Mixed Tumor Research Articles

Immunohistochemical Analysis of Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 and Enolase 1 in Canine Mammary Tumors: Associations with Tumor Aggressiveness and Prognostic Significance

Mammary neoplasms in dogs are a common clinical concern, especially in middle-aged and older intact females. These tumors share similarities with human breast cancer in terms of histology, disease progression, and risk factors, making dogs a relevant model for breast cancer research. The search for biomarkers in canine mammary tumors is essential to understand tumor progression and identify potential therapeutic targets. This study investigated the expression of two potential biomarkers—Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 (ITIH2) and Enolase 1 (ENO1)—in the mammary glands of healthy and tumor-bearing dogs using immunohistochemistry. Both proteins were identified in previous proteomic analyses of extracellular vesicles derived from the plasma of healthy and tumor-bearing dogs. A total of fifty-one canine mammary tissue samples were analyzed and categorized into three groups: (i) the control group, composed of five samples of normal mammary tissue without neoplasia; (ii) benign tumors, composed of nineteen samples of benign mixed tumors; and (iii) malignant tumors, which included six carcinomas in grade 1 mixed tumors, five carcinomas in grade 2 mixed tumors, thirteen solid carcinomas of grade 3, one papillary carcinoma, and two tubular carcinomas. Regarding the intensity of staining, quantified by histoscore, there were no significant differences in the comparison between the groups; for ITIH2, the p-value was 0.33, and for ENO1, the p-value was 0.57. Regarding the predictive potential of their respective ROC curves, the proteins demonstrated low predictive power in canine mammary tumors. These findings indicate that neither ITIH2 nor ENO1 demonstrated strong prognostic value in this setting, as demonstrated by their moderate AUC values, wide confidence intervals, and lack of statistical significance. However, this study found distinct tissue localization patterns for ITIH2 and subcellular localization for ENO1. As an additional way to examine possible associations of these proteins with epithelial–mesenchymal transition, the ZEB1 antibody was tested by both single and double immunohistochemistry, demonstrating a tendency to be more intensely expressed in the malignant group and tending to be associated with ENO1 in canine mammary tumors.

MRI imaging and machine learning based radiomics for detection of mixed HCC and CCA tumors: Still a need for liver biopsy?

531 Background: Primary liver cancer (PLC), comprising hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a leading cause of cancer mortality globally. The combined hepatocellular cholangiocarcinoma (cHCC-CC) subtype may be less common but is relevant to treatment efficacy. We therefore evaluated the diagnostic accuracy of various approaches in distinguishing these liver cancers. Methods: Patients diagnosed with HCC, CCA, and cHCC-CC at Beijing University Cancer Hospital and Institute, China were included. Radiologists of varying expertise independently assessed MRI scans, and we measured their diagnostic consistency. Radiomic features were extracted from MRI scans, and machine learning was applied to differentiate the cancer types. Results: Standard imaging was insufficient to reliably characterize cHCC-CC. Abdominal imaging experts (AIEs) had a higher mean sensitivity for HCC and CCA, 88% and 84% respectively, while non-experts (NIEs) had a lower sensitivity of 50% for HCC and 38% for CCA (HCC: p=0.03, CCA: p=0.008). Radiomic analysis found ‘Sphericity’ and ‘ClusterShade’ as the most relevant features. However, radiomics algorithms were also not sufficient to distinguish cHCC-CC from either HCC or CCA. Regarding sensitivity, the radiomic-based model was not better than radiologists for any of the three classes (p=0.065 for HCC, p=0.426 for CCA, and p=1.0 for cHCC-CC). The random forest algorithm yielded an accuracy of 76% in the test set, since it correctly classified most HCC and CCA, while only one quarter of cHCC-CC tumors. Conclusions: Until improved diagnostic tools are available, biopsy of liver cancer remains critical to the detection, diagnosis, and effective treatment of these cancers.

Ameloblastic Fibroma of the Mandible Presenting as a Dentinoid Formation in an 8-Year-Old Child: A Case Report.

