Thyroid Collision Tumors: The Presence of the Medullary Thyroid Carcinoma Component Negatively Influences the Prognosis.

Thyroid collision tumors (TCTs) are rare pathological findings, representing <1% of thyroid cancers. This study aimed to compare the main pathological features of TCTs containing medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) components with MTC-only tumors and PTC-only tumors. Methods: The retrospective study included 69 cases diagnosed with TCTs (with simultaneous MTC and PTC components), MTC and PTC. All tumors were comparatively assessed for the classical histopathological prognostic features, including a new grading system for MTC. Results: The main component of TCTs had more frequent microscopic extrathyroidal extension (mETE) (p = 0.000), lymphovascular invasion (LVI) (p = 0.000), perineural invasion (PNI) (p = 0.044), and lymph node metastasis (p = 0.042). Additionally, the TCTs' MTC component presented with more frequent LVI (p = 0.010). Comparing TCTs' MTC and PTC components with MTC-only tumors and PTC-only tumors revealed that only the TCTs' MTC components had statistically significant more frequent mETE (p = 0.010) than MTC-only tumors. When applied to the MTC component of TCTs, the pathological parameters of the new grading system of MTC showed no correlations with other microscopic or clinical aspects. Conclusion: Using classical pathological prognostic features, the comparative analysis revealed that the main TCTs' component was more aggressive than the minor one. Contrary to PTCs, in TCTs, the medullary component was more aggressive than the papillary one, but also more aggressive than MTC-only tumors.

Is High Expression of Claudin-7 in Advanced Colorectal Carcinoma Associated with a Poor Survival Rate? A Comparative Statistical and Artificial Intelligence Study.

AIM: The need for predictive and prognostic biomarkers in colorectal carcinoma (CRC) brought us to an era where the use of artificial intelligence (AI) models is increasing. We investigated the expression of Claudin-7, a tight junction component, which plays a crucial role in maintaining the integrity of normal epithelial mucosa, and its potential prognostic role in advanced CRCs, by drawing a parallel between statistical and AI algorithms. METHODS: Claudin-7 immunohistochemical expression was evaluated in the tumor core and invasion front of CRCs from 84 patients and correlated with clinicopathological parameters and survival. The results were compared with those obtained by using various AI algorithms. RESULTS: the Kaplan-Meier univariate survival analysis showed a significant correlation between survival and Claudin-7 intensity in the invasive front (p = 0.00), a higher expression being associated with a worse prognosis, while Claudin-7 intensity in the tumor core had no impact on survival. In contrast, AI models could not predict the same outcome on survival. CONCLUSION: The study showed through statistical means that the immunohistochemical overexpression of Claudin-7 in the tumor invasive front may represent a poor prognostic factor in advanced stages of CRCs, contrary to AI models which could not predict the same outcome, probably because of the small number of patients included in our cohort.

Complete oculomotor nerve palsy - first manifestation of gastric adenocarcinoma: clinical experience and literature review.

The diagnosis and management of the alteration of the normal function of the oculomotor nerve (third cranial nerve) varies depending on the characteristics of the paralysis, the age of the patient, and the associated symptoms and signs. Oculomotor nerve palsy may be caused by lesions located anywhere from the oculomotor nucleus to the termination of the third nerve in the extraocular muscles. Although there have been significant advances in neuroimaging to facilitate early diagnosis, the management of a patient presenting with isolated oculomotor palsy is still challenging. This review tackles the case of a 52-year-old patient, with a history of pulmonary tuberculosis (at the age of five), referred to the Department of Ophthalmology, St. Spiridon Emergency Clinical Hospital, Iasi, Romania. The patient had diplopia accompanied by right eyelid ptosis, symptoms that began suddenly 10 days before hospitalization. The clinical examination showed right eye grade II palpebral ptosis, exotropia with limitation of eyeball movements in adduction, supra-∕infraduction. Biomicroscopic examination of the anterior pole revealed the presence of anisocoria and light-near dissociation on the affected side. Numerous investigations were performed to identify the cause, starting with tumoral markers, which were within normal limits. Magnetic resonance angiography (MRA) was performed, and posterior communicating artery aneurysm was ruled out. The endocrinology examination and hormonal laboratory tests were also within normal parameters. Due to suspicions of generalized tuberculosis raised by the infectious disease doctor or presence of secondary lesions, thoraco-abdomino-pelvic computed tomography (CT) scan with contrast agent was done and its findings required gastroenterological exploration. After various explorations, the certainty diagnosis was set by histopathological examination, which revealed gastric adenocarcinoma.

