Multivisceral Resection for Locally Advanced Gastric Cancer: A Systematic Review and Evidence Quality Assessment.

Patients with locally advanced gastric cancer (LAGC) often require multivisceral resection (MVR) of the involved organs to achieve R0 resection and local disease control. The aim of the present study was to systematically review all available literature on the postoperative and long-term outcomes of MVR for gastric cancer. The PubMed database was systematically searched by two independent investigators for studies concerning MVR for LAGC. In total, 30 original studies with 3362 patients met our inclusion criteria. R0 resection was achieved in 67.77% (95% CI, 65.75-69.73%) of patients. The spleen, colon and pancreas comprised the most frequently resected organs in the context of MVR. Pancreatic fistulae (10.08%, 95% CI, 7.99-12.63%), intraabdominal abscesses (9.92%, 95% CI, 7.85-12.46%) and anastomotic leaks (8.09%, 95% CI, 6.23-10.45%) constituted the most common postoperative complications. Using the available data, we estimated the mean 1-year survival at 62.2%, 3-year survival at 33.05%, and 5-year survival at 30.21% for the entire cohort. The survival rates were mainly correlated with lymphatic invasion, tumor size and patient age. Therefore, gastrectomy, together with MVR, is feasible and may offer a survival advantage compared to gastrectomy alone or no other surgical treatment in a selected group of patients. Consequently, both patient and tumor characteristics should be carefully assessed to optimize candidate selection.

Primary Synovial Sarcoma of the Kidney: Diagnostic Approach and Therapeutic Modalities for a Rare Nosological Entity.

Synovial sarcoma (SS) is a rare mesenchymal entity that represents 5-10% among soft tissue sarcomas (STS). Primary renal synovial sarcoma (PRSS) is an uncommon, rapidly growing tumor, with potential metastatic dissemination. The main prognostic factors of PRSS include tumor size and histologic grade, while translocation t (X; 18) (p11.2; q11.2) (fusion of SYT gene -chromosome 18- with SSX genes (1, 2 or 4)-chromosome X) is the most common pathognomonic sign. Aggressive surgical resection of the tumor along with concomitant regional lymphadenectomy is the treatment of choice for PRSS, while additional en bloc resection of the adjacent affected organs is often performed. To date, the role of preoperative or postoperative chemotherapy remains equivocal. The prognosis of patients with PRSS is poor, as the 5-year survival rate is only 20-30% and further deteriorates when a high mitotic activity is detected. Local recurrence even after complete R0 surgical excision remains the most frequent cause of death. The aim of this review was to meticulously discuss clinical features, histogenesis, and morphological and immunochemical findings of PRSS, while the role of current diagnostic and therapeutic management of this aggressive neoplasm was emphasized.

Metastatic malignant melanoma of the breast: report of a case and review of the literature.

Melanoma is the most rapidly increasing cancer in the world. Associated morbidity and mortality are mainly related to metastatic potential. Metastases to the breast from malignant melanoma are rare and represent only 1.3%-2.7% of reported cases. The aim of this study was to present a rare case of metastatic malignant melanoma to the breast. A 51-year-old woman was admitted for management of a palpable mass of the left breast. The past medical history referred to a sizable nodular melanoma that was removed from her back. Classification of the breast lesion was BI-RADS 5. Core needle biopsy was compatible with the diagnosis of malignant melanoma. Immunohistochemical evaluation was positive for Mart1 and Ki67. Subsequent staging was indicative of multiple secondary foci in the liver and bones. The patient was administered a combination of PD L1 inhibitor nivolumab with the anti-CTLA4 inhibitor ipilimumab followed by additional targeted therapy with the BRAF inhibitor vemurafenib. Metastasis to the breast from malignant melanoma is extremely rare. Nevertheless, breast metastases must be suspected in patients with a history of malignant melanoma. Moreover, recent breakthroughs in the Braf and MEK inhibitors and immune checkpoint inhibition therapies have impressively improved prognosis in patients affected by melanoma.

