Medullary Carcinoma Patients Research Articles

Divergent Metastatic Patterns Between Subtypes of Thyroid Carcinoma Results From the Nationwide Dutch Pathology Registry.

BackgroundMetastatic disease is the main cause of cancer-related mortality in thyroid carcinoma (TC) patients. Clinical studies have suggested differences in metastatic patterns between the different subtypes of TC. This study systematically evaluates the metastatic patterns of different subtypes in TC patients.MethodsA nationwide review of pathological records of all 650 patients diagnosed with a primary malignancy in the thyroid who underwent an autopsy between 1991 and 2010 was performed. Patients were selected from the Dutch pathology registry (PALGA).ResultsMetastatic disease was present in 228 (35.1%) patients and was found in 38.7%, 17.3%, 75.4%, and 47.8% of patients with follicular, papillary, anaplastic, and medullary types of TC, respectively (P < .0001). The majority of patients had more than 1 metastasis. The most common site of metastatic disease was the lung for papillary (79.7%), follicular (72.9%), and anaplastic (92.1%) carcinoma but not for medullary carcinoma (56.3%), P < .0001. Medullary carcinoma patients most frequently had metastases to the liver (81.3%). The combination of metastases also differed between subtypes.ConclusionThere are major differences in metastatic patterns between different subtypes of TC. The patterns and frequencies identified in this autopsy study may reflect the underlying biology of metastatic thyroid cancer and have potential to influence future monitoring and treatment strategies depending on clinical correlations.

Clinicopathological importance of colorectal medullary carcinoma

Medullary carcinoma (MC) is a rare tumor with a solid growth pattern without glandular differentiation and constitutes less than 1% of colorectal cancers. Lymph node positivity and distant organ metastasis were reported to be lower than in other poorly differentiated adenocarcinomas. Therefore, the diagnosis of MC is pathologically important in terms of follow-up and treatment. We aimed to investigate the characteristics of medullary cancer in our case series. 427 patients with colorectal cancer (CRC) who underwent surgery between January 2011 and December 2017 were evaluated retrospectively in 2 groups as MC (n = 13) and non-MC (n = 414) in terms of demographic characteristics, pathological data, and oncological outcomes. 76.9% (n = 10) of the MC group were female while 36% (n = 149) of the non-MC group were female (p = 0.003). The tumors were located in the right colon in 84.6% (n = 11) of the MC patients and in 26.6% (n = 110) of the non-MC patients (p < 0.001). The rate of laparoscopy was 83.8% for all CRC patients, and 53.8% for the MC group (p = 0.01). T4 cases (69.2%) and tumor volume (131 ± 87 cm3) in the MC group were significantly higher than in the non-MC group (p < 0.05). The rate of high microsatellite instability (MSI) was 85%. 5‑year overall survival was 75% for the patients with MC and 82% for non-MC (p = 0.13). MC is commonly localized in the right colon, has a large tumor size, and is mostly diagnosed in the T4 stage. As MC most likely have defects in DNA MMR, correct pathological diagnosis is important for postoperative treatment and the prognosis of the patients.

Comparison of Survival Outcomes in Medullary Carcinoma and Invasive Ductal Carcinoma of the Breast

Aim: To compare clinicopathological characteristics and prognoses of medullary carcinoma (MC) and invasive ductal carcinoma (IDC) of the breast. Patients &amp; methods: We screened patients from the SEER database. Kaplan–Meier analysis and Cox proportional hazards models were used to investigate influence on survival. Propensity score matching analysis was performed to reduce possible bias. Results: Compared with IDC, MC tended to be younger patients, poor differentiation, negative estrogen receptor and progesterone receptor and chemotherapy. Better overall survival and disease-specific survival were observed in MC patients than in IDC patients. It shared several prognostic factors. Worse disease-specific survival was observed in IDC patients than in MC patients (HR: 1.590; 95% CI: 1.475–1.714; p &lt; 0.001). Conclusion: The clinical features and outcomes had evident differences between MC and IDC patients. These findings will provide more information for the prognosis of MC and IDC.

Tumor cells may circulate in medullary thyroid cancer patients independently of serum calcitonin.

Early detection of tumor relapse is a major issue in patients with medullary thyroid carcinoma. Calcitonin has been reported as a sensitive and accurate marker for recurrence of medullary thyroid carcinoma after thyroidectomy. Recent evidence nevertheless reveals pitfalls in calcitonin immunoassays due to the presence of heterophilic antibodies or macroaggregates. Calcitonin can also remain undetectable despite metastasis of rare tumor cells in thyroidectomized patients. In this context, we designed a sensitive and specific technique to identify calcitonin-positive circulating tumor cells (CTC) in medullary thyroid carcinoma. We demonstrate that calcitonin-positive CTCs are present in the peripheral blood of medullary carcinoma patients following complete thyroidectomy. Unexpectedly, the presence of CTCs could be identified up to 12 years after surgery even in the absence of detectable levels of serum calcitonin.

