А case of a mucocele of the appendix - A diagnostic and therapeutic dilemma.

INTRODUCTION AND IMPORTANCE: Mucocele of the appendix is a rare pathology with an estimated incidence of less than 1 % of all appendectomies. Here is a report of a 67-year-old Bulgarian female, diagnosed with a low-grade appendiceal mucinous neoplasm (LAMN) after immunohistochemical analysis, which changed the therapeutic strategy. CASE PRESENTATION: We present a case of a patient, initially admitted to the Gastroenterology Department due to complaints of dyspepsia and intermittent watery diarrhea. Abdominal ultrasound revealed an oval hypoechoic heterogeneous formation with mixed echo structure in the ileocecal region. Laparoscopic appendectomy with partial cecal resection was performed. The additional immunohistochemical assessments classified the finding as a LAMN with 12 % proliferative index (Ki-67), pancreatin-positive reaction in epithelial cells and CD68-positive reaction in macrophages. CLINICAL DISCUSSION: Mucinous neoplasms of the appendix are classified on a spectrum from benign to malignant based upon certain features on histological examination. When there are signs of malignancy such as metastases in the loco-regional lymph nodes, perforation with intraperitoneal dissemination and affected base of the appendix (positive margins of resection), more aggressive approach is recommended - right hemicolectomy. Simple appendectomy is the choice for patients with benign mucocele as suggested by the presence of a normal caecum and appendicular base with no evidence of perforation. CONCLUSION: Appendiceal mucocele could be an illustrative example of a diagnostic and therapeutic challenge due to the rarity of the disease. Pathohistological examination and mainly immunohistochemical tests are the key to correct diagnosis and treatment.

Ruptured desmoid tumor imitating acute appendicitis - a rare reason for an emergency surgery.

BACKGROUND: Desmoid tumors, also known as aggressive fibromatosis, are extremely rare, accounting for less than 3% of soft-tissue sarcomas and less than 0,03% of all neoplasms. The diagnosis is usually delayed because of the lack of specific symptoms, and can sometimes lead to serious and, even fatal complications. CASE PRESENTATION: We report the case of a 27-year-old male patient presenting with the clinical picture of acute appendicitis. During the operation, we found a tumor in the jejunum with a necrotic zone and perforation on its surface, causing hemorrhagic effusion into the abdominal cavity and subsequent peritonitis. The tumor was removed with negative margins via resection of the small bowel. The final histological result showed aggressive fibromatosis. CONCLUSIONS: Aggressive fibromatosis remains a serious problem with the possibility of locally aggressive behavior with high rates of recurrence. Sometimes, its clinical and macroscopic recognition can be immensely tricky. As shown by our patient, on rare occasions, desmoid tumors can lead to acute surgical abdomen requiring an emergency operation.

Long-Term Survival and Complete Response to Anastrozole in Breast Cancer Patient With Cutaneous Metastases Only.

BACKGROUND/AIM: Metastatic breast cancer (MBC) represents a wide spectrum of heterogeneous conditions with different secondary spread sites, time to relapse and biology. MBC is still considered an incurable disease despite the fact that survival rates have improved in the last years. Cutaneous metastases are a rare site for metastatic spread and indicate advanced disease. The aim of this study is to demonstrate the excellent therapeutic result following endocrine therapy only in MBC with just skin involvement. CASE REPORT: We present a case of an 82-year-old woman with no family history of breast cancer (BC), who was diagnosed with de novo metastatic estrogen/progesterone receptor-positive and HER2-negative invasive lobular BC. The only site of secondary spread was the skin. She was treated with just endocrine therapy for 116 months with which she achieved and maintained long-term complete clinical response (CR). DISCUSSION: To our knowledge this is the only case of lobular BC with de novo metastatic manifestation as multiple skin metastases, which achieved CR following the aromatase inhibitor treatment (anastrozole) with such impressive long-term overall survival.