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.

Thymus pathology in myasthenia gravis with anti-acetylcholine receptor antibodies and concomitant Hashimoto's thyroiditis. A four-case series and literature review.

OBJECTIVE: Identifying the morphological features of thymus in patients with myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) antibodies and concomitant Hashimoto's thyroiditis (HT), which were recruited from a single surgical unit of a tertiary referral hospital located in the North-Eastern region of Romania, over a period of 11 years. PATIENTS, MATERIALS AND METHODS: We retrospectively reviewed clinical, imaging, laboratory, thymic pathology, and outcome data that were obtained from medical records of patients with MG and concomitant HT, to whom a thymectomy was performed for a suspected thymic lesion. All the surgical interventions were done in the Third Clinic of Surgery, St. Spiridon Emergency County Hospital, Iasi, Romania, for an 11 years' period, i.e., from January 1, 2000 and December 31, 2010. RESULTS: Four patients (three females and one male) were included. The mean age of the patients at the time of their thymectomy was 40.25 years. Of all patients, 75% had moderate or severe MG, 100% had anti-AChR antibodies, and an electromyographic decrement greater than 25%. All patients have been diagnosed with HT in their past medical history by a full thyroid panel [high thyroid-stimulating hormone (TSH) values, low free thyroxine (fT4) values, and the presence of the anti-thyroid antibodies] and all of them have been treated with Euthyrox. Our four patients expressed different MG subtypes, each of them being associated with different thymus pathology. Thoracic computed tomography (CT) scan revealed heterogeneous mediastinal masses and established the correct diagnosis only in 25% of cases. The pathological exams also revealed a heterogeneous pattern of thymic lesions. In contrast with other studies, our patients with MG with anti-AChR antibodies and concomitant HT presented atrophic thymus more frequently (50%), but with particular morphological changes of Hassall's corpuscles. Also, 25% of cases were diagnosed with thymic lympho-follicular hyperplasia (TLFH) associated with thymic epithelial hyperplasia. In B2 thymoma, neoplastic epithelial cells expressed cytokeratin 19 (CK19) immunoreactivity, high Ki67 labeling index and strong p63 immunopositivity. CONCLUSIONS: In our series, MG and HT occurred simultaneously, or one of them was diagnosed before the other, raising some new questions regarding the immune mechanism of these two autoimmune diseases. Due to the heterogeneous morphological changes of the thymus that we found in this study, we can hypothesize that thymus is involved in the pathogenic mechanism of MG with anti-AChR-antibodies and concomitant HT development.

Clinical, histopathological and immunohistochemical features of brain metastases originating in colorectal cancer: a series of 27 consecutive cases.

INTRODUCTION: Brain metastases (BMs) originating in colorectal cancer (CRC) have a significant importance for patients' survival. Because in literature there are only isolated case reports and only few series published on this issue, we aimed to assess the incidence of BMs from CRC, to identify patient's characteristics and BMs clinical, histopathological (HP) and immunohistochemical (IHC) features, and to compare the data we obtained with those from literature. PATIENTS, MATERIALS AND METHODS: We present a retrospective study of 27 histologically confirmed cases of BMs from CRC among all 1040 patients who received metastasectomy in the Department of Neurosurgery, Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, in an eight-year period (January 2011 to December 2018). Patients' characteristics (gender, age), primary tumor location, time from primary tumor surgery to BMs surgery and BMs features (number, location and HP characteristics) were investigated. Histochemical [Alcian Blue (AB) and Periodic Acid-Schiff (PAS)] staining and IHC stainings for cytokeratin (CK) 7, CK20, caudal-type homeobox 2 (CDX2) and human epidermal growth factor receptor 2 (HER2)∕neu were performed on all available BMs specimens. RESULTS: There were 27 consecutive patients with BMs from CRC, corresponding to 2.59% of all patients with BMs during the eight-year period we have studied, most of them being diagnosed and treated in 2016. Male:female ratio was 1.45. The mean age for all patients at diagnosis of the BMs was 62.25 years (range: 40-79 years). The origin of the primary cancer was mainly the colon (62.96% of all cases). Of all 27 patients, only two (7.4%) presented neurological symptoms without a diagnosis of CRC. BMs were identified in a period ranging from six months to 70 months after the initial diagnosis. The average time between diagnosis of the primary tumor and of the BMs was 25.92 months. At the moment of the diagnosis of BMs, 17 (62.96%) patients also had other systemic metastases. Most of the cases (55.55%) were situated in the supratentorial compartment. IHC stainings were negative for CK7 and positive for CK20 and CDX2 in all BMs from colonic adenocarcinomas (ADCs), a profile consistent with a non-neuronal and gastric origin. AB and PAS stainings revealed pools of extracellular mucin, especially in cases of mucinous ADC. Ki67 labeling index ranged between 90% and 100%. IHC staining with anti-HER2∕neu antibody showed in 25 (96.15%) cases a strong and diffuse aberrant nuclear staining. CONCLUSIONS: BMs originating in CRC represent a rare pathology and have particular clinical and IHC features that could vary from one series to another series. In a few cases, BMs may be diagnosed in the absence of a known CRC diagnosis and in these situations, the correct diagnosis is of interest. However, a panel of antibodies can help in establishing a correct diagnosis. Our study was among the first to analyze the HER2∕neu expression pattern in BMs from CRC and we found a strong aberrant nuclear expression of this molecular marker on IHC investigation. Related to the data published so far in the literature, it is possible that HER2∕neu aberrant expression in the tumor nuclei of the BMs from our series may express the metastatic tumor cell phenotype that was previously subjected to cytostatics and radiation therapies. As such, we suggest that HER2∕neu aberrant expression in BMs originating in CRC could represent a proof for the worst prognosis of these patients.