Ameloblastic fibroma is an uncommon, benign, mixed odontogenic tumor characterized by the presence of both epithelial and mesenchymal components, without the formation of hard tissue. It constitutes approximately 1.5%-4.5% of all odontogenic tumors and predominantly affects the posterior mandible. Most cases are observed in individuals under 22 years of age, with a slight predilection for males. The initial presentation typically involves a painless, slow-growing mass, often discovered incidentally during routine radiographic examinations. This lesion carries a risk of recurrence and potential for malignant transformation. We present a case of an 8-year-old female child who presented with a painless swelling in the right posterior mandibular region for 6 months, which was histologically characterized by dentinoid formation.

Tumour size is associated with growth rates of >0.5 cm/year and delayed intervention in small renal masses in patients on active surveillance.

To evaluate the association between tumour size and the growth rate (GR) of small renal masses (SRMs) in patients managed by active surveillance (AS). We queried the prospective, multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry for patients on AS with an imaging interval of ≥6 months, identifying 456 patients. We tracked tumour size over time; a GR >0.5 cm/year was defined as a GR event. We used multivariable recurrent events and time-to-event Cox regression modelling to evaluate the association between tumour size and GR events (primary outcome) and tumour size and delayed intervention (DI; secondary outcome). We tested tumour size as a continuous variable and dichotomised tumour size by predefined (2-cm) and calculated (2.9-cm) cutoffs. We calculated the cutoff using maximally selected rank statistics and time to progression, defined according to the DISSRM registry. The median (interquartile range) follow-up of patients on AS was 40.1 (26.4-71.2) months, during which 128 patients (28%) had ≥1 GR event, and 80 (18%) underwent DI. Larger tumour size was an independent predictor for GR events and DI when tested as a continuous and a dichotomous variable in multivariable analyses (all P < 0.05). The association was strongest when accounting for the change in tumour size over time and when applying the 2.9-cm cutoff. The study is limited by the mixed tumour pathology inert to SRMs. Larger tumour size was independently associated with GR events and DI for patients with SRMs on AS. A 2.9-cm cutoff may provide valuable information for patient counselling.

Multiple Loss of Heterozygosity in a Case of Rare Ovarian Mixed Germ Cell Tumor - Case Report and Overview of Literature

Abstract Malignant germ cell tumors (GCTs) are characterized by pluripotency and exhibit diverse embryonic and extraembryonic structures. Approximately 10% of malignant GCTs are mixed germ cell tumors. The precise histogenic origins of GCTs remain elusive, mostly because of their rare occurrence. The aim of this study is to determine the histogenic origin of an extremely rare mixed germ cell tumor of the ovary consisting of embryonal carcinoma and non-gestational choriocarcinoma components using short tandem repeats genotyping by the quantitative-fluorescence PCR and capillary electrophoresis. The comparison of short tandem repeat profiles between the patient's blood DNA and microdissected tumor revealed a consistent loss of heterozygosity at multiple short tandem repeat loci, indicating a clonal origin for both embryonal carcinoma and non-gestational choriocarcinoma components suggesting a potential origin in abnormal meiotic processes. The presence of loss of heterozygosity in the vast majority of examined loci suggests an origin from aberrant meiosis, possibly due to errors in meiosis I or meiosis II. Due to the rarity of mixed germ cell tumors, it is difficult to assess the clinical significance of this exact histogenic origin. Further studies and meta-analyses of a larger cohort are next essential step to explore the clinical significance of GCT histogenic origins. This article aims to improve the understanding of the GCT etiology.

