Clinicopathological Profile of Medullary Thyroid Carcinoma-Could We Predict Aggressive Behavior?

Medullary thyroid carcinoma (MTC) accounts for only 2-5% of all thyroid malignancies. Clinical and pathological characteristics alone may suffice to predict outcomes, but unstable behavior in some cases suggests that other factors may influence a worse course of the disease. This study aims to identify criteria that could predict increased aggressiveness. We analyzed 59 consecutive MTC cases. We focused on the relationships among clinicopathological characteristics, parameters of aggressiveness (extrathyroidal extension, lymphovascular invasion, and lymph node metastasis), and parameters for MTC grading. Statistically significant correlations were found for tumor size, lymphovascular invasion, and lymph node metastasis and tumor focality and lymph node metastasis. Our results showed, in tumors larger than 40 mm, odds ratios (ODs) of 13.695 and 6 for lymphovascular invasion and lymph node metastasis, respectively; in multifocal tumors, we registered an OD of 9.42 for lymph node metastasis. No significant correlation was found for the parameters of the MTC grading system when assessed individually and integrated by reporting low-grade and high-grade risk groups. Although our data indicate that lymphovascular invasion and lymph node metastasis remain significant markers for aggressiveness, studies on larger series of cases are mandatory to detect and validate new factors responsible for the variable course of MTC.

Clinical and immunohistopathological study of conjunctival melanocytic lesions in pediatric and adolescent patients. A case series.

BACKGROUND: Conjunctival pigmented neoplasia can be benign, premalignant or malignant tumors. Our study aims to establish the epidemiological, gross morphological and immunohistopathological features of the conjunctival pigmented lesions in pediatric and adolescent patients (<18 years), to establish an accurate diagnosis. PATIENTS, MATERIAL AND METHODS: This is a retrospective case series study conducted within two Ophthalmology Clinics from Iasi, Romania, on seven pediatric and adolescent patients. Using the Clinical Observation Chart and the Pathology Registers over a six-years period (January 2015-December 2021), we noted the patients' demographic data, clinical data, and ophthalmological investigations of the lesion, as well as the type of their treatment. All histological sections stained with Hematoxylin-Eosin (HE) and with five antibodies [pan-cytokeratin (pan-CK) AE1∕AE3, S100 protein, Melan A, human melanoma black 45 (HMB45), and Ki67] were re-examined by four pathologists for each case, to identify the type of the conjunctival lesion and its histological and immunohistochemical features. RESULTS: The mean age of all patients was 10.28 years, and the female∕male ratio was 1.3. Right eye was more often affected (71.42%). 71.42% of cases presented an elevated lesion, 57.14% of cases showed a lightly pigmented lesion, but 14.28% of cases exhibited a pink lesion and this feature described the inflamed juvenile conjunctival nevus. In all cases (100%) the conjunctival pigmented tumor was removed with safety margins. The microscopic examination revealed a compound melanocytic nevus in 57.14% cases, a junctional conjunctival nevus in 14.28% cases, an inflamed juvenile nevus in 14.28% cases, and a conjunctival melanoma arising from a pre-existing nevus in 14.28% cases. In all cases of nevi, the nevoid melanocytes showed strong immunopositivity for Melan A and S100 protein, variable and weak immunopositivity for HMB45, and a mean Ki67 labeling index of 1.71%. Conjunctival melanoma revealed strong immunopositivity of tumor cells for HMB45, Melan A and S100 protein, and a Ki67 labeling index of 20%. In all cases, the conjunctival epithelium showed strong immunopositivity for pan-CK AE1∕AE3. All our cases (100%) had a favorable outcome after the surgical removal of the tumor. CONCLUSIONS: Any excision of a conjunctival pigmented lesion must be subject to a systematic immunohistopathological examination, and there is a set of antibodies (anti-HMB45 and anti-Ki67) that are useful for differential diagnosis between a conjunctival nevus and a conjunctival melanoma.

EpCAM (MOC-31) - immunohistochemical profile and clinico-pathological correlations in different histological variants of papillary thyroid carcinoma.

