Primary Melanoma Histopathologic Predictors of Sentinel Lymph Node Positivity: A Proposed Scoring System for Risk Assessment and Patient Selection in a Clinical Setting.

Background and Objectives: The careful selection of adequate SLNB candidates not only aims at reducing the surgical risk while identifying SLN metastasis, but also plays a crucial role in identifying the patients eligible for adjuvant therapy. Objectives: The purpose of our study was to investigate the clinical and histologic aspects of primary melanomas that correlate with the likelihood of a positive SLNB result. Materials and Methods: A total of 101 primary melanoma patients who underwent sentinel lymph node biopsies were included in the study. General patient demographics were obtained as well as localization and melanoma-specific characteristics of primary melanoma from histologic reports in addition to data derived from SLNB melanoma histopathology reports. Results: The patients with positive SLN results had a statistically significant increased Breslow thickness (3.8 mm vs. 1.97 mm, p = 0.002), higher mitotic index rate (5/mm2 vs. 2/mm2, p = 0.009), as well as the presence of ulceration (68.4% vs. 31.6%, p = 0.007). Univariate regression analysis showed the Breslow thickness (p = 0.008), the mitotic index rate (p = 0.054), the presence of ulceration (p = 0.009), as well as the pT3-4 stage (p = 0.009) to be significant predictors of SLN positivity. The optimal cut-off values for Breslow thickness and the number of mitoses scores were determined based on ROC curve analysis. Using the Breslow thickness, mitotic index rate, presence of ulceration, and pT3-4 stage significant coefficients from the univariate regression model, a chance prediction score was developed. Conclusions: The newly developed and proposed scoring system can aid in patient selection for SLN biopsy by facilitating a more efficient risk assessment in the detection of lymph node metastases in melanoma patients.

Goblet cell carcinoid of the appendix. Review of the literature a propos of a rare case of endometrial metastases.

BACKGROUND: Carcinoid tumors are rare tumors most commonly found in the gastrointestinal tract. They represent the most common malignancies of the appendix. As a distinct entity from both adenocarcinomas and carcinoids, Goblet cell carcinoid (GCC) was initially described in the literature in 1969. The GCC is almost exclusive to the appendix, but rarely can be found in rectum, ileum and colon. More than 50% of the patients at the time of diagnosis already have advancedstage disease. The most common metastatic sites are the peritoneal surfaces of the pelvis and abdominal cavity, and ovaries in women. Surgery is the main form of treatment in patients with GCC. CASE PRESENTATION: A 49-year-old woman was treated at the Institute of Oncology and Radiology of Serbia with histopathological findings of GCC. In a 8-year period the patient was treated with initial appendectomy and three more operations because of locoregional disease progression. The last operation was performed in March 2016 because of endometrial metastases. Since then the patient is on regular follow up without disease progression. CONCLUSION: GCC is a very rare entity. Multidisciplinary approach is necessary for adequate patient treatment.

Multifocality as independent prognostic factor in papillary thyroid cancer - A multivariate analysis.

PURPOSE: The incidence of multifocality of papillary thyroid carcinoma (PTC) ranges from 18 to 87.5% The mechanisms of multifocal spreading, correlation with tumor size, histology variants of PTC, lymph node metastases, and prognostic impact remains unclear. The purpose of this study was to clarify the prognostic significance of multifocality on relapse and survival rates of patients with PTC by analyzing the correlation of multifocality with patient age, gender, tumor size, histological variants of PTC, presence of lymph node metastases and extent of surgery. METHODS: 153 patients with PTC were included in this study. Patients with pT4 tumors or initially distant metastases were excluded from study. Total thyroidectomy was done in all 153 patients. Central and level III and IV lateral neck lymph node dissection was done in 76.5% of the patients, followed by modified radical neck dissection if positive. RESULTS: Multifocality was found in 43 (28%) whole thyroid gland specimens, and was significantly more frequent in patients older than 45 years and in tumors greater than 4 cm in diameter (p<0.01). Presence of multifocality didn't significantly correlate with gender, histology variants of PTC or lymph node metastases. In a median follow up of 84 months locoregional relapse occurred in 8.4% and 1.3% of the patients, while 7.2% patients died due to PTC. The incidence of relapse was significantly higher (p<0.01), and relapse free interval and survival were significantly shorter (p=0.0095, p=0.0004, respectively) in patients with multifocal PTC. Cox multivariate regression analysis showed that multifocality was independent prognostic factor for both disease-free interval (DFI) and cancer-specific survival (CSS) of patients with PTC. CONCLUSION: Due to high incidence of multifocality and potential prognostic impact, total thyroidectomy should be advocated in all patients with PTC, aiming to reduce relapse rate and improve DFI and CSS.

Prognostic importance of steroid receptor status for disease free and overall survival after surgical resection of isolated liver metastasis in breast cancer patients.