Mixed Glioneural Tumors Mimicking Gliomas: Two Cases From a Tertiary Care Institute in South India and a Literature Review

Mixed Glioneural Tumors Mimicking Gliomas: Two Cases From a Tertiary Care Institute in South India and a Literature Review

Association of blood group types and clinico-pathological features of gynecological cancers (GCs)

BackgroundGynecological cancers (GCs) affect the reproductive system of females, and are of multiple types depending on the affected organ most common of which are cervical, endometrial, ovarian cancers. Among different risk factors for GCs, ABO blood group system is considered as one of the pivotal contributing factors for increased susceptibility of GCs. The aim of our study was to report on the demographics of GC patients and to investigate the relationship between the ABO blood group system and the risk of acquiring GC in our population.MethodsThe current retrospective cross-sectional study was carried out between the years of 2016 and 2023. The sample included all the patients having age > 18 with a record of blood group and confirmed histological or cytological diagnosis as per International Federation of Gynecology and Obstetrics (FIGO) guidelines. A comprehensive review of the charts was conducted to gather data including demographics, tumor characteristics, comorbidities, adverse effects, and treatment methods.ResultsA total of 543 female patients were included in the study. The mean age of patients was 61.6. The three most common BG in our GC cases were as O + (43.8%), followed by A + (26%), and B + (15.5%). Among comorbidities, hypertension (HTN), diabetes mellitus (DM), dyslipidemia were the top three affecting GC patients. A significant association (p < 0.05) between ABO BG and serous histology in endometrial cancer was found. ABO blood group and fallopian cancer showed a significant relationship between serous histology and B blood group (p < 0.05). For ovarian cancer a significant association between AB blood group and recurrence rates were found (p < 0.05). In case of the patient dependent GCs, a significant association between ovarian cancers and recurrence, fallopian tube cancers and adverse events and survival status, vaginal/vulval cancers and TNM stage and mixed GCs and tumor type (carcinoma) was observed (P < 0.05). Furthermore, multinomial analysis between various confounding factors and GCs revealed that the risk of Cervical, Endometrial and Ovarian cancers to be significant for Type B BG (P < 0.05).ConclusionOur study found that O + BG was the most prevalent among our population. Furthermore, there was a significant association between BG B and endometrial and serous histology in fallopian tube and between BG AB and ovarian malignancies, respectively. Additionally, multinomial analysis revealed higher risk of Cervical, Endometrial and Ovarian cancers for Type B BG (P < 0.05).

Clinical Characteristics of Ear Chondroid Syringoma: A Report of 2 Cases and a Literature Review.

Chondroid syringoma, a mixed tumor of the skin, is an acquired hamartoma that differentiates into hair follicles, sebaceous glands, and apocrine sweat glands. Chondroid syringoma in the ear region is exceptionally rare. However, we present 2 cases of ear chondroid syringoma: 1 involving multiple lesions in the external auditory canal and the other including a single lesion behind the auricle. We reviewed relevant literature to offer insights into the diagnosis and treatment of ear tumors in the future.

Mixed neuroendocrine-non-neuroendocrine neoplasm of the colon treated with laparoscopic resection and adjuvant chemotherapy: a case report.

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the colon is rare with a poor prognosis. Since the first description of a mixed neoplasm 100years ago, the nomenclature has evolved, most recently with the 2022 World Health Organization(WHO) classification system. We describe our experience of a case of locoregionally advanced MiNEN of the descending colon treated with curative laparoscopic resection and adjuvant chemotherapy. The patient is a 72year old woman who presented with haematochezia. Initial clinical diagnosis was poorly differentiated adenocarcinoma of the descending colon, cT2N0M0, cStage I. Laparoscopic partial colectomy of the descending colon with D3 lymph node dissection and intracorporeal overlap anastomosis was performed. The pathological diagnosis however, returned mixed adenocarcinoma-neuroendocrine carcinoma (MANEC) of the descending colon, pT4aN1bM0, pStage IIIB, a subgroup of MiNEN: 70% was neuroendocrine carcinoma (NEC), whilst poorly differentiated mucinous carcinoma constituted 30% of the tumour. She completed 4 courses of irinotecan plus cisplatin (IP) adjuvant chemotherapy and is currently recurrence-free at postoperative year 2. The clinical course of MiNEN depends on the biology of the two components, both of which must be pathologically characterised. Even quantitatively discrete components should be carefully subtyped as their prognostic relevance is undetermined.

