Metastatic onset of prostate carcinoma: A clinical and pathological challenge.

INTRODUCTION: Prostate cancer is the second most common cancer, following lung cancer, and the fifth leading cause of cancer death in men worldwide. The onset of the disease, characterized by symptoms or changes caused by distant metastases, is rare and poses a challenge for clinicians and pathologists. We aimed to present a series of prostate carcinoma (PC) with unusual, histologically confirmed distant metastases (pM1) at the time of diagnosis, which raised suspicions of other types or origins of the primary tumor. MATERIALS AND METHODS: Patients diagnosed with PC and distant metastases within a five-year timeframe (2017-2022) were extracted from the hospital database. The following data were collected: patient's age, imaging data, serum PSA level, and histopathological evaluation results. Patients with unusual distant metastases were selected and analyzed. RESULTS: We identified 10 patients in whom the diagnosis of PC was established following histopathological examination of tissue taken from distant metastatic sites (pM1). In three patients, the location of distant metastases was unusual: retroperitoneal, cranial/dural/epicranial and supradiaphragmatic lymph nodes which posed diagnostic challenges. Establishing the prostate origin of the tumor relied on immunohistochemical (IHC) investigation guided by clinical-imaging information. CONCLUSIONS: A metastasis of PC may rarely present as a cranial/dural tumor, retroperitoneal, or supradiaphragmatic lymphadenopathies in a man over the age of 50, but it should be taken into consideration. In the absence of correlated clinical, imaging, and histopathological/IHC data, diagnosing distant metastasis from PC is difficult, especially considering its potentially confusing IHC profile.

Clinical-Pathological Features of Thyroid Neoplasms in Young Patients Diagnosed in a Single Center.

Background and objectives: The aim of this study was to evaluate the clinical-pathological profile in young patients with thyroid cancer. Materials and methods: We realized a retrospective study on patients with thyroid neoplasms who underwent surgery at the "Pius Brinzeu" County Clinical Emergency Hospital in Timisoara, Romania. A comparative analysis of some parameters between two groups, young patients (<45 years) versus patients ≥45 years, was performed. Results: A total of 211 patients met the study inclusion criteria, mostly females (86.26%) with a female/male ratio of 6.81:1. In patients <45 years old (25.64%), papillary thyroid carcinoma was identified in 51.85% of cases; in 53.85% of cases, the tumor was >1 cm; 13.46% had extrathyroidal extension (p = 0.0430); 21.15% capsule invasion (p = 0.1756); 23.08% lympho-vascular invasion (p = 0.0048); and 13.46% of cases locoregional nodal invasion (p = 0.0092). Conclusions: Thyroid cancer in young people was associated with chronic lymphocytic thyroiditis and tumor progression parameters, identifying more cases of extrathyroidal extension, locoregional nodal invasion, lympho-vascular invasion and perineural invasion in young patients compared to older ones. For a better understanding of this pathology and to improve diagnosis and therapeutic management, more studies are needed for these patients.

Primary Thyroid Lymphoma: A Retrospective-Observational Study in a Single Institutional Center.

Background and Objectives: primary thyroid lymphoma (PTL) is a rare neoplasm, displaying a variety of histological features. It is often a challenge for pathologists to diagnose this tumor. Materials and Methods: this study is a retrospective analysis of clinical and pathological characteristics of a group of eleven patients (eight women and three men, mean age 68 years, range 50-80 years) diagnosed with PTL. Results: nine patients (81.81%) presented a tumor with progressive growth in the anterior cervical region, usually painless and accompanied by local compressive signs. Histologically, we identified six cases (55%) of diffuse large B-cell lymphoma, three cases (27%) of extranodal marginal zone lymphoma, one case (9%) of follicular lymphoma, and one case (9%) of mixed follicular-diffuse lymphoma. PTL was associated with microscopic Hashimoto autoimmune thyroiditis in ten cases (90.9%). Ten patients (90.9%) presented with localized disease (stage I-IIE). A percentage of 60% of patients survived over 5 years. We observed an overall longer survival in patients under 70 years of age. Conclusions: PTL represents a diagnosis that needs to be taken into account, especially in women with a history of Hashimoto autoimmune thyroiditis, presenting a cervical tumor with progressive growth. PTL is a lymphoid neoplasia with favorable outcome, with relatively long survival if it is diagnosed at younger ages.