PURPOSE: Breast cancer (BC) is the most common malignancy among women, while isolated operable liver metastases (LMs) from BC are very rare and occur in only 1-5% of the patients. Besides, positive steroid receptor (SR) status for oestrogen and/or progesterone is known as a factor which improves disease free survival (DFS) and overall survival (OS). The primary aim of this study was to examine the impact of SR status on DFS and OS after liver metastasectomy in female patients with primary BC. METHODS: We analyzed 32 medical records of female patients diagnosed and treated for primary BC with LMS as the first and only site of disease progression, at the Institute of Oncology and Radiology of Serbia (IORS), during 2006- 2009. All of them underwent primary BC surgery as well as LMs resection. RESULTS: Patients with metachronous BC and LMs and positive SR status in both BC and LM (BC+/LM+) had a median time from BC to LM occurrence (TTLM) of 36 months, compared to BC+/LM- and BC-/LM- subgroups, whose medians for TTLM were 30.5 and 14.5 months, respectively (p<0.01). For all patients, positive SR status showed high correlation with longer DFS and OS after LM resection (medians according survival analysis for DFS/OS in subgroups BC-/LM-, BC+/LM- and BC+-LM+ were 10/19, 25/45, 50/not reached months respectively; p<0.01 for DFS/ OS). Cox regression analysis confirmed that the subgroup of patients with BC-/LM- had 10.8 and 18.8 higher risk of events for DFS (disease relapse or death) and event for OS (death only), respectively, compared to BC+/LM+ subgroup of patients. CONCLUSION: Positive SR status in BC and LM has a high impact not only on time from BC to LM occurrence, but also on longer DFS and OS after LM resection.

The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors.

PURPOSE: This article examines as to whether the Ki-67 index may be useful as a marker for cell proliferation, as well as to whether Ki-67 immunohistochemical expression and parathyroid hormone (PTH) levels are useful in distinguishing between parathyroid carcinoma (PC) and adenoma. METHODS: A retrospective analysis of 50 patients (10 with PC and 40 with adenoma) who had been previously diagnosed with primary hyperparathyroidism (PHPT) was conducted. Normal parathyroid glands served as the control group. Immunostaining of Ki-67 was estimated through image analysis and the results were statistically analyzed. RESULTS: Ki-67 was higher in PC patients (median 785.15) compared to adenoma patients (median 297.41; Mann-Whitney U-test p<0.001). ROC analysis confirmed that Ki-67 has a positive predictive marker in diagnosing cancer. Mann-Whitney U-test confirmed a highly statistically significant difference in the preoperative PTH levels between the PC and adenoma group (p <0.001). The PTH serum preoperative level was higher in PC patients (median 1721) than in those with adenoma (median 189.5). A highly significant correlation was also found between Ki-67 and preoperative PTH levels (p <0.001). CONCLUSION: A higher rate of cellular proliferation was noted in malignant tumors as compared to benign tumors. Moreover, the expression profile of Ki-67 and high PTH levels in this study indicates a role for them as potential markers of malignancy.

Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information.

BACKGROUND: The St. Gallen International Expert Consensus of 2011 proposes a new classification system for breast cancer based on its division into five subgroups. The criteria to identify these subtypes were recently refined at the 2013 Conference. In this respect, the authors of this paper have conducted a retrospective analysis of breast cancer subtypes, related to Ki-67 and involvement of the axillary lymph nodes (ALNs). The analysis was performed only in the cases of invasive breast cancer in the pT2 stages. The research and results of the paper have shown that investigating the value of these parameters could be of great benefit in future treatment strategies of invasive breast cancer. METHODS: A retrospective analysis of breast cancer subtypes, tumor nodal metastatic staging, and histopathological grading of 108 cases has been performed according to the methods recommended and provided by the St. Gallen International Expert Consensus Report, 2011. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 of 108 tumor samples were all investigated by immunohistochemistry according to the methods used to classify breast cancer subtypes as proposed in the St. Gallen Consensus Report, 2011. Invasive breast cancers (n = 108) were immunohistochemically classified as follows: 28 (25.92%) as Luminal A, 51 (47.22%) as Luminal B (HER2 negative), 21 (19.44%) as Luminal B-like (HER2 negative), 2 (1.85%) as HER2 positive, and 6 (5.55%) as being a triple-negative subtype. RESULTS: The conclusion was made that when Ki-67 was found to be higher, patients also showed a higher involvement in their ALNs. The chi-square test shows the difference to be significant (chi-square = 4.757; P = 0.029). Luminal B subtypes had the highest percentage (54.9%) of involvement of lymph nodes when compared to the other four subtypes. The Luminal B subtype had a higher percentage (51.4%) of involvement of lymph nodes than did Luminal A (10.7%). The chi-square test also shows the difference to be significant (P < 0.05). CONCLUSION: A combination of the Ki-67 index, HER negative tumors, PR negativity, and a low value that can be used to segregate ER positive pT2 tumors into prognostically significantly different clinical outcomes may be utilized clinically to guide patient management in accordance with these tumor characteristics.

Three Cases of Combined Therapy in Primary Breast Lymphoma (PBL) with Successful Outcomes.

Primary malignant lymphoma of the breast is a rare tumor, defined as a tumor localized in the breast with or without axillary lymph-node metastases. Such a tumor is mainly found in female patients and located more frequently in the right breast. It is difficult to make primary breast lymphoma (PBL) diagnosis before operation, and PBL diagnosis is mainly based on pathological biopsy and immunohistochemical staining. In this paper, the cases of three patients who had PBL, and who were treated for it at the Institute for Oncology and Radiology of Serbia between 2008 and 2012, are reviewed and discussed. These cases of PBL had no recorded reoccurrence of the disease and were originally treated by surgery, radiotherapy R-CHOP, and/or chemotherapy. While there is no consensus to the question of how to best treat PBL (ie, with chemotherapy, radiotherapy, or combined therapy), it is hoped that this review will offer insight into successful treatment procedures for tumors of this category.