Spindle Cell Carcinoma Research Articles

Primary Pulmonary Carcinomas with Spindle and/or Giant Cell Features: A Review with Emphasis in Classification and Pitfalls in Diagnosis.

Primary carcinomas of the lung are vastly represented by the conventional types of adenocarcinomas or squamous cell carcinomas. However, there are other types of non-small cell carcinomas that although uncommon represent a meaningful group that often pose a problem not only in diagnosis but also in classification. Spindle cell and/or giant cell carcinomas, although uncommon represent an important group of primary lung carcinomas. Important to highlight is that current criteria are rather ambiguous and likely not up to date, which renders the classification of these tumors somewhat more obscure. In addition, with the daily use of immunohistochemical stains, the classification of these tumors may also pose a different problem in the proper allocation of these tumors. Proper classification is highly important in the selection process that takes place using such material for molecular analysis. The current molecular characteristics of these tumors are limited and lack more in-depth studies and analyses that can provide specific targets for the treatment of patients with these tumors. The current review attempts to highlight the shortcomings in the current classification and definitions of these neoplasms as well as the more current view regarding these tumors when the use of immunohistochemical stains is employed.

Mucin-poor mucinous tubular and spindle cell kidney cancer and clear cell renal cell carcinoma: a rare clinical case

Mucinous tubular and spindle cell carcinoma of the kidney is a rare low-grade malignant tumour and accounts for less than 1% of all renal neoplasms. The classic morphological structure of the tumor is represented by three elements: spindle cells, ducts and myxoid or mucinous stroma. This tumor is indolent with a low risk of metastasis and a favorable outcome. However, cases with relapses, metastases to regional lymph nodes, and distant metastases, which were mainly characterised by high nuclear atypia, sarcomatoid transformation and other atypical morphological features are described in the literature. Several cases of mucin-poor and mucin-free mucinous tubular and spindle cell renal cell carcinoma have also been presented, making it difficult to differentiate from other renal cell carcinomas. There are reports of cases of mucin poor mucinous tubular and spindle cell carcinoma, which were accompanied by relapses and metastases. Thus, although the tumour is indolent, careful follow-up is necessary even after radical excision. In this article, we report a rare clinical case of combination of mucin-poor mucinous tubular and spindle cell carcinoma and clear cell renal cell carcinoma of the kidney in a 50-year-old man. The results of clinical and instrumental studies, as well as the morphological features of both tumors are presented. Due to the atypical morphological structure of mucinous tubular and spindle cell carcinoma, the final diagnosis was possible using an immunohistochemical method, which demonstrated the immunohistochemical profile characteristic of this tumour.

The many faces of Atypical fibroxanthoma.

Atypical fibroxanthoma (AFX) is an uncommon, primary dermal neoplasm of uncertain histogenesis, typically originating in the sun-damage skin of the head and neck of the elderly. Since first description in 1958, ∼3000 cases have been reported in the literature. However, the disease is underreported as the neoplasm is considered a standard diagnosis in the last decades. On the other hand, many earlier reports likely have included non-AFX mimics or aggressive pleomorphic dermal sarcomas. In contrast to its alarming high-grade histology, AFX behaves indolently with rare recurrences/ metastatic rate of <2%. The overall 10- and 20-year disease-specific survival rates are ∼ 100% and 98%, respectively. Histologically, AFX displays undifferentiated pleomorphic spindle cell morphology akin to undifferentiated pleomorphic sarcoma (UPS), a feature that was the basis of the abandoned historical terminology "MFH of skin". However, in contrast to other undifferentiated sarcomatoid neoplasms, AFX is notorious for its highly variable histology with a plethora of patterns, underlining a wide differential diagnosis. Notably, spindle cell, keloid-like, pleomorphic, epithelioid, rhabdoid, clear cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, osteoclast-rich, and many others have been recognized with varying frequencies. Immunohistochemically, AFX is characterized by nonspecific profile with block-type expression of CD10 and aberrant p53 pattern and lack of pankeratin and other lineage-specific epithelial, mesenchymal, melanocytic and hematolymphoid markers. Sarcomatoid melanoma, spindle cell carcinoma and cutaneous anaplastic large cell lymphoma are major considerations. Distinction of AFX from pleomorphic dermal sarcoma (PDS) is arbitrary and is based on presence of ≥ 1 of four unfavorable histological features: more than minimal subcutaneous involvement, coagulative necrosis, lymphovascular invasion and perineurial invasion.