The impact of the COVID-19 pandemic on thyroid nodular disease: a retrospective study in a single center in the western part of Romania.

Introduction: The COVID-19 pandemic had a significant impact on the healthcare system, leading to a prioritization of hospital admissions in many countries. Romania was no exception, and it had to restrict patient access to medical services in hospitals with chronic diseases and oncological pathology, including thyroid cancer. This study aimed to compare the clinical and pathological factors of patients with nodular thyroid disease diagnosed and surgically treated during the two years before and after the COVID-19 pandemic, in a single medical institution. Methods: The retrospective study included 1505 patients who were diagnosed and operated on for nodular thyroid disease between January 2018 and December 2021. The patients were divided into two groups: the "PRECOVID" group (January 2018 to February 2020), and the "POSTCOVID" group (March 2020 to December 2021). The analyzed parameters included patients' gender, age, preoperative diagnosis, type of surgical intervention, and pathological diagnosis. Results: A significant decrease was observed in the number of surgeries performed for thyroid nodular disease during the COVID-19 pandemic period (450 versus 1055 cases, p<0.00001). There was a significant decrease in the number of surgical reinterventions (0.9% in the POSTCOVID group versus 2.9% in the PRECOVID group, p=0.01) and a significant increase in the number of total thyroidectomies (84.9% in the POSTCOVID group versus 80.1% in the PRECOVID group, p=0.02). We also observed a higher incidence of malignant/borderline tumors in the POSTCOVID group compared to the PRECOVID group (p=0.04) and a significantly higher frequency of aggressive forms of thyroid cancer in the POSTCOVID group (p=0.0006). Discussion: The COVID-19 pandemic had a significant impact on the surgical management of nodular thyroid disease, resulting in a decrease in surgeries and a change in the type of surgical interventions performed. The higher incidence of malignant/borderline tumors diagnosed during the pandemic highlights the importance of timely diagnosis and treatment of thyroid nodules to prevent cancer progression.

Incidental carcinoma of the prostate in cystoprostatectomy specimens - is it always a toothless lion?

Incidental prostate carcinoma (iPC) is a subject of debate concerning its definition, incidence, biology, diagnosis, staging, and treatment. The present study aimed to assess the incidence and main clinical-morphological characteristics of iPC identified in radical cystoprostatectomy (RCP) specimens over a 5-year period. Using the database of the Urology and Pathology Departments, we identified all patients with bladder carcinomas (BCs) who underwent RCP within a 5-year frame time. We selected only those patients with synchronous BC and prostate carcinoma (PC). The following parameters were analyzed for these patients: age, type of bladder and prostate tumor, degree of differentiation, pathological stage, and other prognostic parameters. We identified 91 men with bladder tumors treated by RCP among whom 43, aged between 53 and 84 years (mean age: 69.2 years), presented synchronous PC. iPC was more prevalent in older individuals (>65 years: 30 patients, 69.8%), with only six out of the 43 (12.8%) patients with iPC being aged ≤60 years. All iPC cases were conventional adenocarcinoma. Well-differentiated prostate adenocarcinomas (grade group 1) predominated (65.1%). Among the 43 iPCs, 16 (37.2%) were clinically significant PCs. iPC is frequently identified in patients with BC when inclusion and evaluation of all or most of the prostate tissue are performed. Although more than half of iPCs were well-differentiated tumors confined to the prostate, a significant number of cases met the criteria of clinically significant PC. All men over the age of 50 who are candidates for RCP, should undergo evaluation through serum prostate specific antigen determination.

An In Vivo Observational Histological Study of Peripheral Arterial Damage in Patients with Acute Limb Ischemia in SARS-CoV-2 Infection.