Genotype-phenotype correlations in multiple endocrine neoplasia type 2

To evaluate the relationship between different RET mutations and the aggressiveness of hereditary medullary thyroid cancer (HMTC) or the presentation of other endocrine disorders in patients with multiple endocrine neoplasia type 2 (MEN2). A total of 73 thyroid medullary carcinoma patients from 22 Chinese kindreds who were treated in our center from 2010 to 2015 were enrolled. RET genes in the patients and their relatives were screened. According to the clinical data and 2015 American Thyroid Association (ATA) guidelines, patients were classified into 3 RET mutation risk groups: Modest, 24 cases; High, 48 cases; and Highest, 1 case. Multivariate analysis showed an increased likelihood of MTC stage III or IV at diagnosis with increasing of age and risk. The likelihood increased 11.6% per year of age at surgery (95% confidence interval, 1.040-1.198; P=0.002). The likelihood in patients with high risk was 7.9 times higher than patients with modest risk (95% confidence interval, 1.607-38.717; P=0.003). Aside from one patient with MEN2B, other 72 patients were MEN2A, of them, 28 cases from 7 kindreds with classical MEN2A (codon 634 & 618), 14 cases from 3 kindreds with cutaneous lichen amyloidosis (codon 634), 4 cases from 1 kindred with Hirschsprung's disease (codon 620), and 26 cases from 10 kindreds with familial MTC. The aggressiveness of HMTC and the presentation of other endocrine diseases are related to specific RET mutations. For RET mutation carriers, MTC and other endocrine diseases should be diagnosed and treated early based on the RET genotypes.

Medullary carcinoma in the colorectum: a systematic review and meta-analysis

Medullary carcinoma (MC) is a very rare variant of colorectal carcinoma (CRC). Its clinicopathologic findings are not fully elucidated. The aim of this study was to investigate the clinicopathological characteristics of MC in the colorectum through a systematic review and meta-analysis. The meta-analysis examined the incidence, age, sex, site, mismatch repair deficiency (MMRd), MMR protein expression, ARID1A expression, BRAF(V600E) mutation, KRAS mutation, and survival rate of MC. The 21469 CRCs included 462 MCs in 16 eligible studies, representing an estimated incidence of MC of 0.027 (95% confidence interval [CI] 26 0.016-0.045). MC frequently occurred in female patients and in the right colon. Lymph node metastasis of MC was significantly lower than that of poorly differentiated adenocarcinoma/undifferentiated adenocarcinoma (PDA/UDA). In addition, MC had a higher MMRd rate (0.892, 95% CI 0.758-0.956), higher BRAF(V600E) mutation rate (0.652, 95% CI 0.143-0.954) and lower KRAS mutation rate (0.171, 95% CI 0.065-0.378) than PDA/UDA and conventional adenocarcinoma. Patients with MC had significantly better overall survival rate compared to patients with PDA/UDA (hazard ratio 0.441, 95% CI 0.262-0.742). However, there was no significant difference of overall survival rate between MC and conventional adenocarcinoma patients. MC predominantly occurred in females and in the right colon, and had different molecular characteristics and behaviors compared to PDA/UDA and conventional adenocarcinoma.

Clinical Analysis of Medullary Carcinoma of the Breast

Purpose: Medullary carcinoma of the breast is a variant of breast cancer characterized by the histologic appearance of poorly differentiated cells surrounded by a prominent lymphoid stroma. Medullary carcinoma has been reported to carry a prognosis better than other invasive breast carcinomas, but it is frequently overdiagnosed due to the difficulty in diagnosis. The aim of this study was to assess the clinical manifestations and outcome of medullary carcinoma of the breast. Methods: We reviewed the data of 91 patients diagnosed with medullary carcinoma and 3,743 patients with invasive ductal carcinoma, not otherwise specified (NOS) from January 1980 to December 2005 at Yonsei University Severance Hospital. The clinicopathologic features, disease free survival (DFS) and overall survival (OS) for patients with medullary carcinoma were compared with those of the NOS patients. Results: With reviewing the pathologic slides, 69 (75.8%) patients had findings compatible with typical medullary carcinoma (TMC) and the remaining 22 (24.2%) patients were reclassified as atypical medullary carcinoma (AMC). Early stage cancer was more frequent at medullary carcinoma and lymph node positive cancer was less frequent at medullary carcinoma. The expression of ER/PR was positive in either the TMC (18.9%/16.2%) and AMC (15.0%/20.0%) as compared to the NOS (63.2%/57.2%), and the difference was significant (p<0.001). In contrast, the HER-2/neu expression rate was significantly higher in the TMC (47.4%) and AMC (45.5%) than in the NOS (28.3%, p=0.001). The 10year disease free survival and 10-year overall survival of the atypical medullary carcinoma patients (67.8%, 77.8%) were in fact similar to the NOS carcinoma patients (68.3%, 74.7%). There was significant difference in 10-year disease free survival and 10-year overall survival between the TMC (77.8%, 86.0%) and NOS carcinoma (68.3%, 74.7%) patients (p=0.002, p=0.006). Conclusion: The clinical outcome of typical medullary carcinoma is favorable in spite of its aggressive pathologic features and it differs from atypical medullary carcinoma. For precise prediction of prognosis of medullary cancer, we should apply strict criteria for the diagnosis of subtype with medullary features.