Epidemiological Trends of Lung Tumours on Endobronchial Biopsy in Patients Presenting to Tertiary Care Hospital

Objective: To determine the epidemiological trends of lung tumours on endobronchial biopsy in patients presenting to our hospital.&#x0D; Study Design: Prospective longitudinal study.&#x0D; Place and Duration of Study: Department of Pulmonology, Pak Emirates Military Hospital, Rawalpindi Pakistan, from Nov 2021 to Jun 2022.&#x0D; Methodology: Two hundred eighty-seven patients who exhibited clinical and/or radiological signs of a lung mass were enrolled in this study. Bronchoscopy was done to identify endobronchial lesions, followed by endobronchial biopsies submitted for histopathology and immunohistochemistry to diagnose the exact type of tumour. Patients who underwent bronchoscopy for some other indication but were found to have an endobronchial mass incidentally were also included in the study.&#x0D; Results: Squamous cell carcinoma was the most common 107(37.3%), followed by small cell carcinoma 76(26.5%). Adenocarcinoma was diagnosed in 75 patients (26.1%). Diagnosis of carcinoid tumour was made in 6 patients (2.09%). There were 5 cases (1.7%) of poorly differentiated carcinoma and metastatic adenocarcinoma each. Large cell carcinoma was present only in 2 cases (0.7%). Strangely, two patients (0.7%) had small and Squamous cells simultaneously, and one had adenosquamous carcinoma. Other tumours, including mantle cell lymphoma, Rhabdomyosarcoma, mucoepidermoid carcinoma, neuroendocrine tumours, spindle cell carcinoma and sarcomatoid carcinoma, were found in 8 cases (2.8%).&#x0D; Conclusion: Squamous cell carcinoma is the most common centrally arising tumour in our population in both genders, followed by small cell carcinoma and adenocarcinoma.Keywords: Epidemiology, Endobronchial mass, Lung cancer, Squamous cell carcinoma.

The conundrum of metaplastic breast cancer: a single Egyptian institution retrospective 10-year experience (2011–2020)

BackgroundMetaplastic breast cancer (MetBC) still represents a conundrum owing to its peculiar histogenesis and molecular drivers that render it extremely resistant to standard chemotherapy with ultimate dismal survival.AimDescribe the Egyptian National Cancer Institute’s (NCI-E) experience with MetBC regarding its clinicopathologic features, treatment, and survival outcomes.Patients and methodsBetween 2011 and 2020, all MetBC patients presented to NCI-E were retrospectively evaluated. Original clinicopathologic data, therapeutic modalities, pathologic response to neoadjuvant chemotherapy (NACT), recurrence, and date of last follow-up/death were obtained from archived charts.ResultsA cohort of 135 females, the median age was 52 years, and median follow-up period was 40 months (range: 2.6–130.8). Two-thirds were triple negative (TN). Squamous carcinoma was prevalent in 74.8% followed by carcinoma with osseous/chondroid differentiation, spindle cell, and low-grade adenosquamous carcinoma encountered in 13.3, 7.4, and 4.5%, respectively. Modified radical mastectomy was done in 59.3%, and positive nodes (pN+) were depicted in 37.7%. Median Ki-67 was 45% (range: 10–88); grade III and lymphovascular invasion (LVI) were observed in 83.7 and 43.7%, respectively. Stage II was the most common (49%), whereas initial stage IV was encountered in 8.1%. Anthracyclines/taxane combinations were rampant in adjuvant/neoadjuvant settings. The latter was employed in 41 patients, with only 3 cases (7.3%) achieving pathologic complete response (pCR), while moderate/significant residual tumor burden was found in 83%. The 5-year DFS and OS were 56.4 and 57.6%, respectively. Spindle cell carcinoma showed the worst survival parameters in univariate analysis. On the multivariate level, higher tumor stage (pT3 & 4), Ki-67 ≥ 45%, and TN subtype were independent variables for worse DFS and OS; age ≥ 52 years and the presence of LVI were independent features for worse DFS, whereas pN+ was an independent parameter for worse OS.ConclusionsThis study further solidifies the dreadful response of MetBC to conventional chemotherapy regimens employed in common non-metaplastic pathologies. A radical shift in treatment standards tailored to combat the molecular landscape of this distinctive tumor is urgently needed. Immunotherapy and molecularly targeted agents demonstrated promising results in phase I and II trials with hopeful sooner implementation in phase III studies.

