Medullary Adenocarcinoma Research Articles

Characterizing POLE Mutation-Associated Colorectal Carcinoma: Clinical and Pathologic Insight

Abstract Introduction/Objective Colorectal carcinoma (CRC) is one of the most common cancers and a leading cause of cancer-related death in the United States. Pathogenically, colorectal carcinoma is a heterogeneous disease that develops via stepwise accumulation of well-characterized genetic and epigenetic alteration. Identification of DNA polymerase mutation leads to the characterization of a new molecular pathway of carcinogenesis named the POLE pathway. Methods/Case Report Utilizing the cBioportal platform and Cancer Genome Atlas (TCGA) Firehouse Legacy data, we identified 118 cases of CRC with mutations in the POLE gene. We evaluated the various clinical and pathologic features of POLE mutation-associated CRC. Results (if a Case Study enter NA) Within the cohort of 118 cases linked to mutations in the POLE gene, gender distribution reveals that 63 individuals, comprising 53.8% of the sample, are male, while 42 individuals, accounting for 35.9%, are female. Ethnicity breakdown showcases a predominantly White population, with 92 cases (78.6%), followed by 8 cases (6.8%) attributed to Asian-Far East/Indian Subcontinent descent, 5 cases (4.3%) categorized as Asian, and 4 cases (3.4%) each identified as Black and Black or African American. Additionally, one case (0.9%) has an unknown ethnicity, while 4 cases (3.4%) have unspecified racial backgrounds. The average age at diagnosis is recorded at 48.5 years, with ages ranging from 25 to 85, signifying a broad age spectrum within the affected population. Delving into cancer subtypes, the majority of cases, constituting 64 instances (54.2%), manifest as colon adenocarcinoma, while 38 cases (32.2%) present as rectal adenocarcinoma. Moreover, 9 cases (7.6%) are characterized as colorectal adenocarcinoma, 6 cases (5.1%) are classified as mucinous adenocarcinoma of the colon and rectum, and one case (0.8%) manifests as medullary adenocarcinoma of the colon. This detailed elucidation provides a comprehensive understanding of the demographics and clinical presentation within the cohort affected by POLE gene mutations. Conclusion In summary, our research has meticulously examined 118 instances of colorectal carcinoma (CRC) intricately linked to mutations in the POLE gene. Within this cohort, a predominant demographic emerges, with a notable prevalence among individuals of White ethnicity. Delving deeper into the pathological spectrum, colon adenocarcinoma emerges as the prevailing subtype, exemplifying the intricate interplay between genetic aberrations and cancer manifestation.

Primary medullary adenocarcinoma of the colon: Literature review and case series

AimsMedullary carcinoma of the colon is a rare subtype of adenocarcinoma, first described in 1999. Clinically known to have a favourable prognosis in comparison to poorly differentiated cancers, it is associated with deficient mismatch repair. This is an observational single center study of patients with medullary cancer, and comparison with the current literature. MethodsWe performed a search of the pathological database at our institution for medullary adenocarcinomas between the years of 2016–2023 and reviewed their clinical information to collect all relevant data including patient history, hospital admissions. surgery and clinic visits. We then performed a literature search using Pubmed for search terms medullary cancer/carcinoma of the colon/colorectum. Results11 patients were found in our database, 34 studies in the literature, 19 retrospective cohort studies (3144 patients) and 13 case reports. 81.8% (vs. 73.22% in cohort studies) were female patients. 8/11 patients' tumours had lympho-vascular invasion with 2/11 perineural involvement. Immunohistochemistry demonstrated 11/11 patients’ tumours with MLH1 and PMS2 loss, and presence of MSH2 and MSH6. Cohort studies demonstrated 302/1897 (15.92%) tumours had perineural invasion with 1133/2151 (52.67%) demonstrating lympho-vascular invasion. MLH1 testing was available for 192 patients, with 93.75% having loss of MLH1. ConclusionOur cohort of medullary cancer patients were similar to that in the literature, with regards to demographics, staging and tumour characteristics. A longer follow-up time is required for our cohort to analyze long term survival outcomes.

