Variant Of Carcinoma Research Articles

Cytology of micropapillary mucinous carcinoma: A case report of a clinically and genetically distinct breast carcinoma variant.

Micropapillary mucinous carcinoma (MPMC) is an uncommon histopathological variant of breast cancer accounting for approximately one-fifth of all mucinous breast carcinomas. In contrast to pure mucinous carcinoma, MPMC tends to affect younger women and is associated with decreased progression-free survival, higher nuclear grade, lymphovascular invasion, lymph node metastasis, and positive HER2 status. Typically MPMC histology shows micropapillary architecture with "hobnailing" of cells and reverse polarity. Very few publications document the cytomorphological findings of MPMC. We report a case of MPMC that was suspected in fine needle aspiration cytology (FNAC) and confirmed at histopathology.

HER2 Amplification in p53-Mutated Endometrial Carcinomas

p53-mutated endometrial carcinomas tend to recur and develop distant metastases. Therefore, the detection of new potential therapeutic targets such as HER2 is particularly interesting. In this retrospective study, which considered over 118 endometrial carcinomas, the p53 mutation was detected in 29.6% of cases. In these cases, the HER2 protein profile was studied via immunohistochemistry, and an overexpression of HER2 protein (++ or +++) was noted in 31.4%. The CISH technique was used in these cases to determine if gene amplification was present. In 18% of cases, the technique was not conclusive. Amplification of the HER2 gene was observed in 36.3% of cases and 36.3% of cases showed a polysomal-like aneusomy for centromere 17. Amplification was found in serous carcinomas, clear cell carcinomas and carcinosarcomas, highlighting the future potentiality of HER2-targeted therapies in these variants of aggressive carcinomas.

New WHO classification 2022: urinary bladder cancer

The new World Health Organization (WHO) classification of urogenital tumors is still primarily based on anatomic location, but is also a hierarchical taxonomic classification without separate chapters for tumors of the upper urinary tract and the urethra. It clarifies aspects regarding grading and noninvasive entities. It consolidates the use of the Paris system for urinary cytology as well as various subtypes/special types of neoplasms, and incorporates general concepts of the 5th edition of the WHO blue book. In addition to mesenchymal tumors, well-differentiated neuroendocrine tumors and neuroendocrine carcinomas are addressed in separate chapters. Papillary non-invasive low- and high-grade carcinomas and carcinoma in situ remain, while dysplasia and urothelial proliferation of unknown malignant potential (UPUMP) are no longer treated as separate entities. Former variants of urothelial carcinoma are now called subtypes and aberrant differentiation and special types are more precisely defined.

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.

Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance.

The clear cell variant of renal cell carcinoma (ccRCC) is the most common renal epithelial malignancy and responsible for most of the deaths from kidney cancer. Patients carrying inactivating mutations in the Von Hippel-Lindau (VHL) gene have an increased proclivity to develop several types of tumors including ccRCC. Normally, the Hypoxia Inducible Factor alpha (HIF-α) subunits of the HIF heterodimeric transcription factor complex are regulated by oxygen-dependent prolyl-hydroxylation, VHL-mediated ubiquitination and proteasomal degradation. Loss of pVHL function results in elevated levels of HIF-α due to increased stability, leading to RCC progression. While HIF-1α acts as a tumor suppressor, HIF-2α promotes oncogenic potential by driving tumor progression and metastasis through activation of hypoxia-sensitive signaling pathways and overexpression of HIF-2α target genes. One strategy to suppress ccRCC aggressiveness is directed at inhibition of HIF-2α and the associated molecular pathways leading to cell proliferation, angiogenesis, and metastasis. Indeed, clinical and pre-clinical data demonstrated the effectiveness of HIF-2α targeted therapy in attenuating ccRCC progression. This review focuses on the signaling pathways and the involved genes (cyclin D, c-Myc, VEGF-a, EGFR, TGF-α, GLUT-1) that confer oncogenic potential downstream of the VHL-HIF-2α signaling axis in ccRCC. Discussed as well are current treatment options (including receptor tyrosine kinase inhibitors such as sunitinib), the medical challenges (high prevalence of metastasis at the time of diagnosis, refractory nature of advanced disease to current treatment options), scientific challenges and future directions.

Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre.

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. BRAF alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of BRAF non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. BRAF mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other BRAF non-V600E alterations. BRAF non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that BRAF non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that BRAF non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the BRAF mutations were concomitant with other molecular alterations, such as TERT promoter mutation.