Epidemiologic and socioeconomic characteristics of Hispanics diagnosed with metastatic renal cell carcinoma in the US.

e16555 Background: Annually, there are over 400,000 new renal cell carcinoma (RCC) cases and more than 170,000 deaths worldwide. In the US, 80,000 new cases of RCC are diagnosed each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. RCC seems to have a greater incidence among Hispanics, with a nearly three-fold increase. The epidemiology of RCC in the Caucasian population has been previously studied. However, there is a knowledge gap on disparities in RCC on minority populations. Studying the epidemiology of RCC in Hispanics is integral to our community, where Hispanics make up 70%. Methods: We conducted a retrospective cohort study using the Florida Statewide Cancer Registry to describe the characteristics and rates of metastatic RCC (mRCC) among patients in the State between 1981 and April 2019. We identified ethnicity as Hispanic/Latino (HL) or non-Hispanic/Latino (NHL). Clinical presentation was categorized as mRCC at diagnosis/de novo based on SEER and TNM classification. Results: We analyzed 81,178 patients age 18 and older with an ICD-10 code C649 diagnosis of malignant neoplasm of an unspecified kidney. 69,359 patients (85%) were diagnosed with RCC based on ICD-O classification, and 10,959 (13%) had metastatic disease at the time of diagnosis. Of these patients with metastatic disease, 9,691 (87.12%) were identified as NHL and 1,170 (12.30%) as HL. At the time of diagnosis, more HLs were enrolled in Medicaid (11.99% vs. 4.03%) and were uninsured (9.36% vs. 4.28%) compared to NHLs. Amongst HLs with the country of birth data, 650 (87%) were foreign-born and 97 (13%) were US-born. The largest group of foreign-born HLs was from Cuba, with 337 patients (45.18%). While for both groups the highest number of patients were diagnosed in the seventh decade of life (USA 29.66% vs. foreign 27.23%), USA-born HLs were diagnosed more over the preceding two decades (age 39-58) than foreign-born HLs (45.82% vs. 33.51%). Conversely, foreign-born HLs were diagnosed later than US-born HLs (35.29% vs. 18.34%). Both groups kept the same top two histological diagnoses (RCC and ccRCC) as the general cohort; however, US-born HLs were diagnosed with spindle cell carcinoma almost twice as much as foreign-born HLs (10.27% vs. 5.36%). Lastly, 85% of US-born HLs received treatment after diagnosis of mRCC compared to 78.9% of foreign-born HLs; however, at the last update, 47.17% and 32.95% were alive, respectively. Conclusions: In this cohort of patients with mRCC, 1 of 10 patients diagnosed with mRCC was HL. While characteristics were similar between groups, HLs had differences regarding access to care. Even amongst HLs, the country of origin affected the age of diagnosis, treatments, and outcomes. Further histopathologic and clinical characteristics will be presented at the meeting, along with treatment choices, outcomes, and clinical trial participation in the NHL and HL cohorts.

Cutaneous spindle cell carcinoma compressing the trachea in a nosocomephobic patient

An 86 year-old woman was admitted in the emergency unit with a severe deterioration of her general condition. She was found

PO-01-107 INTRA-CARDIAC SPINDLE CELL CARCINOMA FOLLOWING CATHETER ABLATION OF ATRIAL FIBRILLATION AND LEFT ATRIAL APPENDAGE CLOSURE

