Spindle Cell Carcinoma Research Articles

Cytological and Ultrastructural Findings of Mucinous Tubular and Spindle Cell Carcinoma: A Case Report

The 2016 World Health Organization Classification of Tumors recognized mucinous tubular and spindle cell carcinoma (MTSCC) as a rare histological variant of renal cell carcinoma (RCC). To date, a limited number of studies have reported this tumor concerning histology, and only a handful of those have reported cytological and ultrastructural features. This study aims to report a case of MTSCC in a female patient in her early 50s who presented with a chief complaint of gross hematuria, and to discuss relevant cytological and ultrastructural findings. Imaging revealed a 30 mm tumor in the left kidney, suggesting the presence of RCC, and left nephrectomy was performed. In addition, scratched cytology of tumor surface revealed clusters of tumor cells with clear cell boundaries extending two-dimensionally in papillary or dendritic arrangements with interspersed blood vessels and stromal components that were stained light green. Histologically, the tumor was composed of small and uniform cells arranged in elongated tubular architectures and spindle fascicles with occasional papillary structures; the stroma was acidophilic and contained colloidal substances that tested positive for Alcian blue and periodic acid-Schiff stain. Concordant with immunohistochemical results, the tumor was diagnosed with MTSCC. Furthermore, transmission electron microscopy revealed tubular structures with microvilli, abundance of mitochondria in the cytoplasm, cellular interdigitations and widened interstitium.

Low-Grade Fibromatosis-Like Spindle Cell Carcinoma of the Breast: a Mimicker of Benign Mesenchymal Tumors

We described a case of low-grade fibromatosis-like spindle cell carcinoma (FLSCC) of the breast of a 49-year-old woman, which was diagnosed by excisional biopsy. The histopathology was characterized by bland neoplastic spindle cells with mild or no nuclear atypia, mimicking a benign mesenchymal tumor. An immunopanel of markers including pancytokeratin, p63, smooth muscle actin (SMA), CD10, and β-catenin was performed to establish the diagnosis and exclude other mimickers. The patient subsequently received modified radical mastectomy and was alive without disease for 10-year follow-up. Low-grade fibromatosis-like spindle cell carcinoma is a rare subtype of metaplastic carcinomas of the breast and typically occurs as palpable breast mass in an older woman. It can be histologically confused with nodular fasciits, desmoids-type fibromatosis, and inflammatory myofibroblastic tumor. Immunohistochemical study was essential for a correct diagnosis. It behaves as a locally aggressive disease but with a low potential of regional lymph node or distant metastasis.

Infarct-Like Spindle Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 4 Cases.

Pulmonary spindle cell carcinoma is a rare and aggressive malignancy that often mimics benign conditions. We report 4 cases that simulate a pulmonary infarction, 2 of which were misdiagnosed. Patients were 3 men and 1 woman, smokers, presenting chest pain. All cases appeared as pleural-based, solitary, and rounded nodules. Patients underwent wedge resections followed by adjuvant chemotherapy (3/4) but died of disease. At histology, lesions consisted of widely necrotic nodules surrounded by organizing fibrosis and pleuritis. Examination and immunostains with pan-cytokeratins and epithelial membrane antigen (EMA) revealed atypical spindle cells encircling necrotic tissue and involving the vascular wall. Positive staining with PD-L1 was noted. Molecular analysis showed KRAS (2/4) and TP53 (1/4) mutations, whereas EGFR, ALK, and ROS1 alterations were not detected. Although in a limited series, these cases further evidence the treacherous appearance of spindle cell carcinomas and the need for careful attention when examining pulmonary infarcted tissue, thus requiring extensive sampling, meticulous examination of vascular structures, and immunostaining with cytokeratins.

A rare case of Mucinous, tubular and spindle cell carcinoma of kidney and Histomorphological study of renal cell tumours

A rare case of Mucinous, tubular and spindle cell carcinoma of kidney and Histomorphological study of renal cell tumours - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2020.033, Indian Journal of Pathology and Oncology-Indian J Pathol Oncol

Synchronous Mucinous Tubular and Spindle Cell Carcinoma of the Kidney and Papillary Carcinoma of the Thyroid

A 55 year old female, presented with flank pain and fullness since 2 years. On examination, a 10x10cm, ballotable lump was present in the right flank. CT Abdomen showed a 9.5x8.8 cm, exophytic mass lesion in the right kidney with patchy arterial enhancement and heterogenous enhancement in the venous phase. Whole body PET CT showed well defined, metabolically active masses in the right kidney, thyroid and cervical lymph nodes. Nephrectomy specimen received, showed a tumor measuring 12x7x6.5 cm creamy-white, fleshy, replacing the kidney. Histopathology revealed an unusual renal neoplasm with tubule formation merging with bland spindle cells and a focal myxoid stroma. Tumor cells were immunoreactive for CK7, EMA, vimentin and were negative for PAX8, CD10 & AMACR. The diagnosis of Mucinous Tubular and Spindle cell carcinoma (MTSCC) was established. FNAC of the thyroid nodules showed a classic papillary thyroid carcinoma.

Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers

IntroductionSpindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative (TNBC: estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype. It is associated with a marked resistance to conventional chemotherapy and has an overall poor outcome. Materials and MethodsTwenty-three pure spindle cell carcinomas of the breast (18 primary and 5 recurrent/metastatic) were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing. ResultsThe majority (21/23) of spindle cell carcinomas were TNBC. Estrogen and androgen receptor expression above the therapeutic thresholds were detected in 2 cases each. Pathogenic gene mutations were identified in 21 of 23 cases, including PIK3CA, TP53, HRAS, NF1, and PTEN. One case with matched pre- and post-chemotherapy samples exhibited a consistent mutational profile (PIK3CA and HRAS mutations) in both samples. Gene amplifications were present in 5 cases, including 1 case without detectable mutations. The spindle cell carcinomas cohort had consistently low total mutational burden (all below the 80th percentile for the entire TNBC cohort). All tumors were microsatellite stable. Programmed death-ligand 1 expression was observed on both tumor cells (in 7/21 cases), and in tumor-infiltrating immune cells (2/21 cases). ConclusionsSpindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but owing to the lack of uniform findings, individual patient profiling is necessary. Detection of individual combinations of biomarkers should improve treatment options for this rare but aggressive disease.

A Comparison of the Pathological Types of Undifferentiated Carcinoma of the Pancreas

This study aimed to identify the detailed clinicopathological features of undifferentiated carcinoma of the pancreas (UCP). We investigated clinical, imaging features and the prognoses of 261 patients; 8 were our patients, and the remainder were identified by searching English-language articles in PubMed. We classified patients with UCP into 3 types based on pathological findings: osteoclast-like giant cell-associated carcinoma, pleomorphic cell carcinoma (PLC), and spindle cell carcinoma. There were no remarkable differences in clinical, radiological features between these 3 types. However, PLCs were significantly more likely to be unresectable than were the other 2 types (P < 0.001). Patients with osteoclast-like giant cell-associated carcinoma achieved the best overall survival (OS) rates (P < 0.001), whereas those with spindle cell carcinoma had significantly longer OS rates than did those with PLC (P = 0.004). These OS patterns were maintained when considering only those patients who underwent resection. Patients with PLC had both lower curative resection and high lymph node metastasis rates (P = 0.029, P = 0.023). Patients who underwent resection had more favorable prognoses than did those who did not. Surgery is the first choice for resectable UCP. Pleomorphic cell carcinoma is particularly malignant; postoperative treatment should be introduced immediately.

Mucinous tubular and spindle cell carcinoma of kidney: A case report of a mucin and stroma poor tumour causing diagnostic difficulty

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and unusual variant of renal cell carcinoma (RCC). We report an unusual tumour in an 81-year-old male with an incidental finding of a tumour in the lower pole of the left kidney. The core biopsy showed a renal cell carcinoma with mostly tubular morphology and an immunophenotype indistinguishable from papillary renal cell carcinoma. The partial nephrectomy showed a tumour comprising predominantly tubular structures with focal abortive papillae, psammomatous calcifications and scattered small aggregates of foam cells. Only focal areas showed myxoid change and spindle cells, but this made the diagnosis of a mucinous tubular and spindle cell carcinoma more straightforward. This case highlights the importance of recognising a mucin/stroma poor variant of MTSCC of the kidney and how the entity can cause diagnostic confusion with papillary renal cell carcinoma as there is morphologic and immunophenotypic overlap, particularly on core biopsy.

Soft Tissue Special Issue: Cutaneous Pleomorphic Spindle Cell Tumors.

This manuscript provides an overview of pleomorphic spindle cell tumors presenting on sun-damaged skin of the elderly and includes discussions of atypical fibroxanthoma, pleomorphic dermal sarcoma, spindle cell and metaplastic squamous cell carcinoma, spindle cell and dedifferentiated melanoma and poorly differentiated cutaneous angiosarcoma. These tumors share many of the clinical presenting and histological features, making confident diagnosis challenging. A reliable and robust diagnosis is necessary to predict behavior as the biologic potential of these tumors ranges from benign (e.g. atypical fibroxanthoma) to outright malignant with poor survival rates (e.g. cutaneous angiosarcoma). The salient clinical, histologic and immunohistochemical characteristics are discussed in detail with emphasis on distinguishing features and differential diagnosis to provide the reader with a better understanding of these entities and helpful clues for a more robust diagnosis.

