High-grade Variant Research Articles

Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype.

Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse group of tumours with distinct features. This study aims to examine the clinicopathological and prognostic features of different variants of ILC, with a particular focus on characterising aggressive subtypes. A large (n = 7140) well-characterised and histologically reviewed BC cohort with treatment and long-term follow-up data was investigated. The cohort was classified based on the WHO classification of tumours into main histological subtypes, including ILC and IDC-NST. ILCs were further classified into variants. Clinicopathological parameters and patient outcomes in terms of BC-specific survival (BCSS) and disease-free survival (DFS) were evaluated. ILC constituted 11% of the cohort. The most common non-classic ILC variants were pleomorphic (pILC) and solid (sILC), constituting 19% of ILC. Compared to classic and related variants (alveolar, trabecular, papillary, and tubulolobular; cILC), pILC and sILC variants were associated with aggressive tumour characteristics. The histologic grade of ILC was an important prognostic variable. The survival patterns identified an aggressive ILC subtype encompassing pILC and high-grade sILC. These tumours, which comprised 14% of the cases, were associated with clinicopathological characteristics of poor prognosis and had high BC-specific death and recurrence rates compared not only to cILC (p < 0.001) but also to IDC-NST (p = 0.02) patients. Contrasting this, cILC patients had significantly longer BCSS and DFS than IDC-NST patients in the first 10 to 15 years of follow-up. Adjuvant chemotherapy did not improve the outcome of patients with aggressive ILC subtypes. pILC and high-grade sILC variants comprise an aggressive ILC subtype associated with poor prognostic characteristics and a poor response to chemotherapy. These results warrant confirmation in randomised clinical trials.

Abstract PO3-03-04: Metaplastic breast cancer: a single center retrospective study

Abstract Background: Metaplastic breast cancer (MBC) is a rare malignancy that accounts for up to 1% of all primary invasive breast carcinomas (BC). It is histologically heterogeneous, usually presents with a triple-negative phenotype and comprises low-grade and high-grade (HG) variants. HG variants have a higher risk of recurrence and a shorter disease-free and overall survival compared to other BC subtypes. Our research aimed to estimate the prevalence of HG-MBC among the Slovenian population and determine the characteristics of patients (pts) and tumours and the disease outcome. Patients and methods: Our retrospective study included pts diagnosed with HG-MBC at the Institute of Oncology Ljubljana from January 1983 until January 2021. Clinicopathologic characteristics such as tumour subtype, size and grade, nodal status, hormonal receptors (HR) and HER-2 status, lymphovascular invasion (LVI), tumour-infiltrating lymphocytes (TIL) and presence of germline BRCA mutation status were determined. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model examined the association between risk factors and survival outcomes. Results: We evaluated 113 HG-MBC pts among a total of 27700 pts diagnosed with BC over 38 years (0.41%). The median age was 61.6 years (range 29.7 -93.9), majority of pts were postmenopausal (78.69%). The median follow-up was 15.5 years. The most common tumour subtype in our cohort was mixed MBC (53 cases, 46.9%), followed by MBC with mesenchymal differentiation (24 cases, 21.2%), squamous cell carcinoma (20 cases, 17.7%) and spindle cell carcinoma (16 cases, 14.2%). From the 113 evaluated pts, we obtained data about the stage in 105 pts, pathological tumour size in 100 pts, number of positive lymph nodes in 99 pts, HR status in 95 pts, HER2 status in 76 pts, grade in 97 pts, LVI in 85 pts, MIB-1 in 41 pts and TIL in 77 pts. At diagnosis, 17/105 pts (16.2%) had stage I disease, 59/105 pts (56.2%) stage II, 25/105 pts (23.8%) stage III and 4/105 pts (3,8%) stage IV. Most tumours were poorly differentiated (90/97, 92.2%) without LVI (60/85, 70.6%). Only 6/95 (6,3%) pts had positive HR, 7/76 (9.2%) pts had positive HER-2 status and 8/77(10.4%) pts intensive TIL. Overall, 13 pts were tested for BRCA germline mutation, among which only 1 (7,7%) had BRCA1 mutation. Modified radical mastectomy was the most frequent type of surgery (63.5%); 49.5% of the patients received radiotherapy. In total, 66/113 pts received CT: from 1983 to 2000, 16/36 (44.4%), and after 2000 50/77 (74.9%). In the first period, most pts received CMF (14/16; 87.5%) and anthracyclines and taxanes (27/50; 54%) in the second period. The disease progressed at 37 pts. At 19 pts, new malignancies were found. 55 pts died, 37 of them because of BC. Five- and 10-year disease-free survival (DFS) was 61.7% and 54.1%, while 5-and 10-year overall survival (OS) was 67.1 % and 56.7%, respectively. However, DFS and OS did not differ between the pre-2000 and post-2000 periods. The best outcome was found in pts with squamous cell carcinoma (5- and 10-year DFS 83.5% and 77.0% and 5-and 10- year OS 89.4 % and 83.0%). A subtype of MBC (squamous cell vs other) was the only predictive factor in multivariate analysis for both DFS (HR 0.21; 95% CI 0.05-0.92; p = 0.038 and OS (HR 0.27; 95%CI 0.09-0.78; p = 0.016), no association was seen between survival and tumour size, nodal status, stage, HR and HER2 status, grade, LVI and TILs. Visceral organs were the most common localization of distant metastases (21/37, 56.8%). Metastases in CNS occurred in 9/37 (24.3%) pts. Median OS after the first progression was only 0.9 years. Conclusions: The proportion of HG-MBC in our cohort of pts is 0.41%. Disease outcomes are poor; the 10-year OS of pts with early HG-MBC is only 56.6% and has not improved during the last decades. Squamous cell differentiation predicts a better outcome and is the only independent predictive factor of DFS and OS among HG-MBC pts. Citation Format: Maša Auprih, Gorana Gasljevic, Eva Setina, Anja Zizek, Simona Borstnar. Metaplastic breast cancer: a single center retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-04.