Evaluation of diagnostic algorithm and therapeutic interventions for intra-abdominal desmoid tumors.

Desmoid-type fibromatosis (DF) is a distinctly rare condition, mostly of younger adults, characterized by the development of locally aggressive tumors of mesenchymal origin. Desmoid tumors (DT) arise either sporadically or in association with FAP (familial adenomatous polyposis), although certain risk factors have also been identified, including pregnancy and antecedent surgical trauma. They can emerge from any connective tissue including muscle, fascia and aponeurosis and are therefore classified, according to location, as intra-abdominal, of the abdominal wall and extra-abdominal. Despite the lack of metastasizing potential, the course can be unpredictable. Various mutations of APC and ß-catenin genes, among others, play a catalytic role in the pathogenesis of this neoplastic entity. Surgery has lost its traditional role as first line treatment of the disease and several other treatment methods are being considered. Cytotoxic chemotherapy, non-cytotoxic systemic therapy and targeted therapy have been revealed as part of different treatment regimens. Recent progress regarding DT biology and molecular pathways has led to the development of promising novel biological agents. In any case, a multidisciplinary approach is required and is gradually employed, espe-cially in intra-abdominal DTs. In this review, we aim to present current knowledge on DF and summarize current treatment regimens as well as their effectiveness, with emphasis on the intraperitoneal type of DT.

The Impact of Nutritional and Functional Status on Postoperative Outcomes following Esophageal Cancer Surgery.

Malnourished patients undergoing esophagectomy have increased risk of postoperative complications. The aim of the current study was to identify nutritional and functional risk factors for postoperative complications in patients with esophageal and gastroesophageal junction cancer who underwent esophagectomy. Seventy patients who were admitted at the First Department of Surgery, Laikon General Hospital, Athens, Greece, were included in this study. Laboratory data and data regarding nutritional and functional status were recorded preoperatively. Postoperative complications were graded according to Clavien-Dindo classification. Thirty-seven patients (52.9%) developed postoperative complications. Albumin and Geriatric Nutritional Risk Index (GNRI) levels were lower in patients who developed major complications compared to patients who did not develop postoperative complications (3.90 ± 0.44 vs 4.18 ± 0.37 g/dL, p = 0.014 and 107.40 ± 15.76 vs 114.98 ± 12.26, p = 0.050 respectively). Major complications were associated with higher percentage of weight loss (12.1 ± 11.1 vs 6.2 ± 7.5%, p = 0.019) and with low handgrip strength (80 vs 16.9%, p = 0.006). Albumin (3.93 ± 0.18 vs 4.15 ± 0.41 g/dL, p = 0.019) and low muscle mass (22.6 vs 2.8%, p = 0.016) were significantly associated with anastomotic leakage occurence. The incorporation of patients' nutritional and functional status in the preoperative risk assessment might increase prognostic ability concerning postoperative complications of patients undergoing esophagectomy.

Career barriers for women in surgery.

BACKGROUND: Despite the increasing numbers of female medical students, surgery remains male-dominated. PURPOSE: To highlight the principal career obstacles experienced by aspiring female surgeons. METHODS: A narrative review of literature on the position and career barriers of female surgeons has been conducted, using the MEDLINE and EMBASE databases. MAIN FINDINGS: Implicit and even explicit biases against female surgeons remain prevalent, negatively impacting their training performance and overall professional trajectory. Female surgeons are globally underrepresented in leadership positions and senior academic rankings, especially that of a full professor. They feel hampered by lack of effective mentorship, whose value for a successful career has been acknowledged by all medical students, surgeons and surgical leaders. Their work-life imbalance is sometimes expressed as lower likelihood than their male contemporaries of getting married or having children and may be attributed to their conventional association with the role of caretaker, their personal desire to accommodate occupational and family duties and the inadequate implementation of parental leave and childcare policies. Female surgeons' "infertility" may be further explained by direct and indirect pregnancy-related difficulties. Female surgeons are also financially undercompensated compared to their male contemporaries. Finally, specialty-specific challenges should not be overlooked. CONCLUSIONS: While encouraging steps have been made, women in surgery feel still hindered by various obstacles. The qualitative, interview-based nature of current literature requires more meticulous studies on these barriers with a more quantitative and objective approach. Attenuation of gender imbalance in surgical specialties requires further changes in mentality and more targeted modifications in relevant policies.