Avoidance and Period-Shortening of Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer in Stages I and II: Importance of Ki-67 Labeling Index and the Recognition of Apocrine-Type Lesions.

Background:Triple-negative breast cancer encompasses heterogeneous subtypes. Neoadjuvant chemotherapy is ineffective against some triple-negative breast cancers, while others show a favorable prognosis despite chemoresistance.Methods:A total of 51 cases with stages I and II triple-negative breast cancer were analyzed; 34 triple-negative breast cancers treated with neoadjuvant chemotherapy were divided into “good responders” (n = 22), showing therapeutic effect G2b or G3 in surgical specimens, and “poor responders” with therapeutic effect G0, G1a, G1b, and G2a (n = 12). Neoadjuvant chemotherapy was spared in 17 cases (non-neoadjuvant chemotherapy group). Apocrine-type triple-negative breast cancer was defined as triple-negative breast cancer immunoreactive for both androgen receptor and forkhead-box protein A1. Triple-negative breast cancer other than apocrine-type (n = 16) and special types (myoepithelial, medullary, adenoid cystic, and spindle cell carcinomas, n = 6) was categorized as basal-like subtype (n = 29). Prognosis was evaluated in each category.Results:Neoadjuvant chemotherapy provoked significant effects against basal-like triple-negative breast cancer with high Ki-67 labeling (≧50%), and tumor-infiltrating lymphocytes predicted high chemosensitivity. Neoadjuvant chemotherapy was avoidable in triple-negative breast cancer of apocrine- and special types showing low (<50%) Ki-67 labeling. Ten (59%) lesions in the non-neoadjuvant chemotherapy group belonged to the apocrine-type. When clinical complete remission shown by contrast-enhanced magnetic resonance imaging was reached in the course of neoadjuvant chemotherapy against basal-like triple-negative breast cancer, the neoadjuvant chemotherapy period was shortened in 14 (64%) of 22 good responders. Disease-free and overall survival rates were excellent in all groups.Conclusions:The following 2 hypothetical proposals should be proven by large-scale clinical trials. Immunohistochemical recognition of apocrine-type triple-negative breast cancer with low Ki-67 labeling is important for avoiding ineffective/unnecessary neoadjuvant chemotherapy. By employing appropriate clinical imaging, period-shortening is achievable in basal-like triple-negative breast cancer with high Ki-67 labeling.

Changes in the classification of malignant colon epithelial neoplasms. (WHO, 2019, 5th edition)

There are not many changes compared to 2010 in WHO classification (2019) of colon adenocarcinomas. Cribriform comedo-type adenocarcinoma (ICD-O code: 8201/3), spindle cell carcinoma (8032/3), squamous cell carcinoma (8070/3) are excluded; carcinoma with a sarcomatoid component (8033/3), poorly cohesive carcinoma (8490/3) and adenoma-like adenocarcinoma (8262/3) were added. The important histological characteristics in the conclusion should indicate the presence of lymphatic invasion, intra- and extramural vascular invasion, perineural invasion, grading, «tumor budding» and the immune microenvironment. In the 5th edition of the classification a large section has been added regarding molecular diagnostics and molecular prognostic factors of colorectal cancer. Correspondence was found between two different classifications based on two different approaches: genomic (according to DNA analysis) and transcriptomic (according to RNA analysis). According to the genomic classification two large groups of colorectal cancer are distinguished: hypermutated and non-hypermutated cancers that correspond to molecular pathways with the development of microsatellite and chromosomal instabilities, respectively. The section of neuroendocrine tumors did not undergo significant changes. It is not recommended to use the term «carcinoid» to refer to a neuroendocrine tumor G1, that is, the term «carcinoid» is excluded.

Histopathological Assessment for Esophageal Squamous Cell Carcinoma.