Thromboembolic events, such as acute limb ischemia, were reported worldwide in patients with COVID-19, suggesting that SARS-CoV-2 infection acts like a redoubtable prothrombotic factor in these patients. The aim of the study was to summarize the histopathological changes found in the arterial wall, intraarterial thrombus, and adjacent skeletal muscles. Considering the lack of evidence from in vivo studies, we performed observational histological research of peripheral arterial damage in patients with acute limb ischemia and SARS-CoV-2 infection. We investigated 22 patients with acute limb ischemia and SARS and harvested histopathological samples from those who agreed to this procedure. We performed histologic tissue harvesting during the revascularization procedure from the thrombosed area of the common femoral artery. Morphologic analysis was made on the hematoxylin-eosin (HE) stain. Special stains were also used-Elastica van Gieson (EvG) and Alcian Blue-Periodic Acid-Schiff (AB-PAS) and primary antibodies-CD45 and CD61. Our patients had significant risk factors for thrombus formation, since all of them had arterial hypertension, 81% had dyslipidemia, 73% were obese, 63% suffered from diabetes mellitus, and 45% were active smokers. The histological findings using immunohistochemistry (CD45 and CD68 reactions) or special and usual stains underlined the mechanism for ischemia production in SARS-CoV-2 patients. The main histological findings in our study were endothelial destruction and inflammation that were found in all analyzed structures.

Poorly differentiated clusters and tumor budding are important prognostic factors in colorectal carcinomas.

The aim of our study was to assess the prognostic value of the two new grading systems based on the quantification of tumor budding - TB (GBd) and poorly differentiated clusters - PDCs (PDCs-G) in colorectal carcinomas (CRC). We performed a retrospective study on 71 CRC patients who underwent surgery at the Emergency County Hospital, Timișoara. CRC cases were classified based on haematoxylin-eosin slides, using the conventional grading system, GBd and PDCs-G, respectively. We used two-tier and three-tier grading schemes for each system. Subsequently,  we evaluated  associations with other prognostic factors in CRC. Based on the three-tier GBd (GBd-3t)  most cases (34/69, 49.27%) were classified as G3Bd-3t, while based on the conventional grading system, the majority of the cases (55/69, 79.71%) were considered G2. On the other hand, based on the three-tier PDCs-G system (PDCs-G-3t), most cases (31/69, 44.93%) were PDCs-G2-3t. We also noted a more significant association of GBd-3t with other prognostic parameters analyzed, as compared to the conventional grading system. Nodal status, tumor stage, and lymphovascular invasion were strongly correlated with GBd-3t (p=0.0001). Furthermore, we noted that PDCs-G-3t correlated more significantly than the conventional grading system with nodal status (p<0.0001), tumor stage (p=0.0003), lymphovascular invasion (p<0.0001), perineural invasion (p=0.005) and the tumor border configuration (p<0.0001). High GBd and PDCs-G grades correlate directly with other negative prognostic factors in CRC.Thus, these new parameters/classification methods could be used as additional tools for risk stratification in patients with CRC.

Immunohistochemical expression of chemokine receptor in neuroendocrine neoplasms (CXCR4) of the gastrointestinal tract: a retrospective study of 71 cases.

AIM: C-X-C motif chemokine receptor 4 (CXCR4) is expressed in many tumor entities, including gastrointestinal neuroendocrine neoplasms (GI-NENs). However, the role of CXCR4 expression in GI-NENs has been less studied. Our objective was to investigate the expression of CXCR4 in a series of GI-NENs with various clinical and pathological features. METHODS: The immunohistochemical (IHC) expression of CXCR4 (clone UMB2) was examined in 71 GI-NENs and a semiquantitative immunoreactivity score (IRS) was calculated taking into consideration the intensity of the IHC reaction and the percentage of the tumor cells which showed positive expression. Results were compared with several clinical and pathological prognostic factors. RESULTS: High CXCR4 expression was noted in 31 (43.7%) cases. Low IRS values were more frequent in NENs from the small intestine (66.7%) and stomach (60%). Also, all appendix tumors had IRS value of zero. High CXCR4 expression was noticed in 52.5% of liver metastases, compared to 40.4% primary tumors. A significant relationship was observed between the CXCR4 expression and the tumor grade (p=0.0216), and high IRS value was correlated with clinical stages III and IV (p=0.0142) and lympho-vascular invasion (p=0.0129). 74.1% of G1 neuroendocrine tumors (NETs) had a low IRS, G3 NETs showed minor differences between low (42.9%) and high (57.1%) expression and 66.7% of neuroendocrine carcinomas (NECs) presented high expression of CXCR4. CONCLUSIONS: The present study highlighted that high CXCR4 expression is associated with high grade and advanced stage GI-NENs, as well as with metastatic cases. In these cases, high CXCR4 expression could serve as an important target for CXCR4 antagonists.