Determining the clinicopathological significance of the VI-RADS ≧4 group: a retrospective study.

The Vesical Imaging Reporting and Data System (VI-RADS) is widely used for predicting muscle-invasive bladder cancer (MIBC). This study aimed to determine the clinicopathological significance of the VI-RADS ≧4 (VI≧4) group. Patients who underwent transurethral resections of bladder tumors during the study period and preoperative magnetic resonance imaging were considered. The patients were pathologically diagnosed with urothelial carcinoma (UC). We first compared the results of patients with VI-RADS scores of 3 and 4 to determine the cut-off score for MIBC; thereafter, the patients were divided into the VI≧4 and VI-RADS ≦3 (VI≦3) groups using VI-RADS. The clinicopathological significance of the VI≧4 group was examined retrospectively by comparing the characteristics of each group. In total, 121 cases were examined, of which 28 were pathologically diagnosed with MIBC. Of the 28 MIBC cases, three (10.7%) had a VI-RADS score of ≦3, and 25 (89.3%) had a VI-RADS score of ≧4. Of the 93 NMIBC cases, 86 (92.5%) had a VI-RADS score of ≦3, and seven (7.5%) had a VI-RADS score of ≧4. The diagnostic performance of the VI-RADS with a cut-off score of 4 was 89.3% for sensitivity, 92.5% for specificity, and an area under the curve (AUC) of 0.91. Contrastingly, for a cut-off score of 3, the sensitivity was 89.3%, specificity was 62.0%, and AUC was 0.72. A VI-RADS score of ≥ 4 could predict MIBC. In the VI≧4 group, 30 of 32 (93.8%) patients had high-grade tumors. The VI≧4 group had significantly more high-grade bladder cancers than the VI≦3 group (p < 0.001 OR = 31.77 95%CI:8.47-1119.07). In addition, the VI≧4 group had more tumor necrosis (VI≧4 vs VI≦3, p < 0.001 OR = 7.46 95%CI:2.61-21.34) and more UC variant cases (VI≧4 vs VI≦3, p = 0.034 OR = 3.28 95%CI:1.05-10.25) than the VI≦3 group. This study suggests that VI-RADS has a high diagnostic performance in predicting MIBC and that VI-RADS could diagnose high-grade tumors, necrosis, and UC variants.

Recent developments in the pathology of primary pulmonary salivary gland-type tumours.

Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland-type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland-type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland-type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type-tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high-grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland-type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland-type tumours of the lung and those primary to other sites.