Histological assessment of esophageal squamous malignancies is crucial for management of patients with the cancer as well as working in research on the cancer. The squamous malignancies in the esophagus comprise squamous dysplasia and squamous cell carcinoma. Current classification of squamous dysplasia in the esophagus is to divide it into low grade and high grade. Most of the esophageal squamous cell carcinomas are of conventional type and divided into well, moderately, and poorly differentiated. The variants of esophageal squamous cell carcinoma include basaloid squamous carcinoma, spindle cell carcinoma, and verrucous carcinoma. Preoperative chemoradiation is used commonly in the treatment of esophageal squamous cell carcinoma and induces changes in morphology. Tumor regression grading systems based on the percentage of the remaining carcinoma cells are used to assess the response to the neoadjuvant therapy in the cancer. Additional histological parameters including lymphovascular invasion, perineural invasion, clearance of resection margins, and carcinoma in the nodal and distant metastatic sites provide essential information for the management of the patient with the cancer.

Bilateral renal mucinous tubular and spindle cell carcinoma (MTSCC) – an extremely rare occurrence in children

Bilateral renal mucinous tubular and spindle cell carcinoma (MTSCC) – an extremely rare occurrence in children

The promising role of mucin 4 in association with D2-40 immunohistochemistry in differentiating pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

Background Malignant mesothelioma is considered as a rare, aggressive malignant tumor that arises from mesothelial cells of the pleura. Pulmonary spindle cell carcinoma and pleomorphic carcinomas are considered as subtypes of sarcomatoid carcinoma, with an incidence of 2 and 3% of all lung malignancies. The differential diagnosis between sarcomatoid mesothelioma and lung sarcomatoid carcinoma by immunohistochemical markers has not been reached and requires further study. The aim of this study was to investigate the role of mucin 4 (MUC4) and D2-40 in differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma. Materials and methods The cases were divided into 20 cases of sarcomatoid mesothelioma and 14 cases of lung sarcomatoid carcinoma and were immunostained for MUC4 and D2-40 using streptavidin-biotin methods. Results MUC4 expression was seen in tumor cells of 11 (79%) lung sarcomatoid carcinoma cases. All cases of sarcomatoid mesothelioma showed negative immunostaining for MUC4 (0%). D2-40 immunostaining was positive in 16 (80%) cases of sarcomatoid mesothelioma. D2-40 expression was observed in two (14%) lung sarcomatoid carcinoma cases. The negative expression of MUC4 showed 78.57% sensitivity; however, specificity was 100%. The positive expression of D2-40 showed 80% sensitivity and 85.71% specificity. MUC4-negative expression and D2-40-positive expression were statistically significant. Conclusion We conclude that MUC4 and D2-40 immunohistochemical markers can differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma. The combination of the two markers increases sensitivity and specificity for both.

A Two-year Surviving Case of Primary Spindle Cell Carcinoma of the Lung after Adjuvant Chemotherapy

A Two-year Surviving Case of Primary Spindle Cell Carcinoma of the Lung after Adjuvant Chemotherapy

Spindle Cell Carcinoma of the Breast with Early Local Recurrence after Surgery

Spindle Cell Carcinoma of the Breast with Early Local Recurrence after Surgery

Clinical outcome and comparison between squamous and non-squamous cell carcinoma of the larynx

Background: The various pathological types of non-squamous cell carcinomas (nSCCs) of the larynx accounted for about 5% laryngeal malignancies, but the knowledge regarding these pathological behaviors, therapeutic models and prognostic factors was limited.Objectives: To investigate the clinical characteristics and the survival outcomes of nSCCs of the larynx.Material and methods: A total of 106 patients diagnosed with laryngeal nSCC between 2003 and 2014 were retrospectively investigated from a cohort of 4,796 patients with laryngeal malignancies.Results: Spindle cell carcinoma, malignant salivary gland carcinoma, neuroendocrine carcinoma, non-Hodgkin’s lymphomas, and carcinosarcoma accounted for the majority of the nSCCs of the larynx. In laryngeal nSCCs (excluding non-Hodgkin lymphomas), there was no significant difference in overall survival (OS) by tumor subsite (p = .818), clinical-stage (p = .051) or T stage (p = .412), but the difference in OS by N stage was statistically significant (p = .001). Upon comparison of propensity score-matched groups, the OS was longer in SCCs of the larynx (p = .0004).Conclusions and significance: Primary nSCC of the larynx is rare, and its diagnosis depends on comprehensive immunohistochemical examination, as the clinical characteristics are non-specific compared with SCC. The overall prognosis of nSCC is relatively poor compared with that of SCC in the larynx.