A Rare Supraorbital Ridge Mass: The Chondroid Syringoma with Adipocytic Metaplasia

Chondroid syringoma (CS) is a rare benign skin adnexal neoplasm. Its incidence is very low among all primary skin tumors. Diagnosing it clinically can be difficult as it closely resembles other benign salivary or adnexal neoplasms. Until now, only a few cases have been reported from the periorbital region. Clinically, it can be mistaken for epidermal cysts, but ectopic salivary glands are a close differential diagnosis. To diagnose it, a complete removal is usually required, followed by a histopathological examination. We present a unique case of a 45-year-old female patient with a CS in her right supraorbital ridge and review the pertinent literature.

Analysis of ameloblastic fibroma lesion on panoramic radiograph: a case report

Objectives: This case report aims to present a case of ameloblastic fibroma, an odontogenic tumor, and to describe its characteristic radiographic features as observed on a panoramic radiograph. Case Report: A 28-year-old woman presented to the RSGM FKG Unpad with a referral for evaluation of a jaw swelling. According to the patient’s medical history, the swelling had gradually appeared over the past two years. While it was not painful, it caused discomfort, prompting her to seek medical attention. Upon examination, the lesion was found in the posterior region of the mandible, and further diagnostic imaging was recommended to determine the extent and nature of the lesion. Ameloblastic fibroma of the jaw is a benign, relatively rare, mixed odontogenic tumor whose epithelial and mesenchymal components are neoplastic. This tumor is usually diagnosed in the first and second decades of life (72.4%), when odontogenesis has been completed (80% of cases), and mainly affects the mandible. In this case, the lesion was diagnosed in the second decade of life, and occurred in the posterior region of the mandible. Conclusion: Ameloblastic fibroma is a benign odontogenic mixed tumor, although rarely ameloblastic fibroma can recur and develop into malignancy. The aim of this case report is to analyze the radiographic appearance of the lesion with information from the history and clinical signs to establish a correct radiodiagnosis.

Large Pleomorphic Adenoma of the Parotid Gland: Case Report

Pleomorphic adenoma is a benign mixed tumor and the most common neoplasm of the salivary glands. This type of lesion typically presents as slow-growing and asymptomatic. The parotid gland is most frequently affected, accounting for approximately 85% of confirmed cases, although, with lower prevalence, it can also affect minor salivary glands. This report describes a case of pleomorphic adenoma in the superficial lobe of the parotid gland. The case involved a male patient, melanodermic, in his sixth decade of life, with an estimated development of the neoplasm over approximately ten years. Clinical examination revealed a painless swelling in the right parotid region, with a firm lesion upon palpation. Facial computed tomography showed a tumor mass located superficially in the right parotid gland. Surgical excision of the lesion was performed under general anesthesia, and the histopathological examination confirmed the preoperative diagnostic hypothesis of pleomorphic adenoma. After four years of follow-up, there was no recurrence, and the patient remains without esthetic-functional sequelae despite the large size of the lesion.

MALIGNANT COLLISION TUMORS OF THYROID: TWO CASE REPORTS

Collision neoplasm is when two different types of tumors affect the same organ. Collision tumors of the thyroid are extremely rare. This paper describes two cases of patients who had these mixed tumors. The first case is a 59-yearold male patient who presented complaining of mass that was growing for over a year. After a thorough investigation the patient was initially diagnosed with Papillary Thyroid Carcinoma (PTC) and thyroidectomy was performed, however further histologic evaluation of the gland revealed PTC and Medullary Thyroid Carcinoma (MTC). The second case was of a 21-year-old female who presented with a neck swelling for only a month. Radiograph showed two nodules of variable sizes on right and left lobes. After an FNA a diagnosis of PTC was made. The patient later on had a complete thyroidectomy. Histology of the gland revealed PTC in right lobe and Oncocytic carcinoma in left lobe. Since CT tumors are rare, the diagnosis could be challenging. Although, it is of great importance as in some cases the management depends on it. The reported cases here shed the light on the importance of careful and meticulous histological diagnosis, as the accompanied tumors with PTC were both incidentally found.