Protective role of selenium on thyroid morphology in iodine-induced autoimmune thyroiditis in Wistar rats.

Excess iodine may induce and exacerbate autoimmune thyroiditis (AIT) in humans and animals. In order to assess the potential protective mechanisms of selenium (Se) in thyroid autoimmunity, the effects of inorganic Se (sodium selenite) administration on thyroid morphology and follicular cytology were investigated in adult Wistar rats with iodine-induced AIT. A total of 48 adult Wistar rats (24 females, 24 males) were allocated to one of four dietary regimens: C0, control; C1, only potassium iodine (KI); C2, concomitant KI and Se; C3, only KI initially, followed by Se administration. For AIT induction the rats were fed with 0.05% KI for 56 days. Se-treated rats received 0.3 mg/l sodium selenite in drinking water. Thyroid tissues were collected for pathologic diagnosis after 7 days in C0 group, 56 days in C1 and C2 groups, and 112 days in C3 group. In C1 group, moderate to severe thyroiditis was observed in 83% of males and 50% of female rats (P=0.223). In C3 group 16.7% of male rats developed moderate thyroiditis and none in C2 group, whereas no females were identified with moderate to severe thyroiditis in C2 or C3 group. Thus, the administration of Se was proven to have protective effects against thyroiditis cytology in both male and female Wistar rats.

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.

Protean cytological, histological and immunohistochemical appearances of medullary thyroid carcinoma: current updates.

Medullary thyroid carcinoma (MTC) accounts for only 0.5-3% of all malignant diseases, but is responsible for more deaths every year than all the other endocrine malignancies taken together. Approximately 75-80% of MTCs occur sporadically, while the inherited forms of MTC are responsible for the rest of the cases. The heritable MTC results from a germline mutation in the rearranged during transfection (RET) proto-oncogene and is included into the multiple endocrine neoplasia 2 (MEN2), being associated with other endocrine abnormalities and clinical features. MTC is a neuroendocrine tumor that releases a wide range of secretory products that are responsible for a variety of symptoms, making it difficult to be diagnosed. For this reason, the pathological analysis is of vital importance to ensure that the correct diagnosis is made. This review presents the main data from the contemporary literature related to the pathological diagnosis of a patient with MTC and highlights the wide range of tumor cytological features, the many histological variants, as well as the particular tumor immunophenotype. It also reveals the new approach to this type of cancer in the new World Health Organization (WHO) Classification of Thyroid Tumors (2017) and the reassessment of MTC tumor category in the new American Joint Committee on Cancer∕Tumor, Node, Metastasis (AJCC∕TNM) Staging (2017).

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.

Ovarian strumal carcinoid - case report.