Intraosseous mucoepidermoid carcinoma of mandible - A rare menace in mandible

Salivary gland tumors makes up 3–4% of all head and neck cancers, mucoepidermoid carcinoma is a malignant locally recurrent variant of salivary gland carcinoma. .In this short communication we are presenting a rare entity of mandible “intramedullary mucoepidermoid carcinoma” treated with wide local excision (composite resection) with modified radical neck dissection followed by reconstruction with free fibula osteocutaneous flap.

A Case of Fibrolamellar Hepatocellular Carcinoma at the High Specialty Hospital of Veracruz, Mexico

Fibrolamellar hepatocellular carcinoma is a primary hepatic malignancy, primarily affecting adolescents and young adults without underlying liver disease. We present the case of a 22-year-old male farmer who presents burning pain in the epigastrium with an intensity of 2/10 on the VAS scale, on palpation with the presence of a tumor in the right hypochondrium with ultrasound of the liver and bile ducts with evidence of liver mass in the segment VIII, in addition to exploratory laparoscopy with the discovery of multiple implants in 70% of the liver surface. In the histopathological analysis with morphological findings compatible with fibrolamellar carcinoma. In the laboratory with AST 356 UI/L, ALT 205 UI/L, GGT 930 U/L, LDH 343 UI/L AF 638 UI/L, for which treatment was started with atezolizumab 1200 mg and bevacizumab 1000 mg. Continuing to follow up. Fibrolamellar hepatocellular carcinoma is a variant of hepatocellular carcinoma, which usually presents with non-specific symptoms. The imaging approach is fundamental in the diagnosis, being the anatomopathological confirmation. Despite being low frequency tumors, they should be suspected in all young patients with a palpable mass in the liver.

Nomogram for preoperative prediction of high-volume lymph node metastasis in the classical variant of papillary thyroid carcinoma.

The objective of our study was to construct a preoperative prediction nomogram for the classical variant of papillary thyroid carcinoma (CVPTC) patients with a solitary lesion based on demographic and ultrasonographic parameters that can quantify the individual probability of high-volume (>5) lymph node metastasis (HVLNM). In this study, a total of 626 patients with CVPTC from December 2017 to November 2022 were reviewed. Their demographic and ultrasonographic features at baseline were collected and analyzed using univariate and multivariate analyses. Significant factors after the multivariate analysis were incorporated into a nomogram for predicting HVLNM. A validation set from the last 6 months of the study period was conducted to evaluate the model performance. Male sex, tumor size >10 mm, extrathyroidal extension (ETE), and capsular contact >50% were independent risk factors for HVLNM, whereas middle and old age were significant protective factors. The area under the curve (AUC) was 0.842 in the training and 0.875 in the validation set. The preoperative nomogram can help tailor the management strategy to the individual patient. Additionally, more vigilant and aggressive measures may benefit patients at risk of HVLNM.

Invasive Micropapillary Urothelial Carcinoma: an Uncommon and Underreported Variant in Cystectomy Specimens.

Conventional urothelial carcinoma is the most common histological type of urinary bladder carcinoma. The latest edition of the WHO classification of tumours of the urothelial tract lays special emphasis on the ability of urothelial tumours to exhibit divergent differentiation with multiple histologic variants and a diverse genomic landscape. The presence of a micropapillary component (MPC) in urothelial carcinoma is associated with high-grade disease and poor response to intravesical chemotherapy. The present study aims to enumerate the clinicohistological features of urothelial carcinomas with micropapillary differentiation. Slides from 144 radical cystectomy specimens received over 6 years were reviewed independently by two pathologists. A predominant histological pattern along with co-existing pathology was noted. Of these, five cases were pure micropapillary carcinomas, four had conventional urothelial carcinoma with a MPC, one had a microscopic tumour at the mucosal surface, and two cases showed micropapillary histology in the lymph node metastasis, following transurethral resection of bladder tumour and Bacillus Calmette-Guerin therapy. The tumours with pure micropapillary carcinoma presented with a higher pathological stage and poor overall survival. Organ and lymph node metastasis was noted in five and eight cases, respectively, of which six showed a micropapillary pattern in the lymph nodes. Micropapillary urothelial carcinoma is a rare and aggressive variant of urothelial carcinoma with unique histologic features. This variant is often missed and underreported in biopsy and surgical resection specimens. Since the presence of MPC confers a poorer prognosis, the identification and reporting of this entity are important.

Low-grade oncocytic tumour (LOT) of the kidney is characterised by GATA3 positivity, FOXI1 negativity and mTOR pathway mutations.