Epithelioid extragastrointestinal stromal tumor in the pelvic cavity: A rare case at a rare location

ABSTRACT Extraintestinal gastrointestinal stromal tumors (EGISTs) are rare stromal tumors involving mesentery, omentum, and retroperitoneum. EGISTs of the pelvic cavity are extremely uncommon, and till date, no case of pure epithelioid type arising from the pelvic cavity has been reported. They pose a diagnostic pitfall as they may mimic ovarian malignancy. We present a unique case of an epithelioid extraintestinal stromal tumor arising from the pelvic cavity. A 43-43-year-old woman presented with complaints of abdominal pain and menstrual irregularities. Ultrasound examination revealed a large well-defined hypoechoic mass in the right pelvic cavity with a possible site of origin from the right ovary. A total hysterectomy with bilateral salpingo-oophorectomy was done. Histopathological examination revealed an encapsulated tumor comprising predominantly of nests and lobules of epithelioid cells with round-to-oval nuclei, vesicular chromatin, and moderate amount of eosinophilic to clear cytoplasm. Mitotic activity was brisk along with focal areas of necrosis. On immunohistochemistry, tumor cells were diffusely and strongly positive for DOG1 and CD117. They were negative for smooth muscle actin, vimentin, S-100, and HMB-45. Based on these findings, a final diagnosis of the high-grade GIST epithelioid variant was made. It is crucial to make the correct preoperative diagnosis of GIST, since these patients may benefit from neoadjuvant imatinib, especially in case of large tumor size.

Dermatofibrosarcoma Protuberans of the Face.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor with high rate of local recurrence but low metastatic potential. Its high-grade fibrosarcomatous variant and occurrence on the head and neck are rare findings associated with increased morbidity and mortality. The most significant prognostic feature of DFSP is obtaining tumor free surgical margins. As such, accurate recognition and proper management of this uncommon and locally aggressive malignancy is especially crucial in head and neck surgery.

TFG::MET-rearranged soft tissue tumor: A rare infantile neoplasm with a distinct low-grade triphasic morphology.

This article presents 2 cases of TFG::MET-rearranged mesenchymal tumor, an extremely rare molecular subset among an emerging group of mesenchymal neoplasms with kinase gene (NTRK, BRAF, RET and others) alterations. Both tumors were congenital, occurred in female patients and presented as huge masses on the trunk and thigh, measuring 18 and 20 cm in the largest dimension. Both cases showed identical areas with a distinctive triphasic morphology resembling fibrous hamartoma of infancy (FHI), consisting of haphazardly arranged ovoid to spindled cells traversed by variably cellular and hyalinized fascicles admixed with (most likely non-neoplastic) adipose tissue. In other areas, a high-grade infantile fibrosarcoma/malignant peripheral nerve sheath tumor-like (IFS/MPNST-like) morphology was present in both cases. While the first case co-expressed CD34 and S100 protein, the other case did not. When combined with the three previously reported MET-rearranged cases (of which two harbored TFG::MET fusion), 3/5 and 3/4 of MET-rearranged and TFG::MET fusion-associated tumors, respectively exhibited similar triphasic FHI-like low-grade morphology. This points toward the existence of a relatively distinct morphological subset among kinase-fusion-associated tumors which seems to be strongly associated with MET fusions. It seems some of these low-grade cases may transform into a high-grade variant with IFS/MPNST-like morphology as has been observed in other tumors with kinase gene fusions. While most cases seem to follow an indolent clinical course, the recognition of these tumors is clinically relevant as MET tyrosine kinase inhibitors might represent an effective treatment option for clinically aggressive or unresectable cases.

Clear cell variant mucoepidermoid carcinoma of salivary gland in a grey wolf (Canis lupus)

A 14-year-old male grey wolf (Canis lupus) with a history of severe facial swelling was submitted for necropsy. Clinical and radiological examination demonstrated an expansile neoplastic mass in the nasal and frontal sinuses. On necropsy, an amorphous neoplastic mass and extensive necrosis were observed in the nasal turbinate. Microscopic examination revealed a tumour principally composed of obvious clear tumour cells characterised by small hyperchromatic nuclei and abundant clear cytoplasm. These clear cells were positive for mucin with PAS, PAS-D reaction, and alcian blue (pH 2.5) staining, but negative for PTAH staining. Immunohistochemically, some of tumour cells were strongly positive for mesenchymal cells (vimentin), whereas they were negative for myoepithelial antigen (alpha-SMA) and cytokeratin. Based on the histopathological and immunohistochemical features, the present case was diagnosed as high-grade clear cell variant mucoepidermoid carcinoma (MEC). This is the first description of clear cell variant MEC in a wolf.