Primary medullary adenocarcinoma of the colon: Literature review and case series

Aims: Medullary carcinoma of the colon is a rare subtype of adenocarcinoma, first described in 1999. Clinically known to have a favorably prognosis in comparison to poorly differentiated cancers, it is invariably associated with mismatch gene repair. This is an observational study of Hobart’s patient population with medullary cancer, and compares data with the current literature. Methods: We performed a search of the pathological database at our institution for medullary adenocarcinomas between the years of 2016 and 2023 and reviewed their clinical information to collect all relevant data including patient history, hospital admissions, surgery and clinic visits. We then performed a literature search using PubMed for search terms medullary cancer/carcinoma of the colon/colorectum. Results: Eleven patients were found in our database, 34 papers in the literature (19 retrospective cohort studies and 13 case reports). 81.8% (vs. 73.22% in cohort studies) were females. 8/11 patients had lymphovascular invasion (LVI) with 2/11 patients had perineural involvement (PNI). The immunohistochemistry (IHC) results showed that in all (11/11) patients’ tumors, there was a loss of MLH1 and PMS2 proteins, while MSH2 and MSH6 proteins were present. Cohort studies demonstrated 302/1897 (15.92%) patients had perineural invasion (PNI) with 1133/2151 (52.67%) demonstrating LVI. MLH1 testing was available for 192 patients, with 93.75% having loss of MLH1. Conclusion: Our cohort of medullary cancer patients was similar to that in the literature, with regard to demographic, staging, and tumor characteristics. A longer follow-up time is required for our cohort to produce comparable survival outcomes.

Sidedness determines clinical characteristics and survival outcomes in medullary adenocarcinoma of the colon

Colon medullary adenocarcinoma (MAC) is a rare histologic subtype. Clinical presentation and cancer outcomes of MAC, compared to colon adenocarcinoma (AC), remain incompletely described. Annual age-adjusted incidence rates were computed using Surveillance, Epidemiology, and End Results (2002–2017). A cohort analysis using the National Cancer Database (2010–2016) compared patient characteristics in an unmatched dataset and prognostic characteristics in a 1:1 matched subset. Reported annual age-adjusted incidence of MAC has significantly increased, with an average annual percent change (APC) increase of 23.8% (95% CI: 19.2–28.6); concurrent AC incidence declined (APC: − 2.8, 95% CI: − 3.1 to − 2.8). Analyses of 1018 MAC and 210,784 AC unmatched patients showed that MAC patients were more often older, female, and white, with higher disease stage, poorly-differentiated tumors, right-sided laterality, and lymphovascular invasion (all p < 0.0001). Among those with known microsatellite status, instability was more prevalent among MAC than AC patients (82% vs. 24%, p < 0.0001). Multivariate analyses of the matched dataset revealed that MAC histology was not independently associated with overall survival. However, when stratifying by laterality, left-sided MAC was associated with shorter survival when compared to right-sided MAC (HR 1.66, 95% CI 1.16–2.38) and right-sided AC (HR 1.54, 95% CI 1.12–2.12). The reported incidence of MAC is increasing, in contrast to the declining incidence of AC. MAC clinical and molecular features are distinct from AC and likely account for outcome differences. Overall, left-sided MAC was associated with the shortest OS. Molecular profiling may improve treatment guidelines for MAC.

Survival pattern of rare histological types of breast cancer in a Nigerian institution.

Introductionbreast cancer is the most common cancer affecting women worldwide. It is a heterogeneous disease with diverse histological types that are associated with different natural history and response to therapy. Invasive ductal and lobular carcinoma are the most common histological types. There are rare histological types with different biological behaviours from the common types, although treatment approaches are the same. Data on rare histological types of breast cancer in our population are scarce raising the need to identify these patients and document their treatment outcome. The objectives of this study are to determine the proportion and treatment outcomes of breast cancer patients with rare histological types.Methodsthis was an observational retrospective study using records of patients treated for breast cancer at the University College Hospital Ibadan Nigeria from 2008 to 2012. Patients with rare histological types were selected for further analysis. Data on patient and tumour characteristics were extracted and five-year survival pattern was determined using Kaplan Meier method.Resultsthe total number of patients with breast cancer was 761. Thirty-two (4.2%) had rare histology that consisted of medullary carcinoma 14(1.9%), mucinous carcinoma 10(1.4%) and 2(0.3%) each for squamous cell carcinoma, stromal sarcoma, cribriform carcinoma and Paget's disease. The overall five-year survival was 50% with median survival of 52 months.Conclusionthe proportion of breast cancer patients with rare histology is low similar to other reports among Caucasians. Medullary adenocarcinoma was the most common subtype followed by mucinous adenocarcinoma.

Metastatic Medullary Adenocarcinoma to the Liver: 32 Years after Clinical Remission

Metastatic Medullary Adenocarcinoma to the Liver: 32 Years after Clinical Remission

Medullary Adenocarcinoma of Colon: Distinct Entity with a Favorable Prognosis

Medullary Adenocarcinoma of Colon: Distinct Entity with a Favorable Prognosis

Alpha-fetoprotein-producing adenocarcinoma in which the metastatic route was determined from calcified lesions.