Combination of Juvenile Papillomatosis, Juvenile Fibroadenoma and Intraductal Carcinoma of the Breast in a 15-Year-old Girl.

UNLABELLED: The association of juvenile papillomatosis with carcinoma is proven, but very rare, as there exist several reported cases. CASE REPORT: A 15-year-old girl with no family history of breast cancer presented with two masses in the left breast. The excisional biopsy on both lumps revealed juvenile fibroadenoma and juvenile papillomatosis epithelial proliferation multiple cystic expanded channels. In some of these channels, cytological features of intraductal carcinoma were observed. We performed a full immunohistochemical examination of the juvenile papillomatosis. The patient refused any further surgical or adjuvant treatment. There are no signs of recurrence in the 15 year follow-up. DISCUSSION: This case is a diagnostic and therapeutic challenge, taking into account the patient's age and the controversial treatment recommendations. Good collaboration between surgeons and pathologists is essential for an accurate diagnostic process and aims to avoid under- or overtreatment.

Spectrum and frequencies of BRCA1/2 mutations in Bulgarian high risk breast cancer patients.

BACKGROUND: About 3885 women are diagnosed with breast cancer and 1285 die from the disease each year in Bulgaria. However no genetic testing to identify the mutations in high-risk families has been provided so far. METHODS: We evaluated 200 Bulgarian women with primary invasive breast cancer and with personal/ family history of breast cancer for the presence of unequivocally damaging germline mutations in BRCA1/2 using Sanger sequencing. RESULTS: Of the 200 patients, 39 (19.5 %) carried a disease predisposing mutation, including 28 (14 %) with a BRCA1 mutation and 11 (5.5 %) with a BRCA2 mutation. At BRCA1, 6 different mutations were identified, including 2 frameshifts, 1 nonsense and 1 missense that had been previously reported (c.5030_5033delCTAA, c.5263_5264insC, c.4603G > T, c.181 T > G), and 2 frameshifts, which were novel to this study (c.464delA, c.5397_5403delCCCTTGG). At BRCA2, 7 different frameshift mutations were identified, including 5 previously reported (5851_5854delAGTT, c.5946delT, c.5718_5719delCT, c.7910_7914delCCTTT,c.9098_9099insA) and 2 novel (c.8532_8533delAA, c.9682delA). A BRCA1 mutation was found in 18.4 % of women diagnosed with breast cancer at/or under the age of 40 compared to 11.2 % of women diagnosed at a later age; a BRCA2 mutation was found in 4 % of women diagnosed at/or under the age of 40 compared to 6.5 % of women diagnosed at a later age. A mutation was present in 26.8 % patients with a positive family history and in 14.4 % of women with a negative family history. The most prevalent mutation observed in 22 patients (11 %) was BRCA1 c.5263_5264insC, a known Slavic mutation with founder effect in Eastern European and AJ communities. Other recurrent mutations were BRCA2 c.9098-9099insA (2 %), BRCA1 c.181T > G (1 %) and BRCA2 c.5851_5854delAGTT (1 %). Notably, BRCA1 c.5263_5264insC represented 56 % of all mutations identified in this series. Of the 22 patients with BRCA1 c.5263_5264insC, 9 were diagnosed with early onset breast cancer, 11 with TNBCs, 4 with bilateral breast cancer, and 6 with both breast and ovarian cancer. CONCLUSIONS: This is the first comprehensive study of the BRCA1/2 mutation spectrum in Bulgaria and will assist the establishment of efficient protocols for genetic testing and individualized risk assessment for Bulgarian breast/ovarian cancer patients and healthy individuals at a high-risk.

Prognostic factors and indices in the complex treatment of ductal carcinoma in situ of the breast--review.