Using Process Mineralogy as a Tool to Investigate Blending Potential of the Pentlandite-Bearing Ores at the Nkomati Ni Mine in South Africa

The mineralogy and texture of Ni-sulfide ores at the Nkomati nickel mine are highly variable, and this results in often erratic nickel recovery at the mine. The variability of the ore presents an opportunity to study the influence of grind size on the flotation-based recovery of Ni in highly heterogeneous sulfide ores, which would be applicable to this ore type at many other mines worldwide. In view of this, a process mineralogy investigation was conducted on thirteen mineralogically and texturally different nickel-sulfide ores from the Nkomati Nickel Mine, with a view on the influence of grind size on the flotation performance of pentlandite. Ore types presented include medium- and high-grade variants of the bleb, disseminated, massive, semi-massive, and net-textured sulfide ores of the Main Mineralized Zone (MMZ), as well as disseminated chromite-rich nickel sulfide ore and massive chromitite ore of the Peridotitic Chromitite Mineralized Zone (PCMZ). Laboratory scale metallurgical test work, comprising of sequential grinding and bench-top flotation testing of the ores, was conducted in combination with quantitative mineralogical investigation of the flotation feed and associated flotation products, using a FEI 600F Mineral Liberation Analyzer. The ore types under consideration require a variety of grind sizes (i.e., milling times) in order to attain optimal recovery of nickel through flotation. This is predominantly controlled by ore texture, and also partly by the abundance of the major constituent minerals in the ore, being pyroxenes, base metal sulfides, and chromite. Liberation of pentlandite is directly correlated with grind size (milling time), which is also positively correlated with the level of nickel recovery through flotation. A grind size of P80 at 75 µm results in the highest concentrate nickel grades of 7.5–8.1% in the PCMZ ores’ types which is the current grind for the PCMZ ores at Nkomati. A grind size of P77 at 75 µm yields the best overall pentlandite liberation, Ni recoveries of 84–88% and grades of 5.3–5.6% in the MMZ ores. This holds the potential to produce the best overall pentlandite liberation, nickel grades, recoveries from blending the MMZ and PCMZ ore types, and milling the composite ore at a target grind of P80 at 75 µm.

A mesenchymal chondrosarcoma of the right tibia in a young man requires disarticulation of the right knee: A case study

Chondrosarcoma is a malignant tumor occupying the 2nd position in terms of frequency, all ages combined, after osteosarcoma [1]. Epidemiological data extracted from cancer registries in Europe indicate an annual incidence of ~0.1/100,000 inhabitants [2]. Mesenchymal chondrosarcoma of bone is a rare high-grade variant of chondrosarcoma (2-13%), which usually has an extra-skeletal (30-40%) or central intramedullary location (15-30%).

Primary basaloid squamous cell carcinoma of the parotid gland mimicking metastasis of basal cell carcinoma of the contralateral periorbital region: case report

Basaloid squamous cell carcinoma (BSCC) in the head and neck area is extremely rare. World Health Organization defined BSCC as a high-grade variant of squamous cell carcinoma composed both of basaloid and squamous components. Due to its histologic similarity to other parotid gland malignancies it can be easily misdiagnosed. We report first case of BSCC arising from parotid gland in Europe and second in the world literature. A 72-year-old female patient was referred to the Department of Cranio-Maxillofacial Surgery of the Jagiellonian University in Poland due to the tumor arising from the right parotid gland. Patient had history of multiple excisions of recurrent basal cell carcinoma (BCC) of the left periorbital region. We performed total parotidectomy with facial nerve preservation. Postoperative radiotherapy (PORT) was carried out, and the patient received 70 Gy in 30 fractions on the parotid gland area due to the fact that the tumor adhered to the facial nerve trunk and branches, additionally 60 Gy on the neck area in I, II and III levels. To distinguish the tumor of the parotid gland from the possible metastasis from BCC of the left medial canthal region previous histopathological slides were also reexamined and compared with histopathological examination of removed parotid gland tumor. Histological examination confirmed a rare case of BSCC arising from the parotid gland. 14 months of the follow up did not show local recurrence or distant metastasis.