Alpha-fetoprotein (AFP)-producing adenocarcinoma is known for its rapid progression and poor prognosis, and chemotherapy regimens are yet to be standardized. Here we describe the first report of AFP-producing adenocarcinoma with calcification. The metastatic route was visualized from the calcification, and combination chemotherapy was performed. A 77-year-old Japanese man was transferred to our hospital for treatment of liver tumors. Computed tomography (CT) revealed multiple liver tumors with portal vein tumor thrombosis. The tumors were highly attenuated before enhancement, suggesting various degrees of calcification. Serum levels of carcinoembryonic antigen (CEA), AFP, and the proportion of fucosylated AFP were considerably elevated. Gastroduodenoscopy revealed an elevated tumor occupying the duodenal bulb with an ulcerative lesion in the vicinity of the gastroduodenal junction, and biopsy specimens from the duodenum and liver revealed medullary adenocarcinoma with calcification. Three-dimensional reconstruction of CT images clearly showed that the calcified lesions had spread from the gastroduodenal junction to the liver via a route comprising the corresponding local vein, the superior mesenteric vein, and portal vein. The patient was accordingly diagnosed with calcified AFP-producing adenocarcinoma with multiple liver metastases. Combination chemotherapy using TS-1 and cisplatin (CDDP) resulted in a striking response for the initial 4months in terms of tumor markers and CT findings. This is the first report of AFP-producing adenocarcinoma with calcification. A metastatic route from the primary tumor to the liver was clearly visualized by tracing the calcified lesions. Combination chemotherapy based on 5-fluorouracil and CDDP may have the potential to prolong survival.

Pathologic quiz case: a 79-year-old woman with a black, ulcerated cecal tumor and 3 negative guaiac test results. Medullary adenocarcinoma of the colon, poorly differentiated.

Pathologic quiz case: a 79-year-old woman with a black, ulcerated cecal tumor and 3 negative guaiac test results. Medullary adenocarcinoma of the colon, poorly differentiated.

The indications and clinical curative effects of modified neck dissection in head and neck cancers

OBJECTIVE Functional neck dissection was first described by Bocca and Pignataro in 1967. It has been used in clinical practice for years, but remains controversial among neck-surgery experts. This study was designed to evaluate indications and curative effects of functional-neck dissection (FND). METHODS One hundred and fifty-two cases which underwent FND were reviewed with an analysis of pathological specimens and follow-up datas. RESULTS The series of FND included 20 cases of tongue carcinoma, 23 cases of larynx carcinoma, 96 cases of thyroid papillary adenocarcinoma, 9 cases of foilicular adenocarcinoma and 4 cases of medullary adenocarcinoma; the five-year recurrence rate for tongue carcinoma was12.5%, 14.3%, 400% and for a larynx carcinoma was 20.0%, 16.7%, 50.0% in No stage, N, stage, N2~ stage, respectively. The 5-year recurrence rate of thyroid papillary adenocarcinoma was 6.5%, 7.1% in Nla, Nlb, respectively. CONCLUSION Functional neck dissection is indicated in early and low malignant head and neck neoplasms and results in satisfactory curative effects.

Long‐Term Ethanol Consumption in ICR Mice Causes Mammary Tumor in Females and Liver Fibrosis in Males

Although epidemiological studies indicate that ethanol consumption and the risk of breast cancer are positively associated in women, experimental animal models have not yet been developed that provide evidence to support this relationship. To clarify alcohol-related liver injury, it is important to reproduce, in laboratory small animals, the liver fibrosis observed in human alcoholics. However, in mice the induction of fibrosis has failed. The present study describes the first experimental models to produce mammary tumors in female ICR mice and liver fibrosis in male ICR mice treated long-term with ethanol. The study consisted of two parts. To induce mammary tumors, female ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 25 months, with solid diet supplied ad libitum. To induce liver fibrosis, male ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 10 to 15 months. Control female and male mice were given tap water. In 9 (45%) of 20 ethanol-treated female mice, mammary tumors occurred at 8 to 24 months after ethanol intake began, whereas spontaneous mammary tumor was not found in the 20 control female mice. The tumors were composed histopathologically of either papillary adenocarcinoma or medullary adenocarcinoma of glandular epithelial origin. In the ethanol-treated male mice, early hepatic fibrosis at the centrilobular and pericellular areas and central-central bridging were observed at the 10th month, and marked fibrosis at the centrilobular, pericellular, and periportal areas and bridging between the neighboring vascular tissues were observed at the 15th month, which suggested that the initial fibrosis arose from the centrilobular area. No abnormalities other than mild fatty infiltration were found in livers of the control male mice. These murine models may be useful to study the role of ethanol in mammary tumorigenesis and the pathogenetic mechanisms of ethanol liver injury.