Multinodular goiter: surgical management and histopathological findings.

The purpose of this study was to assess histopathological findings after a bilateral near-total thyroidectomy (residual thyroid tissue about 4 to 5 g) for multinodular goiter (MNG). The 270 patients included 238 women and 32 men with a mean age of 52 years (range: 19-82 years) who had MNG involving the entire gland and had undergone a primary bilateral surgical procedure between 1993-1998. There was no intra- or postoperative mortality. Indications for the MNG surgery were suspected malignancy (7.7%), thyrotoxicosis (27.7%), pressure on cervical structures with tracheal deviation (38%), significant cosmetic deformity in young female patients (6.6%) and intrathoracic extension of the MNG (19.6%). Grave's disease was not included in our study. The surgical specimen weight ranged from 60 to 560 g (average 120 g). Final pathological findings were benign in 237 patients (87.8%) and malignant in 33 patients (12.2%). Nineteen patients were diagnosed with macroscopic (ten patients) or microscopic (nine patients) types of papillary carcinoma: there were two patients with the follicular variant of papillary carcinoma, three with lymphoma and Hashimoto's thyroiditis, three with medullar carcinoma, three with anaplastic carcinoma, two with follicular carcinoma and one with Hurthle cell carcinoma. A true total completion thyroidectomy was performed only for the medullary carcinoma patients and for four of the "high-risk" papillary carcinoma patients. Permanent (>12 months) unilateral recurrent paralysis occurred in four patients (1.4%), permanent (>12 months) hypoparathyroidism in ten patients (3.7%) and hypertrophic or keloid scar in 14 patients (5.1%). Our results suggest that near total thyroidectomy with minimal residual tissue is a versatile surgical procedure for various histopathological features in MNG patients. Low rates of postoperative complications were observed.

Identification and characterization of calcitonin forms in plasma and urine of normal subjects and medullary carcinoma patients.

Different immunoreactive calcitonin (CT) forms were identified by a reversed phase high performance liquid chromatography gradient system in plasma and urine of normal subjects. The separated CT components were characterized by chemical and enzymatic methods and found to be identical in normal subjects and medullary thyroid carcinoma patients. Of seven major CT forms we identified monomeric human CT-(1-32), its sulfoxide form, and dimeric CT in plasma. The monomeric, but not the dimeric form, was also detected in urine. A predominant CT component in plasma with a molecular weight of about 12,000 may correspond to a biosynthetic precursor of the hormone.

A flow cytometric DNA analysis of medullary thyroid carcinoma.

Flow cytometric DNA analysis of biopsy specimens from 10 patients with medullary carcinoma of the thyroid (MCT) was performed to evaluate the possible value of such data as indicators of the biologic behavior of these tumors. Some of the tumors had a unimodal distribution of nuclear DNA content, whereas others were bimodal. The mean modal DNA content in the cells of unimodal medullary carcinomas was not higher than that in the cells of thyroid parenchyma with a normal histologic appearance. This finding contradicts previous reports based on conventional cytophotometry. Bimodal DNA histograms were found in biopsy specimens from four patients, and the two patients with predominantly spindle-shaped cells belonged to this group. The total of nine biopsy specimens with bimodal DNA distributions were all from metastatic foci. Bimodal patterns were found, however, to co-exist with unimodal patterns, when several samples were examined from the same case. Bimodality or more severe aneuploidy did not seem to be related to shorter survival of the patients. The mean value of the percentage of cells in S-phase in our MCT series was higher than in follicular but lower than in anaplastic carcinomas. This fits well with clinical studies, where medullary carcinoma patients have been found to live longer than patients with follicular carcinomas but for a shorter time than those having anaplastic carcinomas.

Epidemiology of breast carcinoma IV: age and histologic tumor type.

The purpose of this study was to correlate major chronologic events known to have a bearing on the risk for developing breast carcinoma with histologic tumor type. Data were obtained for 1024 consecutively treated patients with the seven most common forms of mammary carcinoma. The age of occurrence of the following events was determined: menarche; first marriage; first pregnancy and first childbirth; last pregnancy and last childhood; diagnosis. The interval between each of these events and diagnosis of breast cancer was also calculated. Patients with medullary carcinoma had a significantly lower mean age at diagnosis than those with any of the other tumor types. Because of the lower mean age at diagnosis, medullary carcinoma patients were found to have significantly shorter intervals between age at diagnosis and the following: menarche, first pregnancy or first childbirth, and last pregnancy or last childbirth. Intervals between age at diagnosis and these other events were not significantly different among patients with other types of carcinoma. The ages of menarche, marriage, or pregnancy were not related independently to any tumor type. These data indicate that except for current age, the age of occurrence of major risk factors for developing breast cancer is unrelated to the histological type of tumor a patient develops.