Epithelioid Variant of High-Grade Myxofibrosarcoma in the False Vocal Fold: A Case Report

Myxofibrosarcoma (MFS) is a histologic subtype of malignant fibrous histiocytoma (MFH), with a predominant myxoid component. MFS is characterized by locally aggressive behavior and a high rate of local recurrence, however, with a good prognosis. Head and neck MFS accounts for 3% of all cases of MFS. To date, only two cases of laryngeal MFS have been reported. Owing to the rarity of MFS, the clinical characteristics and optimal treatment options remain controversial. Surgical resection with a clear margin is considered the treatment of choice. Compared to traditional MFS tumors, epithelioid variants have worse prognosis. Other factors associated with a poor prognosis of MFS tumors include inadequate surgical margins, large tumor size, old age, and high-grade tumors. Herein, we report a case of high-grade epithelioid variant MFS located in the false vocal fold, requiring total laryngectomy to obtain an adequate surgical margin. To our knowledge, this is the first case report of epithelioid variant of high-grade MFS presenting in the larynx.

Giant De-Differentiated Liposarcoma of the Ascending Colon – A Rare Entity

Background: Liposarcoma is one of the common malignant mesenchymal tumors of the retroperitoneum and soft tissue of the extremities. Liposarcoma primarily arising from the colon is extremely rare. De-differentiated liposarcoma, a high grade variant has high local recurrence and distant metastatic potential. At present no standard treatment guidelines are established for the colonic liposarcoma in view of the rarity of the condition. Case Presentation: In this article we report a case of 46-year-old female who presented with a large right sided abdominal lump. On cross sectional imaging, she was found to have a large heterogenous exophytic mass arising from the ascending colon. Colonoscopy showed a submucosal lesion of the ascending colon with luminal narrowing. She underwent a right radical hemicolectomy. Histopathology of the resected specimen was reported as a de-differentiated liposarcoma arising from the ascending colon, which is an extremely rare occurrence. Patient made an uneventful recovery and is under follow-up. Conclusion: Liposarcoma is a rare disease of large intestine. It should be considered in the differential diagnosis when there is a large, submucosal colonic swelling with no lymph nodal or peritoneal disease. Complete surgical resection with clear margins is the standard of treatment. Evidence on the benefits of adjuvant chemotherapy and radiotherapy in improving survival in liposarcoma of colon is currently evolving.

Dichotomy in Growth and Invasion from Low- to High-Grade Glioma Cellular Variants.

Glial dysfunction outraging CNS plasticity and integrity results in one of the most dangerous cancers, namely glioma, featuring little median survival period and high recurrence. The hallmark properties of proliferation, invasion and angiogenesis with the infiltrated macrophages in glioma are expected to be tightly coupled or cross-linked, but not properly related so far. The present study is aimed to find a relationship between this featured quadrangle from lower to higher grades (HG) of post-operative glioma tissues and their invading subsets. Elevated Ki67-associated proliferation in lower grades (LG) was supported with VEGF dependent angiogenic maintenance which found a decrease unlikely in HG. In contrast, MMP 2 and 9-associated invasions augmented high in HG with the dominant presence of CD204+ M2 polarized macrophages and a general increase in global DNMT1-associated methylation. Marked differences found in ECM invading cellular subsets of HG showing high proliferative capacity indicating rationally for recurrence, contrasting the nature of gross tumor tissue of the same grade. Thus in LG, the neoplastic lesion is more inclined to its growth while in higher grade more disposed towards tissue wreckage in support with cellular environmental milieu whereas the cellular variants and subsets of invaded cells showed different trends. Therefore, some operational dichotomy or coupling among cellular variants in glioma is active in determining its low- to high-grade transition and aggressive progression.

Primary and Secondary/ Metastatic Salivary Duct Carcinoma Presenting within the Sinonasal Tract