Mixed neuroendocrine non-neuroendocrine tumors: The quest for evidence

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare mixed tumors containing both neuroendocrine and non-neuroendocrine components that occupy at least 30% of the whole tumor. Biologically, both components appear to derive from an identical cellular precursor undergoing early dual differentiation or late transdifferentiation. While our understanding of MiNENs has improved in recent years, many areas of uncertainty remain. In this context, setting diagnostic criteria capable of capturing the continuum of disease biology while providing clinically meaningful information in terms of prognosis and response to treatments appears vital to advance the field and improve patients’ outcomes. Evidence is needed to generate robust classification schemes, and multi-institutional cooperation will likely play a crucial role in building adequately powered cohorts to address some of the most pressing questions discussed in this Editorial. What is the minimum representation for each component needed to define MiNENs? How can the epidemiology of MiNENs change according to different diagnostic definitions? How can we generate the clinical evidence needed to optimize the management of MiNENs?

Smooth Muscle and Adenoma-Like Renal Tumor (SMART)- A Rare Biphasic Renal Tumor with a Review.

Smooth muscle and adenoma-like renal tumor (SMART) is a biphasic tumor composed of cytologically bland stromal and epithelial components. It has many histopathological mimickers. A 57-year-old man presented with a left renal mass. The left radical nephrectomy showed a 13.5 cm tumor involving the entire kidney. The microscopic examination showed an unencapsulated, well-circumscribed biphasic tumor composed predominantly of intersecting bundles of smooth muscle, admixed with focal epithelial components arranged in cystic, tubular, tubulopapillary, nests, and cords. Both the components lacked nuclear atypia. Using immunohistochemistry, the spindle cells were positive for SMA and desmin, focally positive for CD10, and negative for ER, PR, and HMB45. The epithelial cells were positive for PAX8 and keratin 7 and negative for CD10. We report an additional example of SMART with a literature review. Knowledge about this recently described entity would lead to a better understanding of the clinicopathological features and histogenesis of this tumor.

Immunocytochemistry of myoepithelial cell types in canine mammary tumors

ABSTRACT Myoepithelial cells (MECs) are known to play an active role in mixed mammary tumors and are found in dogs as well as in humans. The study aimed to assess the morphologic features of epithelial and mesenchymal cells and MECs and investigate their roles in epithelial-mesenchymal transformation in different tumor types in canine mammary tumors. Immunohistochemical staining was performed on 165 specimens from benign mixed tumors (BMT), carcinosarcomas, and simple carcinomas (SC). Double immunohistochemical staining was for the antigen pairs p63/actin, p63/vimentin, p63/CK19, p63/CK8, p63/CK14. BMP6 was demonstrated only by single immunostaining. For BMP6, epithelial cells were positive in BMTs, carcinosarcomas, and SCs. Myoepithelial cells were variably positive for p63, actin, vimentin, and CK14. Epithelial cells were usually positive for CK19 and CK8. MECs include both epithelial and mesenchymal components, so metaplasia in epithelial cells can also form in MECs, and these two cell types should be evaluated together.

Versican Proteolysis by ADAMTS: Understanding Versikine Expression in Canine Spontaneous Mammary Carcinomas.

Background: The present study investigates VKINE, a bioactive proteolytic fragment of the proteoglycan VCAN, as a novel and significant element in the tumor extracellular matrix (ECM). Although VKINE has been recognized for its immunomodulatory potential in certain tumor types, its impact on ECM degradation and prognostic implications remains poorly understood. Objectives: This study aimed to evaluate VCAN proteolysis and its association with ADAMTS enzymes involved in extracellular matrix remodeling in spontaneous canine mammary gland cancer. Methods: The expression levels of VKINE, ADAMTS enzymes, and collagen fibers were comparatively analyzed in situ and in invasive areas of carcinoma in mixed tumor (CMT) and carcinosarcoma (CSS) with different prognoses. Results: VKINE was notably expressed in the stroma adjacent to the invasion areas in CMT, whereas ADAMTS-15 was identified as the enzyme associated with VCAN proteolysis. Inverse correlations were observed between type III collagen and VCAN expression in in situ areas. Conclusions: Our findings suggest that VKINE and ADAMTS-15 play crucial roles in the tumor microenvironment, influencing invasiveness and type III collagen deposition. This study contributes to a better understanding of the dynamics within the ECM, paving the way for potential new tools in diagnosing and treating human and canine mammary tumors.