Strumal carcinoid represents a rare form of ovarian teratoma, consisting of both thyroid tissue and carcinoid structures. The carcinoid component is a well-differentiated neuroendocrine tumor with excellent prognosis. Strumal carcinoid tumors are commonly found in peri-menopausal women who are not usually interested in preserving their fertility and who are thus open to radical surgical treatment. In this report, we present a 24-year-old, nulliparous patient with strumal carcinoid, confirmed by histopathology and a large panel of immunohistochemistry (IHC) markers, who wished to preserve her fertility. In this case, a conservative surgical treatment (salpingo-oophorectomy) served to preserve vital and reproductive prognosis, and correct tumor classification was of extreme importance. The morphological examination of strumal carcinoid showed struma ovarii with a thyroid follicle-like structure [positive for thyroid transcription factor 1 (TTF1), thyroglobulin, CD56, cytokeratin (CK) 19, and negative for Hector Battifora and mesothelioma 1 (HBME1)], and a neuroendocrine cell component with a trabecular arrangement and island growth (positive for synaptophysin, chromogranin, CD56, and CK7 negative), which were interlocked and intimately associated. Papillary thyroid carcinoma of follicular type was ruled out by CD56 positivity and HBME1 negativity. Medullary thyroid carcinoma with strumal component was excluded by calcitonin negative staining. Solid rosette-like structures with negative glial fibrillary acidic protein (GFAP) staining ruled out a neuroectodermal component. A multilocular mucinous cystadenoma was identified without other teratoma components. Strumal carcinoid requires a meticulous examination to rule out other entities with malignant behavior and poor prognosis. In this case, a conservative treatment is sufficient to remove the tumor, preserving vital and reproductive prognosis.

Cytological, histopathological and immunological aspects of autoimmune thyroiditis: a review.

Autoimmune thyroiditis (AT) is a disease that may be associated with many other autoimmune endocrine and non-endocrine disorders. This disease is mediated by both humoral and cellular mechanisms and it is the result of combined effects of human leukocyte antigen (HLA) class II genes and non-HLA genes polymorphisms. The clinical course of AT is variable and may be characterized by spontaneous remission and by irreversible thyroid insufficiency as the consequence of atrophic and fibrous transformation of the thyroid gland in other cases. In this paper, the AT's etiology and immunological mechanism along with its cytological and histopathological features are reviewed in order to increase our understanding about the mechanism involved in pathogenesis of this disease and to open new directions of investigations that will be useful in a better clinical practice.

Long-term survival in a patient with advanced gastric cancer and metachronous right-sided colon cancer.

Gastrointestinal carcinomas represent the most common cancers worldwide. The coexistence of gastric cancer with metachronous colon cancer represents a rare phenomenon, and the prognosis of the patient is poor. We present here a case of an elderly patient with primary gastric intestinal type well-differentiated adenocarcinoma (pT3N0, stage IIA) who developed a metachronous right-sided colon cancer diagnosed and treated after 11 years from the first surgical intervention. Histopathological and immunohistochemical examination revealed a well-differentiated adenocarcinoma (strongly positive staining for cytokeratin 20 and CDX2), pT3N0 stage IIA. The patient is still alive and active after 16 years from his first surgical intervention, even though no treatment has done after the removal of his second cancer. In conclusion, in any case of gastric cancer, first the surgeon, and then the general practitioner should be alert to recognize a second primary tumor with different origin and to perform complete postoperative control. The correct diagnosis could lead to the patients' best prognosis.

The value of PAX8 and WT1 molecules in ovarian cancer diagnosis.

PAX8 and WT1 are transcription factors, each of them with distinct roles in organogenesis, morphogenesis, cell growth, and differentiation. Recently, their expression was also confirmed in a variety of malignancies, being included in the antibodies panel recommended for the female genital tract pathology. The aim of our study was to evaluate PAX8 and WT1 in different types of ovarian cancer (OC) with focus on (i) the completion of evidences of the Müllerian origin and (ii) the establishment of primary ovarian tumor status vs. metastasis. The study group consisted of 86 cases, with histopathological diagnosis covering the main subtypes of OC (low- and high-grade serous, low- and high-grade endometrioid, clear cell, mucinous, malignant Brenner tumor, malignant mixed Müllerian tumor, undifferentiated, and borderline). The investigation was based on immunohistochemical examination, performed by using specific antibodies applied on blocks obtained through Tissue MicroArray technique, and interpreted by scores assessing the nuclear positivity of tumoral cells. One case was not valuable due to technical difficulties. PAX8 expression was positive in 70 (81.39%) cases, the remaining 15 (17.44%) negative cases suggesting a non-Müllerian origin. WT1 expression was positive in 61 (71%) cases, mainly expressed in serous carcinoma, regardless of their differentiation degree, and negative in 24 (27%) cases. Our study provide supplementary evidences to support the association of PAX8 and WT1 immunostaining in the investigation of the complex biology of OC, PAX8 confirming the ovarian primary and WT1 allowing the refinement of the diagnosis in phenotype overlapping cases.