Multiple Primary Tumors Originating From the Prostate and Colorectum A Clinical-Pathological and Therapeutic Challenge.

Considering that the incidence of colorectal (CRC) and prostatic cancer (PC) increases with age, metachronous and synchronous tumors can often affect the same patient. Despite the importance of this subject for the diagnosis and management of oncologic patients, in medical literature the data are scarce. The aim of the study was to evaluate the incidence and the characteristics of double/multiple primary malignant tumors (D/MPMTs) with colorectal and prostatic origin, in patients admitted to a reference hospital in West Romania. A 4-year retrospective observational study (2016-2019) was conducted by analyzing the medical records of all patients admitted in the hospital. Demographic and clinical data, as well as tumor-related parameters, were extracted. We identified 413 consecutive hospitalized patients with PC, and 21 (5%) of them also had a primary CRC. At the time of diagnosis, the mean age of the patients with PC was 71.2 ± 6 years, and 71.8 ± 10 years for patients with CRC. Synchronous PC and CRC tumors were identified in 3/21 cases and metachronous tumors in 18/21 cases. Prostate cancer was the first tumor to be diagnosed in 13/18 cases and CRC in 5/18 cases. The most frequent subtype of PC was acinar adenocarcinoma (90%) and for CRC cases, conventional adenocarcinoma (90%). Prostate and colorectal cancers tend to co-occur in a single patient. The diagnosis of one of these two types of tumors should imply the screening for the other one, because these patients require a multidisciplinary and personalized approach.

The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5.

The 2019 World Health Organization (WHO) classification of gastrointestinal tumors defines well-differentiated grade 3 neuroendocrine tumors, the mixed neuroendocrine-non-neuroendocrine tumors (MiNENs) and classifies goblet cell carcinoid as goblet cell adenocarcinoma. The expression of somatostatin receptors (SSTRs) is the foundation for somatostatin analogue therapy. At present, there are only a few studies that have analyzed the immunohistochemical reactivity of SSTRs in gastrointestinal neuroendocrine neoplasms (NENs). The aim of the present study was to evaluate the immunohistochemical expression of SSTR2 and SSTR5 in gastrointestinal NENs and goblet cell adenocarcinomas and the correlation of these markers with clinical and morphological factors. The study included 67 patients with NENs and 4 patients with adenocarcinoma ex-goblet cell carcinoid diagnosed between January 2008 and December 2018. Tumors were reclassified according to the 2019 WHO classification. Immunohistochemical staining for chromogranin A, synaptophysin, Ki-67, p53, SSTR2, and SSTR5 were performed in all the cases. The results showed that, G1 and G2 neuroendocrine tumors were more common SSTR2-positive in comparison with G3 carcinomas (P<0.0001). In addition, 33.3% of neuroendocrine carcinomas and 2 cases of low-grade adenocarcinoma ex-goblet cell carcinoid were SSTR2-positive. Neuroendocrine carcinomas had significantly lower SSTR2 and SSTR5 expression compared with well-differentiated neuroendocrine tumors (P=0.0130; P=0.0437, respectively). The SSTR2 expression in the early tumor stages was 100%, more often than in advanced stages (55.6%; P=0.0011). The results demonstrated the decrease in SSTR2 expression with increasing malignancy and tumor stage. The SSTR2-positive expression in neuroendocrine carcinomas and adenocarcinoma ex-goblet cell carcinoid provides evidence for the benefits of somatostatin analog treatment associated with surgery and chemotherapy.