Traditionally, sinonasal adenocarcinomas have been subdivided into intestinal (ITAC) and non-intestinal (non-ITAC) categories. The latter encompasses salivary-type adenocarcinomas originating from the seromucinous glands of the sinonasal mucosa and non-salivary adenocarcinomas. The non-salivary adenocarcinoma category is further subdivided into low-and high-grade variants. Among salivary-type sinonasal adenocarcinomas, tumors recapitulating salivary duct carcinoma (SDC) are exceedingly rare, but some might have been lumped into the high-grade non-ITAC category. To date, only three primary SDCs originating in the sinonasal tract have been reported. We herein describe 7 cases of SDC including one previously reported case (4 primary sinonasal, 3 metastatic/ extension from parotid gland SDC). The primary tumors affected 3 males and one female aged 60 – 75. Different sites were involved by the primary tumors while the secondary tumors affected the sphenoidal (2) and the frontal + maxillary (1) sinuses. Three primary tumors were de novo high-grade SDC and one was confined to contours of a pre-existing pleomorphic adenoma. All 3 secondary tumors were SDC ex pleomorphic adenoma of the parotid with a long history of recurrences, ultimately involving the sinonasal tract. Androgen receptor was positive in 7/7 cases. Four of 6 cases were strongly HER2/neu + (either score 3 + or with verified amplification). This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies.

Acinic cell carcinoma of the salivary gland in the adult and paediatric population: a survival analysis.

Acinic cell carcinoma (AcCC) is a rare malignant neoplasm of the salivary glands and generally considered to be a low-grade tumour. Surgical treatment is often curative, but a more aggressive high-grade variant has been associated with poorer survival and propensity for distant metastasis. No standard treatment guidelines exist and the approach to treatment is varied in the published series. The aim of this study is to present the experience of three major hospitals in Sydney, Australia, in treating AcCC of the salivary gland, with a focus on clinico-pathological features of disease and their associations with survival outcomes. Adult and paediatric cases of AcCC of the salivary gland during the time period 1979-2018 were retrospectively included. Demographic, clinico-pathological, treatment and survival outcome data were extracted. Survival analysis was undertaken to assess the effect of clinical and pathological variables on overall and disease-free survival. Thirty-two cases were reviewed (29 adult and three paediatric). Thirty tumours (93.8%) were parotid gland primary tumours. Mean overall and disease-free survival was 17.0 ± 0.7 and 16.0 ± 0.9 years, respectively. Features associated with poorer survival were cT staging >1, presence of preoperative clinical facial nerve deficit and local recurrence. Positive margins were associated with recurrence. These data suggest that disease-free and overall survival in AcCC of the salivary gland is excellent with surgery as the first-line treatment. Poor survival outcomes are uncommon and may be associated with locally advanced disease in the presence of other well-established high-risk features.

When Should Elective Neck Dissection Be Performed for Parotid Gland Malignancy?

When Should Elective Neck Dissection Be Performed for Parotid Gland Malignancy?

Adjuvant Radiotherapy Improves Overall Survival When Added to Surgery and Chemotherapy for Endometrial Carcinosarcoma: A Surveillance, Epidemiology, and End Results Analysis

Endometrial carcinosarcoma (CS), or malignant mixed Mullerian tumor, is a high-grade variant of endometrial carcinoma with a high risk for recurrence. Adjuvant multi-agent chemotherapy (CHT) is a preferred treatment modality in all stages of disease, with or without radiotherapy (RT). As prospective data are lacking regarding the benefit of RT when added to adjuvant CHT in CS, we sought to analyze the Surveillance, Epidemiology, and End Results (SEER) database to ascertain whether RT improves overall survival (OS) and cancer-specific survival (CSS) when added to surgery and CHT for endometrial CS. SEER 18 Custom Data registries (Nov 2018 submission) were queried for endometrial (ICD10 C54.1-9, C55.9) CS (ICD-0-3 8980-3). Patients with stage I-III CS who received CHT with or without RT were included for analysis. Univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting was performed to account for indication bias. Furthermore, conditional landmark analysis using a minimum follow-up time of 3 months was performed to minimize immortal time bias. A total of 1,541 patients treated from 1988-2016 were included in this analysis. Median age at diagnosis was 65 (IQR 59-71). Patients had FIGO stage IA (30%), IB (14%), II (9%), IIIA (8%), IIIB (3.6%), or IIIC (32%) disease. All patients received CHT and 54% received RT, either with external beam RT (EBRT) alone (25%), EBRT with a brachytherapy boost (9.7%), or brachytherapy alone (18.7%). On UVA, adjuvant RT improved OS (HR 0.65, 95% CI 0.56-0.77, p<0.001) and CSS (HR 0.64, 95% CI 0.54-0.76, p<0.001) compared to surgery and CHT alone. Of note, RT was more likely to be delivered to patients who were slightly younger (p = 0.034) and to those with a lower FIGO stage (p<0.001). After adjusting for these baseline imbalances, the OS benefit provided by adjuvant RT persisted (HR 0.76, 95% CI 0.65-0.89, p<0.001), as did the CSS benefit (HR 0.74, 95% CI 0.63-0.87, p<0.001). Moreover, these findings were maintained using a 3-month conditional landmark analysis (HR 0.67, 95% CI 0.57-0.79). On subgroup analysis, factors associated with an OS benefit included stage IA (HR 0.45, 95% CI 0.45-0.99) and IIIA (HR 0.42, 95% CI 0.24-0.74) disease, grade III disease (HR 0.78, 95% CI 0.61-0.99), ages 50-64 years (HR 0.76, 95% CI 0.59-0.98) and ≥65 years (HR 0.79, 95% CI 0.64-0.98), and treatment delivered between 2010-2016 (HR 0.65, 95% CI 0.52-0.81). In patients with FIGO stage I-III endometrial CS undergoing surgery and CHT, RT improves OS and CSS. Further prospective data are needed to investigate the benefit of RT in endometrial CS treated with modern therapies.