Spindle cell carcinoma (SpCC), a type of squamous cell carcinoma (SCC), is a rare tumor with features similar to sarcoma that often arises from the respiratory system. Myocardial involvement of these tumors has not been described. We present a case of metastatic SpCC diagnosed through routine transesophageal echocardiography (TEE) following left atrial appendage occlusion (LAAO). To describe a rare occurrence of metastatic SpCC diagnosed through routine TEE following LAA occlusion. NA A 61 year old male with a history of coronary artery disease and heart failure presented with persistent symptomatic atrial fibrillation (AF) despite anti-arrhythmic therapy. We performed pulmonary vein isolation (PVI) and during intubation a laryngeal mass was noted. He was diagnosed with T2N0M0 sarcomatoid SCC and had surgery, radiation and chemotherapy (cisplatin). At that time, he was felt to have a favorable 5 year survival prognosis. Six months later he represented with symptomatic AF and underwent repeat PVI. Due to concerns regarding bleeding risk, LAAO was later performed. During follow up TEE at day 45, a new cystic lesion arising from the posterior left atrium and a 2x3cm heterogenous mass associated with the interatrial septum was noted (Figure 1 A-D). CT scan showed new mediastinal masses with extension into the left atrium in the region treated with radiofrequency ablation (Figure 1 E-H). Biopsy revealed SpCC consistent with the initial laryngeal mass. Tumor extending from the perihilar mass and in the fossa ovalis, given the proximity of prior work and prior transseptal puncture, raises the concern for inadvertent iatrogenic spread of tumor and that catheter manipulation facilitated invasion into the LA with the pedunculated mass and seeded the septum. The patient unfortunately continued to decline clinically and shortly thereafter transitioned to comfort care and passed away. We present a case of persistent symptomatic AF in which laryngeal SpCC was diagnosed during initial PVI and rapidly progressive metastatic SpCC diagnosed via TEE in follow up after LAAO. This presentation is concerning for inadvertent iatrogenic spread of tumor from an extracardiac source through PVI. SpCC is more aggressive than typical SCC, however rapid invasion through the chest wall, lung and myocardium within 1.5 months is extremely rare. While primary spindle cell sarcoma of the myocardium has been reported, to our knowledge we report the first case of metastatic SpCC to the heart.

High-grade Spindle Cell Squamous Carcinoma of the Supraglottic Larynx Treated with Definitive Curative Radiation Therapy- A Rare Case Report

Spindle cell carcinoma or sarcomatoid carcinoma is a highly malignant form of squamous cell carcinoma with a low incidence of 2-3% in the larynx. Considering the poor prognosis, early diagnosis and treatment are imperative. This case report describes a high-grade spindle cell carcinoma of the supraglottic larynx treated with definitive radiation therapy.

KEYNOTE—522 and male spindle cell carcinoma of the breast: A case report

Metaplastic Breast Cancer (MBC) is a rare group of tumors often presenting as triple-negative. MBC accounts for less than 1% of all breast cancers with the spindle cell variant comprising less than 0.5%. While rare, spindle cell carcinoma is the commonest subtype in the western world. It has a more aggressive biological behavior with increased risk of recurrence and death due to disease compared to triple negative breast cancers. There is no treatment guideline for management of MBC due to the rarity of the disease. Instead, treatment is theorized based off success with other types of aggressive breast and metaplastic cancers of different tissue. We present the first known case report of male spindle cell carcinoma of the breast treated with KEYNOTE-522 regimen. Therapy included a first phase with pembrolizumab (dose of 200mg) every 3weeks plus paclitaxel and carboplatin and second phase, with four cycles of pembrolizumab with doxorubicin-cyclophosphamide.

TERT Promoter Mutation c.-124C>T Commonly Occurs in Low-Grade Fibromatosis-like Metaplastic Breast Carcinoma.

Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by the proliferation of spindle cells closely resembling fibromatosis, which represents a benign fibroblastic/myofibroblastic breast proliferation. Unlike most triple-negative and basal-like breast cancers, FLMC has a very low potential for metastases, but demonstrates frequent local recurrences. To genetically characterize FLMC. To this end, we analyzed 7 cases by targeted next-generation sequencing for 315 cancer-related genes and performed comparative microarray copy number analysis in 5 of these cases. All cases shared TERT alterations (6 patients with recurrent c.-124C>T TERT promoter mutation and 1 patient with copy number gain encompassing the TERT locus), had oncogenic PIK3CA/PIK3R1 mutations (activation of the PI3K/AKT/mTOR pathway), and lacked mutations in TP53. TERT was overexpressed in all FLMCs. CDKN2A/B loss or mutation was observed in 4 of 7 cases (57%). Furthermore, tumors displayed chromosomal stability, with only few copy number variations and a low tumor mutational burden. We conclude that FLMCs typically show the recurrent TERT promoter mutation c.-124C>T, activation of the PI3K/AKT/mTOR pathway, low genomic instability, and wild-type TP53. In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations.