Primary Squamous Cell Carcinoma of Colon and Rectum: A Systematic Review of the Literature.

Background - Objective: Primary colorectal squamous cell carcinoma is an extremely rare neoplasm with an incidence of 0.1 to 0.25 per 1,000 diagnosed colorectal carcinomas.The objective of this study was to evaluate its biological behavior and highlight the role of a surgical approach for its management.MethodsPubMed and Cohrane databases were independently searched (last search: April 10th, 2020) for articles concerning colorectal squamous cell carcinoma in adult population.Results: Seventy-one studies met predefined inclusion criteria and involved 99 patients (54.5% females) with an age of 56.98 ± 12.19 years (mean ± SD). The most frequent site of occurrence was the rectum (63.5%). Open surgery was conducted at 95% of patients, while 21.4% and 30.3% received neoadjuvant and adjuvant therapy respectively.Postoperative complications were developed in 31.3% of patients, while 6.1% died withing the first month following operation. Five-years survival rate was 49.5% (95% CI: 33.7%-63.4%). Female sex (HR: 0.24; 95% CI: 0.11-0.54; p-value: 0.001) and presence of postoperative complications (HR: 4.10; 95%CI: 1.47-1.46; p-value: 0.007) significantly affected the survival.Conclusions Colorectal Squamous Cell Carcinoma is a rare tumor with an aggressive behavior. Surgery is the standard of treatment for the colontumors, while the role of chemoradiotherapy is promising especially for rectal tumors. Further clinical trials are necessary to determine the preferred treatment approach.

Primary Angiosarcoma of the Gastrointestinal Tract: A Systematic Review of the Literature.

Primary Gastrointestinal Angiosarcoma (PGAS) constitutes a rare malignant tumor arising from vascular or lymphatic endothelial cells. The aim of this study was to review the available literature on PGAS and to elucidate its biological behavior and optimal therapeutic approach. PubMed and Embase bibliographical databases were systematically searched (last search April 8th, 2020) for studies concerning PGAS. Ninety-eight studies met our inclusion criteria, involving 110 patients (male/female = 1.5) with an age of 62.40 ± 17.84 (mean, SD) years. They were most frequently located at small (44.5%) and large intestine (35.5%), while 12.7% were multifocal. Surgical resection of the tumor was conducted at 84.0% of the cases combined with adjuvant therapy at 12.3%. One-year cumulative survival was 55.18% (95% CI: 34.33%-71.84%) for large intestine, 30.2% (95% CI: 17.1%-44.5%) for small intestine, whereas multifocal PGAS had a 6-months cumulative survival of 23.08% (95% CI: 5.58%-47.46%). Therefore, PGAS is an extremely rare entity with atypical clinical presentation, challenging diagnosis and aggressive behavior. High clinical suspicion is crucial for its prompt management. Further studies and the development of novel therapeutic agents are required in order to improve survival.

Epidemiology, diagnostic approach and therapeutic management of tailgut cysts: A systematic review.

