and subjected to pathway enrichment analysis. Across the groups, we found 216 CNAs affecting 2261 miRNA genes, with 117 in PA, 59 in RPA, 846 in residual PA, and 2555 in CXPA. The chromosome 8 showed higher involvement in altered miRNAs in PAs and CXPA patients. Six miRNA genes were shared among all groups. Additionally, miR-21, miR-455-3p, miR-140, miR-320a, miR-383, miR-598, and miR-486 were prominent CNAs found and is implicated in carcinogenesis of several malignant tumors. These miRNAs regulate critical signaling pathways such as aerobic glycolysis, fatty acid biosynthesis, and cancer-related pathways. This study was the first to explore CNAs in miRNA-encoding genes in the PA-CXPA sequence. The findings suggest the involvement of numerous miRNA genes in CXPA development and progression by regulating oncogenic signaling pathways.

160 (PB-067) Poster - Risk of upstaging after a core biopsy diagnosis of classic, pleomorphic and non-classic lobular carcinoma in situ, a nationwide study

160 (PB-067) Poster - Risk of upstaging after a core biopsy diagnosis of classic, pleomorphic and non-classic lobular carcinoma in situ, a nationwide study

Metastatic Pleomorphic Lobular Carcinoma of the Breast to the Urinary Bladder: A Report of 10 Cases and Assessment of TRPS1 in the Differential Diagnosis With Plasmacytoid Urothelial Carcinoma.

Metastatic pleomorphic lobular carcinoma (MPLC) to the bladder is rare and has considerable histologic and immunohistochemical overlap with plasmacytoid urothelial carcinoma (PUC). To distinguish MPLC from PUC morphologically and immunohistochemically, including a newer marker, TRPS1. Ten MPLCs to the bladder were reassessed and stained with estrogen, progesterone, and androgen receptors; GATA3; keratin 5/6; HMWK; GCDFP-15; and TRPS1. Sixteen PUCs constituted controls. We studied 4 transurethral resections of bladder tumors and 6 biopsies from 10 women (median age, 69 years) who had breast cancer on average 15 years prior. Microscopic patterns included single cells and cords of cells (n = 4), nests/sheets of dyscohesive cells (n = 2), or both (n = 4). All tumors had cells with voluminous eosinophilic cytoplasm and eccentric nuclei mimicking PUC, and 7 of 10 tumors had signet ring cells. MPLCs were positive for estrogen (8 of 10), progesterone (3 of 7), and androgen receptors (4 of 10); GCDFP-15 (7 of 10); GATA3 (9 of 10); HMWK (7 of 8); and TRPS1 (7 of 10). No MPLCs stained for keratin 5/6 (n = 9). Of 16 PUCs, 2 showed faint and 2 demonstrated strong TRSP1 staining; 7 of 16 were negative for p63. MPLC to bladder often presents in patients with a remote history of breast cancer, exhibiting significant histologic and immunohistochemical overlap with PUC. Based on prior works and the current study, estrogen receptor (particularly SP-1), mammaglobin, and p63 help differentiate MPLC from PUC. Keratin 5/6 may aid in distinguishing a less frequent basal type PUC because it is typically negative in MPLC. Some PUCs express TRPS1. Caution should be exercised because immunophenotypes of these tumors greatly overlap, and ramifications of misclassification are major.

Motley and Immured-Lobular Carcinoma In situ Pleomorphic

Pleomorphic lobular carcinoma in situ represents as an exceptionally discerned, morphological subtype of lobular carcinoma in situ (LCIS). Neoplasm is contemplated to express a genetic and biological advancement of classic lobular carcinoma in situ and emerges as a direct precursor to invasive carcinoma breast. Initially scripted by Frost et al in 1996, pleomorphic lobular carcinoma in situ is contemplated as a morphologic variant of classic lobular carcinoma in situ.

Metastatic Pleomorphic Carcinoma of the Lung with Extensive Chromosomal Rearrangements: An Autopsy Case with a Literature Review.

We herein report a 47-year-old man who presented with progressive paraparesis. Imaging revealed a right upper pulmonary nodule, massive bilateral adrenal metastases, thoracolumbar vertebral osteolysis, and subcutaneous nodules. A biopsy of the right buttock nodule revealed a poorly differentiated metastatic carcinoma with high programmed cell death-ligand 1 expression and extensive chromosomal rearrangements. The patient died 10 days after the initiation of pembrolizumab treatment. Autopsy findings confirmed pulmonary pleomorphic carcinoma with extensive metastases. Quantification of chromosomal rearrangements revealed a jump-up mutation from the normal karyotype, followed by a further incremental increase in the degree of deviation.