IPSILATERAL SYNCHRONOUS MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA AND CLEAR CELL PAPILLARY RENAL CELL CARCINOMA: A CASE REPORT AND REVIEW OF THE LITERATURE

Renal cell carcinoma (RCC), the most common solid lesion of the kidney, accounts for approximately 2%-3% of all malignancies among adults. Clear cell carcinoma and papillary cell carcinoma are the most common types of renal tumors. Some case reports have described synchronous benign and malignant tumors in the same kidney. In particular, angiomyolipoma and RCC in patients with tuberous sclerosis (TSC) and non-TSC have been reported many times in the literature. However, unilateral concordance of malignant renal tumors is very rare; thus, only few cases have been reported in the literature.Here we report the case of a 58-year-old male who had ipsilateral synchronous mucinous tubular and spindle cell carcinoma (MTSCC) and clear cell papillary renal cell carcinoma (CCPRCC). Both cancers are rare and relatively recently defined subtypes of RCC. Additionally, both were successfully treated using partial nephrectomy. MTSCC has been a distinct entity in the World Health Organization classification of kidney tumors since 2004. The classic type of MTSCC is characterized by small elongated tubules lined with clear cuboidal or spindle cells with mucinous stroma. Neoplastic cells always exhibit low-grade histological features. However, unclassified variants of MTSCC, such as mucin-poor, papillary, high-grade, and sarcomatoid variants, have also been reported. MTSCC is considered to have a relatively good prognosis, but some patients with poor prognoses have recently been reported. CCPRCC is a recently recognized entity and represents the fourth most common variant of RCC. It has unique morphological and immunohistochemical features and shows indolent clinical behavior. Microscopically, CCPRCC may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC, with clear cell changes. In 2006, CCPRCC was described as a subtype of renal tumors in patients with end-stage renal disease. However, currently, CCPRCC has also been shown to occur in kidneys with normal function.To the best of our knowledge, this is the first report of ipsilateral synchronous MTSCC and CCPRCC, which we present with a review of the pertinent literature.

Encapsulated papillary carcinoma of breast; a clinicopathological study of 25 cases and literature review with emphasis on high grade variant

Encapsulated Papillary Carcinoma (EPC) is a rare breast tumor with excellent prognosis. Treatment and stage of EPC is influenced by invasion and high nuclear grade. Our aim was to study the clinicopathological features of EPC, especially high grade tumors and to compare the features of invasive and non-invasive tumors.We reviewed clinicopathological features of 25 cases of EPC diagnosed at our institution from 2006 till 2020. Patients' age ranged from 21 to 75 years (median 55 years). Tumor size ranged from 1 to 9 cm (median 3.5 cm). Overall, invasion was present in 44% cases. High nuclear grade was observed in 24% cases. Majority of these high grade tumors were below 40 years. All of these tumors were 4 cm or larger in size. Two third of these tumors were invasive. Hormone receptor negativity and lymph node involvement was observed in 1 out of 3 cases, when performed. Clinicopathological and histological features of invasive and non-invasive tumors were compared and only lymph node involvement was found to be significantly more frequent in invasive tumors (p = 0.049). Median follow up duration was 18 months. All patients were alive and disease free except for a single patient who died of cerebrovascular accident.EPC has excellent clinical course. Invasion and high nuclear grade should be carefully searched for as these features determine tumor stage and treatment.