Mixed Pancreatobiliary Ductal Adenocarcinoma and Squamous Cell Carcinoma Arising from an Ectopic Pancreas in a Gastric Duplication Cyst-A Rare Double Diagnosis.

Gastric duplication cysts (GDCs) are rare congenital anomalies, often identified during infancy or childhood. Although typically benign, there have been sporadic reports of malignant transformations, including adenocarcinoma and rare mixed tumors. Herein, we describe a rare case of mixed pancreatobiliary ductal adenocarcinoma and squamous cell carcinoma occurring within a GDC in a 54-year-old Korean woman with a history of melena and hematemesis. Initial gastroscopy and positron emission tomography-computed tomography (PET-CT) revealed a protruding stomach mass. A laparoscopic total gastrectomy was performed, and histological examination confirmed a mixed carcinoma originating from an ectopic pancreas within the duplication cyst. This case is unique as it is the first reported instance in the world of mixed pancreatobiliary ductal adenocarcinoma and squamous cell carcinoma arising from an ectopic pancreas within a GDC. This highlights the importance of considering pancreatobiliary-type adenocarcinoma in the differential diagnosis of malignancies originating from GDCs, which has implications for treatment strategies.

External auditory canal chondroid syringoma with bone erosion: A CARE case report

IntroductionChondroid syringoma or ceruminous pleomorphic adenoma is a benign mixed cutaneous tumor. It is the second most frequent glandular lesion in the external auditory canal, but no cases associated with bone erosion were found in a PubMed search. Case reportThe present CARE case report details a chondroid syringoma in the external auditory canal with associated bone lysis, and its management. DiscussionChondroid syringoma is a differential diagnosis for other external auditory canal tumors. Forms causing bone erosion are rare, but should not challenge the diagnosis. Current treatment consists in complete and broad surgical resection and prolonged follow-up due to the risk of recurrence and of malignant transformation.

The Outcomes of Onco-Testis Sperm Extractionat the Time of Radical Orchiectomy.

To evaluate outcomes of onco-testis sperm extraction (TESE) and to define potential predictors of successful surgical sperm retrieval (SSR). For this study, we examined all men (i) diagnosed with a testicular mass, (ii) who had azoospermia, and (iii) who underwent a radical orchiectomy and onco-TESE. Our institutional database of testicular cancer (TCA) patients was reviewed. Demographics, baseline endocrine and oncological characteristics, and treatments received were recorded. The onco-TESE Technique was performed at the time of radical orchiectomy before the specimen was sent for formal histopathological assessment. Onco-TESE was considered successful if viable sperm was found. Logistic regression assessments were performed to evaluate predictors of successful onco-TESE. Thirty-eight men with a median age of 35 were included in the analysis. Median baseline total testosterone, LH, and FSH levels were 419ng/dL, 10.9mU/mL, and 27mU/mL, respectively. The median pre-TESE testicular volume was 11mL. Of men who underwent radical orchiectomy, 58% had unilateral tumors at the time of the procedure. 42% had bilateral tumors, which were synchronous in 25%, and asynchronous tumors in 75%. Pathologically, 76% had germ cell tumor (83% had pure seminoma, and 17% had mixed germ cell tumor). At onco-TESE, 24% of the patients had successful SSR. No variables had a statistically significant association with successful SSR. Onco-TESE represents a useful option for testis cancer patients who wish for future paternity, with a quarter of such patients having sperm found.