BACKGROUND: Tailgut cysts (TGCs) are benign congenital abnormalities that usually present with non-specific symptoms, constituting a diagnostic dilemma for physicians. The aim of this study was to systematically review the literature concerning clinical manifestations, diagnostic modalities and histologic findings of TGCs and highlight current knowledge on therapeutic management of this rare entity. METHODS: PubMed and Embase databases were systematically searched by two independent investigators (last search 18 February 2021) for studies concerning TGCs published in the past two decades. RESULTS: Totally, 144 articles, including 135 case reports and 9 case series, met our inclusion criteria. One hundred eighty-four patients were included (3:1/female:male) with an age of 42.3 ± 18.7 years (mean, SD), while 5 cases concerned new-born infants. Pain was the prevailing clinical manifestation (41.8%), whereas 16.8% were asymptomatic. MRI and CT were utilized for diagnosis in 58.7% and 54.7% of cases, respectively. The majority of cysts were multilocular, while ciliated columnar epithelium and smooth muscles of the cyst wall were the prevailed histological findings. Malignant degeneration of TGCs was reported in 32.1% of cases, while carcinoid tumours were the most frequent malignancies. Surgical resection was performed in 155 cases, while laparoscopic and robotic approach was preferred in 18 and 2 cases, respectively. A posterior approach was implemented in 80.9%, anterior technique in 9% and combined technique in 6.7% of cases. Postoperative complications and recurrence of the cystic lesion were reported in 17.4% and 7.6% of cases, respectively. CONCLUSIONS: TGCs constitute a dilemma for the physicians. Surgical resection comprises the ultimate treatment to avoid complications or malignant transformation of the cyst. Concrete follow-up strategies and optimal therapeutic options should be outlined through consensus guidelines and at the time being, such decisions can be made only on the basis of extrapolation and on a case-by-case approach.

Evaluation of molecular and genetic predisposing parameters at diverticular disease of the colon.

BACKGROUND: Diverticular disease (DD) refers to the presence of diverticula throughout the gastrointestinal (GI) tract, mainly along colon. DD might evolve into diverticulitis that is accompanied by severe clinical presentation, which includes abscess formation, perforation, stricture, obstruction and/or fistula. AIM: The aim of the present review is to summarize the role of molecular and genetic factors in DD development, as well as their possible contribution towards new prognostic indicators, diagnostic algorithms and new therapeutic approaches. METHODS AND RESULTS: Except from common predisposing parameters, several genetic mutations, immune factors, neurotransmitters, hormones and protein dysfunctions have been associated to the early onset of DD symptoms, pathogenesis and prognosis of the disease. Specific structural changes in the colonic wall, altered matrix composition and compromised motility have been verified as possible pathogenic factors for the development of DD. Dysregulation in peristaltic activity and reduced ability of the longitudinal muscle to relax following contraction has been also associated with DD evolution. In addition, it has been suspected that genetic defects combined with alterations in intestinal microbiota might play an important role in diverticulitis presentation.

Clinical evidence, diagnostic approach and challenging therapeutic modalities for malignant melanoma of the anorectum.

Primary anorectal malignant melanoma (ARMM) is a rare, aggressive tumour that accounts for approximately 1.2% of all melanomas. This rare entity represents less than 5% of anorectal malignant tumours and 0.05-1% of all malignant colorectal neoplasms. The incidence increases with age while there is a higher prevalence in Caucasians. ARMM is often asymptomatic or presents with no disease-specific evidence so that it can mimic other rectal disorders, malignant or benign. Colonoscopy is obligatory as a diagnosing mean for ARMM. Furthermore, endoscopic ultrasonography, computed tomography and magnetic resonance imaging can be utilized for the evaluation of tumour infiltration and lymph node metastases. Moreover, diagnostic establishment of ARMM requires an undeniable demonstration of essential melanocytic features in histology and immunohistochemistry. Even though the standard of treatment remains surgical resection, the choice between wide local excision and abdomino-perineal resection is still controversial. Recently, there have been recommendations regarding new techniques which could be utilized for the surgical treatment of ARMM. Newer treatments that have been proposed such as immune-checkpoint inhibitors and targeted therapies need further validation. A multicenter study would allow clarification of the most appropriate therapeutic strategy for this uncommon nosological entity.

Clinicopathological Data and Treatment Modalities for Pancreatic Somatostatinomas.