Aims: We present a 5-case series of low-grade oncocytic tumour of the kidney to further discuss their clinicopathological characteristics. Methods and results: Five patients were included in this study. There were three females and two males aged 45-66years, with a median age of 65years. Four tumours were located in the right kidney, and one was located in the left kidney. Most of the tumour sections were yellow-brown in colour. Tumour sizes ranged from 2.5 to 4.5cm, with a median size of 3cm. Microscopically, the tumours were well-circumscribed but lacked a fibrous capsule; the tumours consisted of monomorphous oncocytic cells arranged mainly in solid and nested architectural patterns. The tumour cells had uniformly round to oval nuclei and often had perinuclear halos but lacked significant irregularities. Immunohistochemically, the tumour cells showed a diffuse and strong positivity for CK7 and were negative for CD117. The tumour cells were also positive for GATA3, E-cadherin, Pax-8, Succinate dehydrogenase B (SDHB) and Fumarate hydratase (FH), and negative for vimentin, Carbonic anhydrase 9 (CA9), CD10, P504s, CK20, TFE3, TFEB, HMB45, ALK and Forkhead box protein I1 (FOXI1). Next-generation sequencing identified genetic variations in these tumours, including MTOR gene mutations (4/5) and PIK3CA gene mutation (1/5). All patients were alive without disease progression at a median follow-up of 32months (range 10-57months). Conclusion: LOT is an emerging renal entity of indolent behaviour that has morphologic overlap with some renal tumours with eosinophilic cytoplasm, primarily with oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma. Familiarity with the distinctive morphological features, immunophenotype and molecular genetics of LOT helps avoid misdiagnosis.

Chromosomal Aberrations Accumulate during Metastasis of Virus-Negative Merkel Cell Carcinoma

Merkel cell carcinoma is a rare, aggressive skin tumor initiated by polyomavirus integration or UV light DNA damage. In New Zealand, there is a propensity toward the UV-driven form (31 of 107, 29% virus positive). Using archival formalin-fixed, paraffin-embedded tissues, we report targeted DNA sequencing covering 246 cancer genes on 71 tumor tissues and 38 nonmalignant tissues from 37 individuals, with 33 of 37 being negative for the virus. Somatic variants of New Zealand virus-negative Merkel cell carcinomas partially overlapped with those reported overseas, including TP53 variants in all tumors and RB1, LRP1B, NOTCH1, and EPHA3/7 variants each found in over half of the cohort. Variants in genes not analyzed or reported in previous studies were also found. Cataloging variants in TP53 and RB1 from published datasets revealed a broad distribution across these genes. Chr 1p gain and Chr 3p loss were identified in around 50% of New Zealand virus-negative Merkel cell carcinomas, and RB1 loss of heterozygosity was found in 90% of cases. Copy number variants accumulate in most metastases. Virus-negative Merkel cell carcinomas have complex combinations of somatic DNA-sequence variants and copy number variants. They likely carry the small genomic changes permissive for metastasis from early tumor development; however, chromosomal alterations may contribute to driving metastatic progression.

A Rare Case of Nodular Goiter Presenting as Follicular Variant of Papillary Thyroid Carcinoma

A Rare Case of Nodular Goiter Presenting as Follicular Variant of Papillary Thyroid Carcinoma

The Versicolour Gyre-Squamous Cell Carcinoma-Anal Canal: A Mini Review

Squamous Cell Carcinoma (SCC) of anal canal is a frequently discerned malignant neoplasm confined to the anal tract. Thus denominated by World Health Organization (WHO), the neoplasm exemplifies primary squamous cell carcinoma of anus. Basaloid variant of squamous cell carcinoma is additionally designated as cloacogenic or transitional cell carcinoma of anal canal. Besides, mucoepidermoid carcinoma of anal canal denominates neoplasms delineating prominent features of mucinous transition.

Comprehensive profile and contrastive analysis of circular RNA expression in cervical squamous carcinoma and adenocarcinoma.

Numerous studies have shown circular RNA (circRNA) dysregulation is associated with the pathogenesis of cervical cancer,particularly in individual carcinoma variants. The aim of this study is to investigate and contrastively analyze the expression pattern of circRNAs in cervical squamous carcinoma and adenocarcinoma mediated by human papillomavirus type 16 (HPV-16). The expression of circRNAs in cervical squamous carcinoma (SCC), adenocarcinoma (ADC) and adenosquamous carcinoma (ASC) tissues, together with the adjacent normal tissues (ANT), was profiled by high-throughput RNA sequencing (RNA-seq). Bioinformatics analysis and quantitative real time polymerase chain reaction (qRT-PCR) validation of the sequencing data were performed. A network of circRNA-miRNA (microRNA)-mRNA was then constructed according to predicted targets and function of candidate circRNAs. A total of 11,685 annotated circRNAs were identified in six cervical samples. There were 42 up-regulated and 98 down-regulated circRNAs. 215 circRNAs were up-regulated in SCC but down-regulated circRNAs in ADC, while 50 circRNAs displayed the opposite trend. Function enrichment analysis based on different expressions of circRNAs found that the most enriched pathway in all the three pathologic variants of cervical cancer was the "ubiquitin mediated proteolysis" pathway. Eight key candidate circRNAs derived from this pathway were further validated, and we noticed that several target miRNAs of candidate circRNAs could target the source genes. Based on this we constructed a related competing endogenous RNA (ceRNA) network. Through a comprehensive interpretation of differentially expressed circRNAs in different pathologic variants of cervical cancer, this study provides new insights into the process of tumor differentiation mediated by HPV. Our results may help to complement the molecular typing and stem cell theory of cervical cancer.