Abstract P1-05-31: A single center retrospective analysis of 259 cases of metaplastic breast cancer

Abstract Introduction: Metaplastic breast cancer (MBC) is a rare breast tumor.WHO histological classification of breast tumors in 2019 divided MBC into the following seven types: low-grade adenosquamous carcinoma, fibromatoid metaplastic carcinoma, squamous cell carcinoma, spindle cell carcinoma, metaplastic carcinoma with mesenchymal differentiation, mixed metaplastic carcinoma and myoepithelial carcinoma. Based on single center data, this study intends to conduct a detailed analysis of the clinicopathological features, treatment and prognostic factors of MBC. Methods:We collected 259 MBCs treated in our center from 2006 to 2022. The patient’s age, histological type, image feature, tumor size, lymph node metastasis, tumor stage, immunohistochemical information, surgical plan and systemic adjuvant therapy were summarized and considered to explore the factors affecting the overall survival rate (OS) and disease-free survival rate (DFS). T-test and chi-square test were performed on the data. P&amp;lt; 0.05 showed that the difference was statistically significant. Kaplan-Meier survival was used to analyze the long-term efficacy. Results: The incidence rate of MBC in breast cancer patients in our center is about 0.5%. They included 105 cases of squamous cell carcinoma (40.5%), 49 cases of mixed metaplastic carcinoma (18.9%), 41 cases of spindle cell carcinoma (15.8%), 27 cases of metaplasia carcinoma secreting matrix (10.4%), 6 cases of metaplastic carcinoma with mesenchymal differentiation (2.3%), 6 cases of myoepithelial carcinoma (2.3%), 3 cases of low-grade adenosquamous carcinoma (1.2%), 1 case of fibromatoid metaplasia carcinoma (0.4%) and 21 cases of unknown (8.1%). MBC were mainly three negative subtypes, which were 204 cases (78.8%), 41 cases (15.8%) luminal subtypes and 14 cases (5.4%) HER2 positive subtypes. There was no significant difference in the distribution of breast cancer subtypes among different histological types of MBC. There were 63 cases (24.3%) in clinical stage I, 171 cases (66.0%) in stage II, 23 cases (8.9%) in stage III and 2 cases (0.8%) in stage IV. 58 patients underwent core needle biopsy, of which only 7 (12.1%) reported histological types consistent with MBC. Among 154 patients with molybdenum target reports, 59 of them (38.3%) had malignant calcifications. The diagnostic coincidence rates of MRI, ultrasound and molybdenum target were 90.0%, 85.1% and 74.7% respectively. 258 cases of MBC received surgical treatment, including 183 cases of total mastectomy (70.9%), 53 cases of breast conserving surgery (20.5%) and 22 cases of quadrant resection (8.5%); 132 patients (51.2%) underwent axillary lymph node dissection and 93 patients (36.0%) underwent sentinel lymph node biopsy. 24 patients (9.3%) received neoadjuvant chemotherapy, of which only 2 (8.3%) achieved pathological complete remission. 56 patients (21.6%) received adjuvant radiotherapy, with a median of 25 times. 167 patients (64.5%) received adjuvant chemotherapy, and anthracycline sequential paclitaxel was the most commonly used regimen. The median follow-up was 31 months. The five-year DFS was 82.0%, and the five-year OS was 89.4%. Through Cox regression analysis, it was found that patients’ N stage (P=0.036) and receiving anthracycline sequential paclitaxel adjuvant chemotherapy (P=0.004) were independent prognostic factors. Conclusion: The histological types of MBC are complex. MRI is of high value in diagnosis. Conventional CNB is difficult to meet the needs of pathological tissue classification. Patients without lymph node metastasis and receiving anthracycline sequential paclitaxel adjuvant chemotherapy are associated with better prognosis. Through multidisciplinary standardized diagnosis and treatment, there is no significant difference between the prognosis of MBC and the common types of breast cancer. Keyword: metaplastic breast cancer; pathological characteristics; imaging; treatment; prognosis. Citation Format: Douwaner Liu, Jiajian Chen, Shuang Hao, Bingqiu Xiu, Qi Zhang, Liyi Zhang, Guangyu Liu, Zhimin Shao, Jiong Wu. A single center retrospective analysis of 259 cases of metaplastic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-31.

Distant metastasis in head and neck squamous cell carcinoma variants: A population-based study.