Medullary adenocarcinoma of the colon: Clinicopathologic study of 11 cases

Colonic carcinomas with minimal or no glandular differentiation are a heterogeneous group of neoplasms which differ in their histologic appearance, clinical features, prognosis and molecular characteristics. Since 1990, we prospectively identified 11 patients with a predominantly solid (nonglandular) adenocarcinoma of the colon for which the term medullary adenocarcinoma of the colon (MAC) is proposed. The clinical, histological, histochemical, and immunohistochemical features of these neoplasms were studied. All patients with MAC were women with tumors in the cecum or proximal colon. Histological analysis showed nests or trabeculae of regular small to medium-sized cells with moderate amounts of eosinophilic cytoplasm; some cells contained mucin vacuoles. The nuclei had an open chromatin pattern and exhibited prominent nucleoli. Lymphatic permeation was present in most cases. Immunohistochemical reactions were positive for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen. Despite its histological resemblance with endocrine tumors, MAC is negative for endocrine markers. Of the eight patients for whom follow-up is available, four patients (two Dukes B and two Dukes C) are alive and well 1 to 4 years after surgery, one patient (Dukes C) died of tumor, one patient is alive with liver metastasis 4 years after surgery, and two patients died in the postoperative period. MAC appears to be a distinctive clinicopathologic entity. This tumor should be distinguished from other more aggressive, nonglandular tumors of the colon.

Early gastric cancer manifested as brain metastasis: Report of a case

A case of early gastric cancer, limited to submucosal layer, which was manifested as cerebral metastasis is presented herein. A 47-year-old man was admitted to Nagaoka Chuo General Hospital with convulsions and a disturbance in consciousness, where a computed tomography (CT) scan revealed a cerebral tumor in the left temporal lobe. The resected tumor was identified as a metastatic adenocarcinoma. Further investigation revealed gastric cancer involving the posterior wall of the cardia. At laparotomy, multiple and small metastases of the liver and a jejunal metastasis were found and a palliative total gastrectomy was performed. The surgical specimen revealed a protruding, poorly differentiated medullary adenocarcinoma, with invasion of the submucosal layer. The patient died 4 months after undergoing the laparotomy. This case report is presented to make clinicians aware of the possibility that early gastric cancers may present as brain metastasis.

Breast Metastases of Prostatic Carcinoma: Immunohistochemical Case Study

A breast mass developed in a patient receiving estrogen therapy for prostatic cancer. The prostate tumor was adenocarcinoma of small acinar type, whereas that of the breast was infiltrating medullary adenocarcinoma. Histological features of the two tumors differed and double cancer was suspected by conventional pathological study. However, immunohistochemical staining with prostatic specific antigen and prostatic acid phosphatase was positive in each tumor. These results indicate the breast tumor to be a metastasis from the prostatic cancer.

A CASE REPORT OF SO-CALLED CARCINOSARCOMA OF THE BREAST

A rare malignant neoplasm, “so-called carcinosarcoma” of the breast was experienced in out clinic. The patient was a 41-year-old female with a right giant breast tumor. The tumor was 18×19cm in size and occupied almost all the quadrants of the right breast with skin ulceration. A right radical mastectomy was performed Histological examination revealed the mixture of medullary adenocarcinoma and “sarcoma-like” appearance. In some areas, transitional changes from medullary adenocarcinoma to “sarcoma-like” appearance were found. The “sarcoma-like” appearance was composed of spindle-shaped cells, in which tight junction and tonofilaments were appreciated electron-microscopically. Therefore, these findings led to the conclusion that “sarcoma-like” appearance was spindle cell carcinoma and the whole tumor was “so-called carcinosarcoma”. The patient died of cachexia 9 months postoperatively.

High incidence of rat mammary carcinoma by oral administration of ethyl methanesulphonate

Ethyl methanesulphonate (EMS), one of the alkylating agents, is known to be a potent mutagen. We tested EMS for its carcinogenicity in female rats by oral administration. EMS was dissolved in drinking tap water at a concentration of 10(-3) M and was given for the first 12 weeks. The subcutaneous tumors were noticed as early as 16 weeks after initiating the experiment. At the 32nd week, all the surviving rats produced tumors; the majority were multiple tumors in the neck, axillar and inguinal areas corresponding to bilateral mammary glands. Histologically, the prevailing feature of the tumors was infiltrating medullary adenocarcinoma consistent with carcinoma of mammary duct origin. Neither regional lymph node involvement nor distant metastases were shown, but intraductal spread of carcinoma was a marked finding during the 32-week period.