EpCAM is a cell-adhesion molecule, located at the basolateral membrane of the normal epithelial cells. Changes in EpCAM expression are reported in several malignancies, as an early indicator for carcinogenesis. Our study aimed to evaluate the EpCAM expression in different subtypes of papillary thyroid carcinoma (PTC), focusing on its role in the risk stratification of the histological variants and its relationship with the classical clinico-pathological characteristics. We analyzed 70 selected cases of PTC, divided into low- and high-risk groups, according to histological criteria. Immunohistochemical (IHC) exam was performed using MOC-31 antibody, against the EpEx-MOC-31 extracellular domain of EpCAM molecule. MOC-31 expression was assessed at the membrane and cytoplasmic levels, using a semi-quantitative score that allowed the classification in low- and high-score category, respectively. The relationship between MOC-31 expression and clinico-pathological characteristics was statistically evaluated. We found statistically significant correlation between MOC-31 expression (low versus high) and the risk groups, tumor size and tumor relapse. The twofold analysis, based on score system and risk category, showed an association between low score and low risk in 80% of all cases, low score and high risk in 56% of the cases, high score and low risk in 36% of the cases and high score and high risk in 44% of the cases. The modification of MOC-31 location, with consequent changes in its interactions with other cell-adhesion molecules, is integrated in the carcinogenic mechanism. Our study demonstrates the large variability of MOC-31 expression in PTC histological variants, and highlights the differences between the low and high MOC-31 expression that could work as a useful tool for the identification of those high-risk PTC cases, with unfavorable clinical outcome.

Pediatric leukemia cutis: A case series.

BACKGROUND: Pediatric leukemia cutis (LC) is often difficult to diagnose due to similarity in appearance to other dermatologic diseases. Several case reports and smaller case series have been published in the medical literature, but studies on larger cohorts of children with LC are lacking. OBJECTIVE: This study aimed to better characterize the clinical features, course, and prognosis of LC in the pediatric population. METHODS: We performed a retrospective case series of 31 patients diagnosed with LC at Boston Children's Hospital and the Children's Hospital of Philadelphia. RESULTS: The number and morphology of LC lesions varied among patients, with the head and lower extremities being the most common sites of involvement. Leukemia cutis presented concomitantly with systemic leukemia in the majority of cases. Most cases of LC arose during initial leukemia episodes, rather than with relapsed leukemia. Acute myeloid leukemia was the subtype most frequently associated with LC, followed by acute lymphoblastic leukemia. Diagnosis altered treatment timing and therapeutic decisions. CONCLUSION: Children most often present concomitantly with LC and systemic leukemia. Since the morphology and distribution of LC varies, physicians must maintain a high index of suspicion for this diagnosis, as the presence of LC may change the management of systemic leukemia.

Prognostic significance of cell-adhesion molecules in histological variants of papillary thyroid carcinoma.

The molecular structure of E-cadherin and its function are intimately related to ß-catenin, their interactions ensuring the cell morphology and stability. Alterations of E-cadherin-ß-catenin complex facilitate the tumor growth and spreading in the carcinogenic mechanism. We aimed to assess the E-cadherin and ß-catenin immunoexpressions in different variants of papillary thyroid carcinoma (PTC), and the relationship of these markers with the clinicopathological prognostic factors. Our study group included 70 cases of PTC divided into two risk groups. The low-risk group comprised 45 cases diagnosed as conventional, follicular, oncocytic, macrofollicular, and clear cell variants, whereas the high-risk group consisted of 25 cases diagnosed as tall cell, follicular angioinvasive, cribriform-morular, hobnail, diffuse sclerosing, and solid subtype, respectively. Immunohistochemical exam was performed by using anti-E-cadherin and anti-ß-catenin antibodies, and their expressions were semi-quantitatively evaluated. The association between E-cadherin and ß-catenin, respectively, and clinicopathological prognostic factors was statistically analyzed. We noted statistically significant differences between membranous E-cadherin expression (low versus high) and tumor size, histological risk groups, tumor stage, lymph node metastases, vascular invasion and tumor relapse. We also found statistically significant correlation between membranous ß-catenin expression (low versus high) and the risk groups, tumor size and tumor stage, but no associations of cytoplasmic ß-catenin (low versus high) with the clinicopathological characteristics. Our study demonstrates that E-cadherin and ß-catenin expressions differ in low- and high-risk groups of PTC. The aggressive behavior of the high-risk histological variants is associated with reduced membranous E-cadherin, and loss of membranous ß-catenin followed by enhanced cytoplasmic expression. These results open large standpoints for a deeper characterization of the histological variants of PTC.