Head and neck squamous cell carcinoma (HNSCC) with distant metastasis (DM) has poor prognosis. HNSCC has several histological variants with varying characteristics. We investigated the DM rates and prognoses of patients with DM among the HNSCC variants. We obtained data from 54 722 cases using the Surveillance, Epidemiology, and End Results database. Odds ratios (ORs) for DM and hazard ratios (HRs) for overall survival (OS) were estimated using a logistic regression model and a Cox proportional hazard model, respectively. DM rate was the lowest in verrucous carcinoma and the highest in basaloid squamous cell carcinoma (BSCC) (0.2% and 9.4%, respectively). ORs for DM were 3.63 for adenosquamous carcinoma, 6.80 for BSCC, and 3.91 for spindle cell carcinoma (SpCC). SpCC was significantly associated with a poor OS (HR, 1.61). DM rates differed among the HNSCC variants. The prognosis of metastatic SpCC is worse than that of other metastatic HNSCCs.

Mammary myofibroblastoma: a case report

Background: Myofibroblastoma is a benign mesenchymal tumour which can be challenging to diagnose. It has a range of histological features that overlap with other benign or malignant neoplasms.1 Adjunct testing that demonstrates RB1 loss on immunohistochemistry and monoallelic loss of 13q14 region on FISH can seal the diagnosis of this lesion which is curative with local excision.2,3 Case summary: We report a case of a 45-year-old female who presented with a right breast nodule. A core biopsy showed a stromal spindle cell proliferation and the working diagnosis included myoid hamartoma, fibroepithelial lesion and a spindle cell carcinoma. The excision of the lesion revealed a vaguely circumscribed spindle cell proliferation with spindle cells arranged in fascicles interspersed by hyalinised collagen bundles. The tumour cells were positive on immunohistochemistry for SMA, Desmin and ER but negative for CKAE1/3, B-catenin, S100, CK broad spectrum and p63. It also showed a loss of RB1. The FISH analysis showed a loss of RB1 at 13q14 in 35.5% of the nuclei confirming the diagnosis of a benign myofibroblastoma. Conclusion: The constellation of histological features when supported with monoallelic loss of 13q14 region and RB1 loss on immunohistochemistry confirms the diagnosis of this benign entity preventing unnecessary further management.

Spindle Cell Carcinoma - A Rare Variant of Metaplastic Carcinoma of Breast; A Case Report with Review of Literature

Spindle Cell Carcinoma - A Rare Variant of Metaplastic Carcinoma of Breast; A Case Report with Review of Literature

Multimodality imaging and histopathology of metaplastic breast cancer

Metaplastic breast cancer (MBC) is a rare subtype of invasive breast cancer characterized by mixed epithelial and mesenchymal differentiation. Commonly seen subtypes include squamous cell carcinoma, spindle cell carcinoma, and metaplastic carcinoma with heterologous mesenchymal differentiation. MBC tends to have a more aggressive clinical presentation, higher metastatic potential, higher rates of local recurrence, and a worse prognosis compared with invasive breast carcinoma of no special type. Most MBCs are triple-negative breast cancers, which explains their resistance to most systemic therapies. Therefore, accurately diagnosing MBC early is crucial for deciding the treatment strategy and predicting the prognosis. In this pictorial essay, the imaging findings of MBC in different modalities and the histopathologic features of its subtypes are reviewed.

Mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a unique neoplasm attributing to less than 1% of all renal cell carcinoma (RCC). The median age is 6th decade with a significant female preponderance.1 These tumors classically consist of tightly packed, elongated, and anastomosing tubules which merge with bland spindle cells in a myxoid stroma in variable proportions. Tubules with tufting or small papillae and foci of foamy macrophages may occur. The tumor cells are low-grade and may show clear cytoplasm or oncocytic changes with rare mitosis. Immunohistochemically, PAX8, CK7, AMACR, and CD10 are positive in this tumor.1,2 Though it is a morphological diagnosis, it can be challenging to differentiate from a solid variant of papillary RCC, sarcomatoid RCC, or myoid-predominant angiomyolipoma. Immunohistochemistry may be of little help due to overlapping profiles.3 Copy number analyses can help establish a diagnosis in challenging cases or core biopsies since these are associated with multiple chromosomal losses involving chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. Novel biomarkers like VSTM2A overexpression are also emerging, which can be detected by RNA in-situ hybridization. Recurrent Hippo pathway aberrations have been defined as the molecular signature of MTSCC with increased nuclear YAP1 protein expression.4 Adverse features such as necrosis, solid growth, single file infiltration, sarcomatoid transformation, lymphovascular invasion, and increased mitoses are indicators of metastatic disease. Although it has indolent behavior, rare cases with classic morphology have been seen to develop metastases.5-6 We describe gross and histopathological findings of mucinous tubular and spindle cell carcinoma in a 65-year-old male patient. He presented with right abdominal pain for one month. The pain was dull and mild to moderate in intensity. On contrast-enhanced ultrasound, a well-defined, smoothly marginated heterogeneous hyperechoic lesion measuring 5.5x6cm was noted at the upper pole of the right kidney. The lesion was hyper enhancing compared to the rest of the renal parenchyma. Based on the radiological findings, possibilities of chromophobe RCC and oncocytoma were considered. The abdominal computed tomography (CT) revealed a hyperdense lesion in the upper pole of the right kidney with a relatively well-defined margin measuring 63x65x69mm with no evidence of significant post-contrast enhancement in the either arterial, venous or delayed phase. The patient underwent a right radical nephrectomy. On gross examination, a well-encapsulated mass was seen wholly occupying the upper pole of the kidney measuring 6.9x6.5x5.5cm. The cut surface was variegated with grey-white, firm areas admixed with mucinous and hemorrhagic foci (Figure 1A). No capsular breach or perinephric fat extension was noted. The renal pelvis, sinus, and renal vessels were free of tumor. Figure 1 A - gross nephrectomy specimen showing a large, well-demarcated tumor involving the upper pole of the kidney measuring 6.9x6.5x5.5cm. The cut surface is variegated and appears grey-white and firm, along with intervening mucinous and hemorrhagic areas (scale bar = 5 cm); B - microscopically, the tumor is well-circumscribed with sharp demarcation from adjacent normal renal parenchyma (H&E; 40x); C - the dominant epithelial component is seen against the background stroma containing significant extracellular mucin (H&E; 100x); D - higher magnification showing tightly packed anastomosing tubules lined by low-grade cuboidal cells with cytoplasmic vacuoles against mucinous background (H&E; 400x).: Microscopically, the tumor was well-demarcated from the adjacent native renal parenchyma (Figure 1B). It was composed of the dominant epithelial element against the background of extracellular mucinous stroma (Figure 1C). The epithelial component contained tightly packed, elongated, tufted, and anastomosing tubules lined by low-grade cuboidal cells and are seen merging with bland spindle cells (Figure 1D). The nuclei display fine vesicular chromatin, inconspicuous nucleoli, and moderate cytoplasm with vacuolations. Mitotic figures are infrequent (<1/10HPF). No necrosis, lymphovascular invasion, or high-grade transformation was found. However, foamy macrophage collections and lymphoid aggregates are admixed. Cholesterol clefts with focal foreign body giant cell response indicated the long-standing nature of the tumor. Based on the gross and microscopy findings, the diagnosis of mucinous tubular and spindle cell carcinoma [(pT1bpNx; American Joint Committee on Cancer (AJCC) staging manual; 8th edition)] was rendered.

Spindle Cell Carcinoma Arising in Xeroderma Pigmentosum-A Rare Tumour in a Rare Disease.