The ductal carcinoma in situ (DCIS) is the most rapidly growing subgroup in the family of the cancerous diseases of breast. The unclarified biology and pathogenesis of the DCIS result in uncertainty in the therapeutic measures, which leads to major variations in its treatment on a global scale. Contrary to the consensus reached for the complex therapeutic measures in the invasive carcinomas of the breast, the therapeutic strategy for the DCIS keeps on giving rise to lively discussions. The application of conservative surgery preserved the total survival rate achieved in patients with DCIS of the breast, however the high frequency of the local relapses remains an essential problem. The presented review of references aims attempting examinations of the following items: the studies on the therapeutic measures, and the application of prognostic systems for risk assessment of a relapse, which leads to individual approach in the choice of the most suitable combination of the therapeutic methods for patients with DCIS of the breast.

Simultaneous bilateral breast carcinomas: a category with frequent coexpression of HER-2 and ER-alpha, high Ki-67 and bcl-2, and low p53.

The aim of this study was to evaluate clinicopathological characteristics and immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and their axillary metastases. Immunohistochemical analysis and in situ hybridization were performed using formalin-fixed/paraffin-embedded tissues. In total, 15 primary and 9 metastatic tumors from 8 patients were evaluated. The expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), Ki 67, p53, bcl-2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was evaluated by chromogenic in situ hybridization (CISH). Four patients were younger that 40 years of age (mean 47 years). Six patients had pleomorphic lobular carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the contralateral breast. One patient had atypical medullary carcinoma in both breasts and 1 patient had atypical medullary carcinoma in 1 breast and pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors and corresponding metastatic tumors was similar for the expression of ER-alpha (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2 and ER-alpha is exceptional in hereditary breast carcinoma and sporadic breast carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression of HER-2 and ER-alpha. P53 protein expression was found in only 2/15 (13%) primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast carcinomas, which often express p53 protein. Most of the patients presented with axillary metastases and had very aggressive course. Characteristically, the tumors showed high levels of expression of ER-alpha and Her2 amplification, were bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical medullary carcinoma there was no expression of ER-alpha or amplification of Her-2.

Pilomatrix carcinoma with lymph node metastases.

Pilomatrix carcinoma is a rare skin tumor with an origin from hair matrix cells. The tumor is locally aggressive with a great tendency for recurrence, but the metastatic potential is limited. A pilomatrix carcinoma in 76-year-old female with lymph node metastases is presented. In addition to classical histopathological criteria and DNA ploidy analysis, a broad panel of antibodies was used for evaluation of the metastatic potential. Both primary tumor and lymph node metastasis revealed extremely high proliferation and apoptotic rates. High constant expressions of CD44v6 and P-cadherin were also observed. In the metastasis, significant reduction of E-cadherin and beta-catenin was detected. The best approach for assessment of metastatic potential of pilomatrix carcinoma seems to be the complex evaluation of routine histological criteria like vessel invasion, mitotic index, apoptotic count, and new molecular markers of cell death and adhesion.

Invasive lobular carcinoma in a hypoplastic breast.

Breast hypoplasia is encountered as part of genetic syndromes or as a result of iatrogenic factors. The incidence of this malformation and the occurrence of breast carcinoma in such cases are unknown. The authors present a 66-year-old patient with a severe breast hypoplasia and invasive lobular carcinoma. The advanced clinical stage required neoadjuvant chemotherapy. After 5 CMF cycles with no significant effect, a modified radical mastectomy with axillary lymph node dissection was performed. The pathological report revealed an infiltrating lobular carcinoma with combined classical and alveolar growth and with minor morphological changes after the chemotherapy. Immunostaining for cell proliferation markers, apoptotic regulators, and cell adhesion molecules, such as the CD44 family and members of the cadherin-catenin group, was performed. The tumor expressed a high bcl-2/low bax ratio and lacked p53 immunoreactivity, which could explain the resistance to neoajuvant therapy. The lack of adhesion molecules, except for strong E-cadherin and beta-catenin reactivity, and weak CD44v6 expression were demonstrated. To the authors' knowledge this is the first case of an invasive lobular carcinoma in a hypoplastic breast reported in the English literature.