Clear-cell Variant of Mucoepidermoid Carcinoma Presenting as a Palatal Mass in a 10-Year-old Boy.

The clear-cell variant of mucoepidermoid carcinoma (MEC) involving minor salivary glands is extremely rare in children. We report a case of clear-cell variant MEC in the minor salivary gland in a 10-year-old boy who presented with a mass of the right hard palate. Fine-needle aspiration showed features suggestive of clear-cell variant of MEC. Microscopically, the tumor cells showed predominant clear cells and scattered mucous cells. There was increased mitotic activity (6/mm2). No tumor necrosis or nuclear pleomorphism was identified. The tumor cells were positive for cytokeratin 7 (CK7), tumor protein p63, P40 (ΔNp63), CK5/6 and mucicarmine. Rearrangement of mastermind-like transcriptional coactivator 2 (MAML2) (11q21) gene was present in the tumor cells by fluorescence in situ hybridization, supporting the diagnosis of an intermediate-grade clear-cell variant of MEC. A right infrastructure maxillectomy for palate carcinoma with negative margins was performed. Grossly, the tumor was a 2.1 cm well-circumscribed, friable, pale tan mass with focal areas of cystic change. The final pathological diagnosis was clear-cell variant of MEC, intermediate grade, pT2. Post surgery, the patient recovered and was doing well, with no tumor recurrence or metastasis at the 6-month follow-up. To the best of our knowledge, this is the first documented case of clear-cell variant MEC in a child. Due to low to intermediate tumor grade, an overtly aggressive treatment should be avoided in a child.

Solid Variant of Adenoid Cystic Carcinoma Coexisting with Invasive Squamous Cell Carcinoma in Uterine Cervix – A Case Report with Immunoprofile

Primary adenoid cystic carcinoma of cervix is a rare entity. Co-existence of adenoid cystic carcinoma with squamous cell carcinoma is even more rare. Here we present the case of an 85 year old postmenopausal lady who presented with on and off vaginal bleeding and was found to have a hard cervical mass. Hysterectomy with bilateral salpingo-oophorectomy was done and histopathological evaluation revealed coexisting solid variant of adenoid cystic carcinoma and squamous cell carcinoma. High grade squamous intraepithelial lesion was seen adjacent to invasive squamous cell carcinoma. Adenoid cystic carcinoma was positive for CD117 and squamous cell carcinoma was positive for p63. Both the components were also immunoreactive for p16.

Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: What a Surgeon Should Know.

The inclusion of the less aggressive follicular form of papillary thyroid cancer (PTC) is associated with an increase in the incidence of the condition, with the follicular variant of PTC being the most common of all variants. The majority of individuals with the encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) are treated as though they have classic thyroid cancer, despite the availability of mounting evidence to contradict the aforementioned. According to numerous research, a certain type of noninvasive-EFVPTC (NI-EFVPTC) demonstrated poor histopathologic diagnostic reproducibility and has received aggressive treatment similar to that of a classical thyroid neoplasm. Therefore, to replace the term NI-EFVPC, a new nomenclature for these tumors, called "noninvasive follicular thyroid neoplasm with papillary-like nuclear characteristics" (NIFTP), was introduced in the year 2016. The present paper explores this recently introduced terminology, clinical, histologic, and molecular features, and diagnostic criteria.

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

Rare histological types of bladder carcinoma from a tertiary care hospital: Case reports

Bladder carcinoma is one of the most common urological malignancies with many rare histological variants associated with various prognosis. The recognition of these rare histological variants of bladder carcinoma may be helpful in selecting appropriate therapeutic approach and to predict the prognosis of the patients. We present three such rare entities of urothelial carcinoma with squamous differentiation, squamous cell carcinoma of bladder and metastatic bladder carcinoma which are associated with bad prognosis.