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.

Carcinomatous-like mastitis due to axillary lymphadenopathy in a case of nasopharyngeal carcinoma: A case report.

Nasopharyngeal carcinoma (NPC) is a rare form of malignancy, accounting for 2% of all cancers of the head and neck in Europe. Axillary lymph node metastases are very rare in these cases. This is a case report of a 40-year-old premenopausal woman diagnosed in May 2015 with T1N2M0 stage III NPC, treated with induction chemotherapy, followed by chemo-radiotherapy. Post-therapeutic computed tomography (CT) scan showed partial response (PR) on the primary tumor and complete response (CR) on the latero-cervical lymph nodes. In 2017, our patient developed left carcinomatous-like mastitis with axillary lymphadenopathy. This raised suspicions of a carcinomatous mastitis. The pathology report with immunohistochemistry (IHC) of the third biopsy highlighted axillary metastasis of a non-keratinizing squamous cell carcinoma (NSCC). There are very few references in the literature regarding axillary metastases from squamous cell carcinoma of the head and neck (HNSCC). As far as we know, this is the first case report of mastitis due to NPC. To conclude, treatment consisted of two surgical excisions of axillary lymphadenopathy associated with local radiotherapy and chemotherapy (neo-adjuvant, adjuvant). The second surgery, performed after radiotherapy, required plastic surgery. A psychiatric evaluation was necessary, revealing a reactive anxiety disorder. This case required multidisciplinary management, where oncology, plastic surgery, pathology and psychiatric specialists collaborated in deciding the therapeutic approach.

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.

Prostate carcinomas mimicking a digestive malignancy.

AIM: To report our experience with specific cases of prostate cancer (PC) in which patients presented digestive symptoms, cases that represent a challenge and a source of error regarding the clinical and morphological diagnosis. METHODS: The most important clinical and pathological data were collected from three patients with PC which presented symptoms and/or investigations that initially suggested a digestive malignant tumor. RESULTS: We identified three patients with PC where the prostate tumor was not suspected based on the clinical-imagistic data, the correct diagnosis being the prerogative of the morphological investigation: in the first case, PC was detected during the microscopic examination of the lymph nodes (LN) in the intestinal resection specimen performed for suspected rectal cancer (RC), in the second case, in which the PC was synchronous with a RC, the dominant symptomatology was gastrointestinal, and in the third case, initially, the patient presented a widely disseminated PC, with pleural and bone metastases, as well as LN metastases, and apparent peritoneal involvement. CONCLUSIONS: Unusual forms of PC presentation are not as rare as expected and should be acknowledged by all those involved in diagnosing this neoplasm. PC should always be considered in the differential diagnosis of a rectal tumor. The immunohistochemical (IHC) investigation is essential for establishing the diagnosis in difficult cases. An integrated approach of the interpretation of clinical manifestations, imagistic and serological changes would shorten the diagnostic time and help reduce diagnostic errors.

Paving the way to tumor budding assessment using digital pathology: a pilot study in Timisoara City (Romania).

BACKGROUND AND AIM: The outcome for some colorectal cancer patients correlates poorly with classical prognostic factors, like tumor stage. Tumor budding (TB) is a promising and intensely studied new prognostic factor. We aimed to evaluate the reliability of bud counting on Hematoxylin-Eosin (HE)-stained and immunohistochemically (IHC)-stained scanned slides. MATERIALS AND METHODS: We evaluated 21 cases of robotic surgery colorectal cancer specimens that were submitted to the Department of Pathology, Emergency County Hospital, Timisoara, Romania. TB was assessed by one experienced (R3) and two junior pathologists (R1, R2), in 10 circular areas at 20× (0.785 mm²) on scanned HE-stained and IHC-stained [cytokeratin (CK) AE1∕AE3] slides. Interobserver agreement (Cohen's kappa) and intraclass correlation coefficient (ICC) were calculated. RESULTS: In the case of HE-stained slides, the inter-item correlation matrix showed values between 0.632 and 0.84, while the ICC on average measures for consistency showed very good correlation [ICC: 0.887, 95% confidence interval (CI): 0.765-0.95)]. The inter-item correlation matrix for IHC-stained slides comprised values between 0.864 and 0.921, while the ICC for average measures for consistency yielded an excellent value (ICC: 0.95, 95% CI: 0.896-0.978). We identified higher values for budding scores on IHC-stained slides, in comparison to the HE-stained slides: in 19∕21 cases for R1 (average increase of 234.85%), 16∕21 cases for R2 (average increase of 114.14%), and 20∕21 cases for R3 (average increase of 66.92%). CONCLUSIONS: We consider the method of buds counting in 10 microscopic fields on scanned slides to be reliable and valuable. TB counts are higher on IHC-stained slides and associate a better interobserver agreement.

In vivo confocal microscopy quantification of reactive oxygen species: a working model in rat kidney.

Oxidative stress is a culprit responsible for the development of acute and chronic kidney diseases. We aimed to establish a working model for the dynamic in vivo assessment of reactive oxygen species (ROS) production in rat kidney. A randomized controlled study was performed in 36 adult male Wistar rats subjected to unilateral urinary obstruction (UUO) via ureteral ligation and compared to SHAM controls. Dihydroethidium (DHE) was injected in the femoral vein and in vivo confocal microscopy was performed in the 2nd, 6th and 10th day, respectively after surgery. Maximal ROS levels elicited by UUO were recorded on the 6th day. However, the absolute difference of the means of DHE fluorescence intensity between UUO and SHAM was the highest on the 10th day. Our working model can monitor ROS production at different time frames and our initial findings suggest that the surgery-related ROS levels decline after an initial increase in the first days, whereas the ones elicited by chronic ligation continue to raise.

Surgical treatment in a case of giant macrodystrophia lipomatosa of the forefoot.

Macrodystrophia lipomatosa is a rare, congenital, non-hereditary disease, characterized by local gigantism of the fingers or toes. We report the case of a 37-month-old boy, with no prior past medical history, who presented with a gigantic dystrophy of the left forefoot. The location of the deformity was involving the plantar and dorsal aspect of the foot, and digits 1 to 4. After clinical examination, imaging study assessment, and differential diagnosis considerations, it was established that macrodystrophia lipomatosa was the cause of the deformity. A reconstructive surgical intervention was planned. The hypertrophied tissues were excised, resulting in a reduction in the forefoot's volume. The patient had a favorable postoperative course and ambulation was allowed with a custom-made shoe. The case represents a rare pathological entity with complex diagnostic and therapeutic considerations. As far as treatment options, the surgeon must decide between a reconstructive surgical intervention and amputation.