Sclerosing Extramedullary Hematopoietic Tumor (SEHT) Mimicking a Malignant Bile Duct Tumor-Case Report and Literature Review.

Introduction: Sclerosing Extramedullary Hematopoietic Tumor (SEHT) is a very rare lesion associated with chronic myeloproliferative disorders (CMPD). SEHT can mimic morphologically, both macroscopically and microscopically, a wide variety of tumors/lesions. Case presentation: We present the case of a female patient diagnosed with gallstones for which surgery was decided. Intraoperatively, a malignant tumor of extrahepatic bile ducts was suspected. A frozen section examination raised the suspicion of a mesenchymal tumor or an inflammatory pseudotumor. The histological evaluation of the permanent sections, supplemented with an immunohistochemical investigation (IHC), was the one that established the diagnosis of SEHT, based on the presence of areas of sclerosis, atypical CD31+ megakaryocytes, myeloid and erythroid elements. Conclusions: The authors present the difficulties of a morphological diagnosis on the frozen section and on permanent sections in the absence of relevant clinical information and make a review of the literature data dedicated to the subject.

Unexpected diagnosis for a gastric polyp: Granular cell tumor: Case report and review of the literature.

A granular cell tumor (GCT) is a rare neoplasia that originates from Schwann cells. It usually appears in the skin or soft tissues, but it may occur anywhere in the body. The gastrointestinal tract is an unusual developmental site for a GCT, the esophagus being the most common site of origin for this tumor. The stomach is one of the most unique sites of origin for GCT, with less than 80 cases being mentioned in the literature. Histologically, GCTs consist of fusiform and polygonal cells, with granular cytoplasm, arranged in compact 'nests'. Immunohistochemically, these tumors show positivity for S100 protein, CD68, CD56 and, in a smaller percentage, they are positive for other antibodies, most notably inhibin alpha. We report the case of a 52-year-old woman with a solitary GCT that had developed in the gastric cardia, discovered on a routine gastroscopy and successfully treated by endoscopic submucosal dissection.

Prognostic significance of E-cadherin expression in hepatocellular carcinoma: correlations with clinical features.

BACKGROUND: Hepatocellular carcinoma (HCC) represents a major public health issue, being associated with high morbidity and mortality rates. Previous studies have demonstrated that reduction and∕or absence of E-cadherin expression is correlated with a potential for invasion and low survival rate in patients with HCC. PATIENTS, MATERIALS AND METHODS: We assessed the immunohistochemical expression of E-cadherin in 32 HCCs and peritumoral hepatic tissues using monoclonal anti-E-cadherin antibody (clone EP700Y), at 1:50 dilution, followed by incubation with Labeled Streptavidin-Biotin 2 (LSAB2) for 20 minutes, visualization of the reaction with 3,3'-Diaminobenzidine (DAB) and counterstaining with Mayer's Hematoxylin. RESULTS: The results we obtained show: an aberrant E-cadherin expression more frequent in dysplastic nodules (p=0.285) and in 81.25% of HCC cases, as compared to normal hepatic tissue (p<0.001); the absence of a statistically significant relationship between E-cadherin expression and patients' gender (p=0.854), tumor localization (p=0.429), associated viral infection [hepatitis B virus (HBV) or hepatitis C virus (HCV)] (p=0.513) or tumor size (p=0.788); the rate of positive E-cadherin expression was significantly higher in tumors with capsular infiltration (75%) (p=0.017) and does not appear to be influenced by vascular invasion (62.5%) (p=0.411), the presence of satellite nodules (p=0.285) or the serum level of alpha-fetoprotein (α-FP) (p=0.787). CONCLUSIONS: Reduced E-cadherin expression indicates a poor prognosis for patients with HCC and can be considered a potential predictive marker for the prognosis of these patients.