BACKGROUND/AIM: Somatostatinomas (SSomas) constitute a rare neuroendocrine tumor. The purpose of this study was to evaluate the current published literature about pancreatic SSomas and report epidemiologic and clinicopathologic data for this entity. PATIENTS AND METHODS: A combined automated and manual systematic database search of the literature was performed using electronic search engines (Medline PubMed, Scopus, Ovid and Cochrane Library), until February 2020. Statistical analysis was performed using the R language and environment for statistical computing. RESULTS: Overall, the research revealed a total of 36 pancreatic SSoma cases. Patient mean age was 50.25 years. The most common pancreatic location was the pancreatic head (61.8%). The most frequent clinical symptom was abdominal pain (61.1%). Diagnostic algorithm most often included Computed Tomography and biopsy; surgical resection was performed in 28 cases. Out of the 36 cases, 22 had been diagnosed with a metastatic tumor and metastasectomy was performed in 6 patients with a worse overall survival (OS) (p=0.029). In total, OS was 47.74 months. CONCLUSION: Patients with metastatic disease did not benefit from metastasectomy, but the sample size was small to reach definite conclusions. However, further studies with longer follow-up are needed for a better evaluation of these results.

Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review.

Cancer is a medical condition which has a molecular basis. Proto-oncogenes are the first regulatory factors of this biological process. They act in transmitting signals, resulting as growth factors. Modifications of these genes, called oncogenes, lead to the appearance of cancer cells. The activation process leading to proto-oncogenes are chromosomal translocation, point mutation, and gene amplification. Concerning the clonal theory of oncogenesis, it is believed that a tumor starts from a cell. Furthermore, there is close association between tumor development and inhibition of apoptosis or programmed cell death, providing cell immortality. Angiogenesis and angiogenic factors found to be expressed in tumors and may play a key role in tumor formation and development. Tumor-suppressor genes block the growth of cancer and contribute to the normal development of cells. This article highlights the evidence that neoplasms develop as the after-effect of the increase of acquired and physical genetic variations in proto-oncogenes and tumor-suppressor genes; these form a target group in the cells of neoplasms. Tumor formation and development are characterized by individual processes, working synergistically, and an understanding of each individual process may provide a better basis for further anticancer research.

Prone position thoracoscopic management of neck chyle leak following major head and neck surgery. A case series.

Chyle leak is a major compication following head and neck surgery, with reported incidence of 0.5% up to 8.3% in published literature. Cervical chyle leak may be challenging to manage with significant morbidity, resulting from extensive fluid and nutritional losses. This manuscript presents four cases of cervical chyle leak after head and neck surgery. Cervical thoracic duct injury had been identified intra-operatively. Conservative treatment failed to reduce chylous output post-operatively. All patients were offered thoracocscopic thoracic duct ligation in prone position; thoracic duct was dissected above the right diaphragm and ligated. Immediate resolution of their symptoms followed, with no recurrence at the follow-up period. Intra-operative repair of cervical thoracic duct remains controversial, while when identified early reduces the following comorbidities. Conservative management addresses reduction of chylous output, while amplifying hydration and alimentation. Thoracoscopic thoracic duct ligation offers a safe and feasible treatment for cervival chyle leak following head and neck surgery with all the advances of minimally-invasive surgery. KEY WORDS: Chyle leak, Head and Neck Surgery, Thoracoscopic, Thorasic Duct, Ligation, Minimally-Invasive.

Supravesical hernias: a systematic review of the literature.