Dear Editor, Xeroderma pigmentosum (XP) is recognized by cutaneous photosensitivity to ultraviolet radiation leading to pigmentary changes, photophobia, and tendency to develop malignancies such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.[12] Spindle Cell Carcinoma (SpCC) is an extremely rare variant of SCC. A case of extremely rare spindle cell squamous cell carcinoma (SpSCC) developing in the setting of XP on the cheek of a 9-year-old boy is presented here. A 9-year-old boy, known case of XP, presented to the hospital with an erythematous nodule on the cheek [Figure 1] of size 3 × 3 cm. The patient also had multiple brown to black lentigines of size 0.1 × 0.1 cm intermixed with hypopigmented macules of size 0.1 × 0.1 cm to 0.4 × 0.4 cm over photo exposed areas of the face, neck, chest, upper back, bilateral upper and lower limbs, palms, and soles. A provisional diagnosis of BCC was rendered, nodule excised, and sent for histopathological examination. Microscopic sections revealed a biphasic tumor composed of atypical squamous cells with the presence of squamous pearls in the superficial part of the biopsy [Figure 2]. The deeper part of the lesion exhibited spindle cells in fascicles with greater atypia and the presence of atypical mitosis (2–3/10 high power fields) [Figure 3]. The transition from the squamous cell to spindled cell was quite prominent [Figure 4]. No necrosis was noted. On immunohistochemistry (IHC), there was co-expression of cytokeratin (CK) [Figure 5a] and vimentin [Figure 5b]. The tumor cells were negative for S100 and HMB45. A histopathological diagnosis of SpCC was rendered.Figure 1: Erythematous nodule over the right cheek near-eye with central black crustingFigure 2: Atypical squamous cells with the presence of squamous pearls. (H and E, ×400)Figure 3: Spindled areas with greater atypia. (H and E, ×400)Figure 4: Transition of atypical squamous cells into spindle cells (H and E, ×40)Figure 5: (a) Cytokeratin expression in squamoid areas (IHC, ×400). (b) Vimentin expression in spindled areas (IHC, ×400)The basic defect in XP is the deficient repair of DNA damaged by UV radiation making XP a model disease for sun-induced carcinogenesis. Damaged DNA is removed with the help of NER replaced by new DNA.[3-5] SpCC is a rare poorly differentiated variant of SCC, which portends a worse prognosis compared to the usual SCC. Seen mostly in men in the sixth and seventh decades, it accounts for 1% of all SCCs and mostly is found in the oral cavity, larynx, pharynx. and sinonasal locations. Primary SpSCC of the skin is extremely rare.[5] Exposure to ultraviolet radiation is one of the most important etiological factors in the development of SpSCC. It usually occurs in the backdrop of solar elastosis and lacks keratinization. Exposure to ultraviolet radiation coupled with DNA repair defects possibly made this patient extremely vulnerable to this aggressive neoplasm.[25] The histological diagnosis is quite challenging. The absence of basaloid cells, peripheral palisading, and retraction clefts excluded BCC. Keratoacanthoma was excluded as there was the absence of a keratin-filled central crater surrounded by the epidermal lip. The presence of invasion into the subcutis, absence of actinic changes, and presence of a connection to the overlying epidermis and positivity for CK ruled out atypical fibroxanthoma. Different theories have been proposed to explain the origin of SpCC. It could possibly arise as a result of dedifferentiation of the spindle cells to the epithelial component. The second theory supports the theory of collision tumors and lastly, some studies report that the spindle component may be a reactive proliferation of the stroma.[15] Thus, XP is a rare disease and SpSCC developing in its backdrop further makes it challenging to timely diagnose and manage the condition. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Metaplastic Breast Carcinoma: A Case Series with Three Different Presentations

Metaplastic Breast Carcinoma (MBC) is one among the rare types of breast carcinoma. MBC was recognised as a separate entity by World Health Organisation (WHO) in 2020. According to WHO, metaplastic carcinoma is classified into six types based on the histology which includes: low grade adenosquamous carcinoma; fibromatosis like metaplastic carcinoma; squamous cell carcinoma; spindle cell carcinoma; carcinoma with heterologous mesenchymal differentiation; and mixed metaplastic carcinomas. This rare type of tumour shows both epithelial and/or mesenchymal elements within the same lesion. The management of these patients remains an enigma due to the rarity of the tumour and the treatment responses between patients following therapy. In the present case series, five cases of MBC and their follow-up have been described. All patients were females within the age group of 50-65 years. All five patients underwent modified radical mastectomy. Lymph node involvement was noted in one case. Among the five cases, two patients had adenosquamous carcinoma, two patients had metaplastic carcinoma with heterologous mesenchymal differentiation and one patient had mixed metaplastic carcinoma.

Molecular Pathways, Targeted Therapies, and Proteomic Investigations of Colorectal Cancer.

According to the GLOBOCAN 2020 data, colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death. The risk factors for colorectal cancer include a diet abundant with fat, refined carbohydrates, animal protein, low fiber content, alcoholism, obesity, long-term cigarette smoking, low physical activity, and aging. Colorectal carcinomas are classified as adenocarcinoma, neuroendocrine, squamous cell, adenosquamous, spindle cell, and undifferentiated carcinomas. In addition, many variants of colorectal carcinomas have been recently distinguished based on histological, immunological, and molecular characteristics. Recently developed targeted molecules in conjunction with standard chemotherapeutics or immune checkpoint inhibitors provide promising treatment protocols for colorectal cancer. However, the benefit of targeted therapies is strictly dependent on the mutational status of signaling molecules (e.g., KRAS) or mismatch repair systems. Here it is aimed to provide a comprehensive view of colorectal cancer types, molecular pathways associated, recently developed targeted therapies, as well as proteomic investigations applied to colorectal cancer for the discovery of novel biomarkers and new targets for treatment protocols.