EXTENSIVE SPINDLE CELL CARCINOMA IN THE LIP—A CASE REPORT

Spindle cell carcinoma (SpCC) is considered a rare high malignant variant of squamous cell carcinoma (SCC) occurring predominantly in the upper aerodigestive tract. Lane tumor is a synonym for SpCC and is an uncommon poorly differentiated type of SCC comprising up to 3%. SpCC most commonly occurs in the sixth to seventh decades of life and usually affects men. A 66-year-old white patient was presenting an extensive ulcerated lesion affecting the lower lip with infiltrative fibroelastic consistency, local symptomatology, and 1 year of evolution. An incisional biopsy was performed, and the histopathologic findings were compatible with SpCC. Immunohistochemistry was also performed, which showed positivity for S-100. The association of clinical and histopathologic characteristics and the immunohistochemical analysis led to the diagnosis of SpCC. The patient was guided and referred to a head and neck surgeon for treatment.

Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma.

Pulmonary sarcomatoid carcinoma (PSC) is a heterogeneous category of primary lung cancer accounting from 0.3% to 3% of all primary lung malignancies. According to the most recent 2015 World Health Organization (WHO) classification, PSC includes several different variants of malignant epithelial tumors (carcinomas) histologically mimicking sarcomas showing or entirely lacking a conventional component of non-small cell lung cancer (NSCLC). Thus, this rare subheading of lung neoplasms includes pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, pulmonary blastoma, and carcinosarcoma. A diagnosis of PSC may be suspected on small biopsy or cytology, but commonly requires a surgical resection to reach a conclusive definition. The majority of patients with PSC consists of elderly, smoking men with a large, peripheral mass characterized by well-defined margins. However, presentation with a central, polypoid endobronchial lesion is well-documented, particularly in pleomorphic carcinoma and carcinosarcoma showing a squamous cell carcinoma component. As expected, PSC may pose diagnostic problems and immunohistochemistry is largely used when pathologists deal these tumors in routine practice. Indeed, PSC tends to overexpress molecules associated with the epithelial-to-mesenchymal transition, such as vimentin, but the panel of immunostains also includes epithelial markers (cytokeratins, EMA), TTF-1, p40 and negative markers (e.g., melanocytic, mesothelial and sarcoma-related primary antibodies). Although rare, PSC has increased their interest among oncologist community for different reasons: a. identification of the epithelial-to-mesenchymal phenomenon as a major mechanism of secondary resistance to tyrosine kinase inhibitors; b. over-expression of PD-L1 and effective treatment with immunotherapy; c. identification of c-MET exon 14 skipping mutation representing an effective target to crizotinib and other specific inhibitors. In this review, the feasibility of the diagnosis of PSC, its differential diagnosis and novel molecular findings characterizing this group of lung tumor are discussed.

S100a4 upregulation in Pik3caH1047R;Trp53R270H;MMTV-Cre-driven mammary tumors promotes metastasis

BackgroundPIK3CA mutations are frequent in human breast cancer. Pik3caH1047R mutant expression in mouse mammary gland promotes tumorigenesis. TP53 mutations co-occur with PIK3CA mutations in human breast cancers. We previously generated a conditionally activatable Pik3caH1047R;MMTV-Cre mouse model and found a few malignant sarcomatoid (spindle cell) carcinomas that had acquired spontaneous dominant-negative Trp53 mutations.MethodsA Pik3caH1047R;Trp53R270H;MMTV-Cre double mutant mouse breast cancer model was generated. Tumors were characterized by histology, marker analysis, transcriptional profiling, single-cell RNA-seq, and bioinformatics. Cell lines were developed from mutant tumors and used to identify and confirm genes involved in metastasis.ResultsWe found Pik3caH1047R and Trp53R270H cooperate in driving oncogenesis in mammary glands leading to a shorter latency than either alone. Double mutant mice develop multiple histologically distinct mammary tumors, including adenocarcinoma and sarcomatoid (spindle cell) carcinoma. We found some tumors to be invasive and a few metastasized to the lung and/or the lymph node. Single-cell RNA-seq analysis of the tumors identified epithelial, stromal, myeloid, and T cell groups. Expression analysis of the metastatic tumors identified S100a4 as a top candidate gene associated with metastasis. Metastatic tumors contained a much higher percentage of epithelial–mesenchymal transition (EMT)-signature positive and S100a4-expressing cells. CRISPR/CAS9-mediated knockout of S100a4 in a metastatic tumor-derived cell line disrupted its metastatic potential indicating a role for S100a4 in metastasis.ConclusionsPik3caH1047R;Trp53R270H;MMTV-Cre mouse provides a preclinical model to mimic a subtype of human breast cancers that carry both PIK3CA and TP53 mutations. It also allows for understanding the cooperation between the two mutant genes in tumorigenesis. Our model also provides a system to study metastasis and develop therapeutic strategies for PIK3CA/TP53 double-positive cancers. S100a4 found involved in metastasis in this model can be a potential diagnostic and therapeutic target.