HER-2÷neu expression in different histological subtypes of papillary thyroid carcinoma.

The identification and validation of new, complementary prognostic factors represents a challenging issue in thyroid pathology, opening the perspective of papillary thyroid carcinoma (PTC) stratification based on differences of aggressiveness at molecular level. Our study aims to analyze the HER-2÷neu expression in different subtypes of PTC and its relationship with the classical clinicopathological factors. We investigated 120 cases of sporadic PTC. The cases were selected based on the histological criteria reported to clinical course and prognosis and distributed in two different subgroups, namely low- and high-risk. HER-2÷neu expression was assessed using an adapted semiquantitative score proposed for thyroid carcinomas. The correlations between HER-2÷neu expression and clinicopathological prognostic factors were statistically analyzed. HER-2÷neu positivity was found in 25 (20.8%) cases, from which 20 cases were classified as subtypes with low-risk and five with high-risk; 95 (79.2%) cases were HER-2÷neu negative, 53 cases being included in low- and 42 cases, respectively, in high-risk group. HER-2÷neu expression was significantly associated with histological subtypes, extrathyroidal extension, and tumor focality. Our results highlight the potential of HER-2÷neu as supplementary marker useful for the stratification of PTC in low-risk and high-risk histological groups, along with the well-known clinicopathological prognostic factors. Our data could be considered as new evidences that indicate different involvement of HER-2÷neu in tumor development and behavior, possible due to its connection with other factors present in the molecular environment.

Relationships between clinicopathological prognostic factors in papillary thyroid microcarcinoma: a refined analysis based on 428 cases.

A clear definition of the prognostic factors for papillary thyroid microcarcinoma (PTMC) is still debatable, as the tumor characteristics which indicate a high risk of metastasis are little known. We investigated the clinicopathological profile of a large group of PTMC, aiming to ascertain possible relationships between a set of clinicopathological characteristics and four parameters expressing tumor extension and aggressiveness (namely lympho-vascular invasion, thyroid capsule invasion, extrathyroidal extension and lymph node metastasis). For 428 patients, the following data were retrospectively documented: sex, age, tumor size, histological variant, associated thyroid pathology, location (subcapsular, intraparenchymal), unilateral or bilateral involvement, number of foci, lympho-vascular invasion, thyroid capsule invasion, extrathyroidal extension and lymph node metastasis. Data were analyzed using univariate and multivariate logistic regression analysis. Multivariate analysis confirmed that the tumor size is a negative prognostic factor for lympho-vascular invasion, thyroid capsule invasion, extrathyroidal extension and lymph node metastasis. We also demonstrated a strong relationship between the subcapsular location and lympho-vascular and capsule invasion, and extrathyroidal extension. The multifocality was correlated only with thyroid capsule invasion and extrathyroidal extension. Regarding the histological variants, the only validated correlation was between the oncocytic variant and extrathyroidal extension. Our work contributes to the validation of PTMC prognostic factors, useful in stratification of PTMC in high or low risk classes, and able to explain the behavioral differences in the tumor development.

Heterogeneous Periostin Expression in Different Histological Variants of Papillary Thyroid Carcinoma.

BACKGROUND: Periostin (PN) epithelial and stromal overexpression in tumor pathology has been studied according to tumor growth, angiogenesis, invasiveness, and metastasis, but a limited number of studies address PN in thyroid tumors. AIM: Our study aimed to analyze PN expression in different histological variants of PTC and to correlate its expression with the clinicopathological prognostic factors. MATERIAL AND METHODS: PN expression has been immunohistochemically assessed in 50 cases of PTC (conventional, follicular, oncocytic, macrofollicular, and tall cell variants), in tumor epithelial cells and intratumoral stroma. The association between PN expression and clinicopathological characteristics has been evaluated. RESULTS: Our results show that PTC presented different patterns of PN immunoreaction, stromal PN being significantly associated with advanced tumor stage and extrathyroidal extension. No correlations were found between PN overexpression in tumor epithelial cells and clinicopathological features, except for specific histological variants, the highest risk of poor outcome being registered for the conventional subtype in comparison to the oncocytic type. CONCLUSIONS: Our study demonstrates differences in PN expression in histological subtypes of PTC. Our results plead in favor of a dominant protumorigenic role of stromal PN, while the action of epithelial PN is less noticeable.