BACKGROUND: A supravesical hernia (SH) is a rare abdominal wall hernia that is defined by the protrusion of abdominal viscera through the supravesical fossa. The objective of this study was to review current literature on SHs and elucidate their clinical manifestations and preferred therapeutic approach. METHODS: PubMed, Embase and Cochrane bibliographical databases were searched (last search: 30 March 2020) for articles reporting on SHs. RESULTS: Thirty-four studies met our inclusion criteria and involved collectively 38 patients (94.7% males) with an age of 59.57 ± 14.84 (mean ± standard deviation) years. Abdominal pain (81.6%) and nausea and vomit (71.1%) were the most frequently encountered symptoms. The majority of patients (78.1%) had signs of bowel obstruction. Twenty-nine patients (76.3%) suffered from an internal SH, while nine (23.7%) had an external one. An open hernia repair was conducted at 29 patients (76.3%), while eight (21.1%) had a laparoscopic approach and in one case (2.6%) the laparoscopic operation was converted to an open one. A mesh was applied at 14.3% of included cases. Eight patients (21.1%) underwent a bowel resection and hernia sac was resected at six (15.8%) cases. Four patients (11.8%) experienced postoperative complications and one patient (2.9%) died on first postoperative day. CONCLUSION: SH is an extremely rare type of hernia occurring through the supravesical fossa between the remnants of urachus and foetal umbilical arteries. All clinicians should be aware of this entity and further studies are necessary in order to clarify their aetiology, true incidence and optimal therapeutic approach.

Combined hepatocellular-cholangiocarcinoma: An update on epidemiology, classification, diagnosis and management.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare subtype of primary hepatic malignancies, with variably reported incidence between 0.4%-14.2% of primary liver cancer cases. This study aimed to systematically review the epidemiological, clinicopathological, diagnostic and therapeutic data for this rare entity. DATA SOURCES: We reviewed the literature of diagnostic approach of CHC with special reference to its clinical, molecular and histopathological characteristics. Additional analysis of the recent literature in order to evaluate the results of surgical and systemic treatment of this entity has been accomplished. RESULTS: The median age at CHC's diagnosis appears to be between 50 and 75 years. Evaluation of tumor markers [alpha fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)] along with imaging patterns provides better opportunities for CHC's preoperative diagnosis. Reported clinicopathologic prognostic parameters possibly correlated with increased tumor recurrence and grimmer survival odds include advanced age, tumor size, nodal and distal metastases, vascular and regional organ invasion, multifocality, decreased capsule formation, stem-cell features verification and increased GGT as well as CA19-9 and CEA levels. In case of inoperable or recurrent disease, combinations of cholangiocarcinoma-directed systemic agents display superior results over sorafenib. Liver-directed methods, such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), hepatic arterial infusion chemotherapy (HAIC), radioembolization and ablative therapies, demonstrate inferior efficacy than in cases of hepatocellular carcinoma (HCC) due to CHC's common hypovascularity. CONCLUSIONS: CHC demonstrates an overlapping clinical and biological pattern between its malignant ingredients. Natural history of the disease seems to be determined by the predominant tumor element. Gold standard for diagnosis is histology of surgical specimens. Regarding therapeutic interventions, major hepatectomy is acknowledged as the cornerstone of treatment whereas minor hepatectomy and liver transplantation may be applied in patients with advanced cirrhosis. Despite all therapeutic attempts, prognosis of CHC remains dismal.

Human Papilloma Virus infection and breast cancer development: Challenging theories and controversies with regard to their potential association.

Breast cancer (BC) remains the most frequently diagnosed malignancy among women worldwide. Recognized predisposing factors may be absent in the majority of affected patients, which has aroused a stronger interest in identifying risk parameters that contribute to BC pathogenesis. Human papilloma virus (HPV) infection is strongly associated with malignancies, such as cervical cancer, oropharyngeal cancer and anal cancer. Various surveys have linked HPV to the development of BC. Relevant variations in HPV identification among BC samples may be attributed to differences in study design, the populations involved and the HPV detection techniques applied, which are still controversial with conflicting opinions and results that deny the causative association between HPV infection and BC development. Furthermore, the role of HPV, a potential cause of human BC, has recently received more attention because of the possible restriction of disease progression using an HPV vaccine. The aim of this review was to evaluate both the aspects supporting and those against the theory of BC related to HPV infection. Recent literature has been also assessed in order to provide an update on the current concepts of relevant association.

Assessment of Synergistic Contribution of Histone Deacetylases in Prognosis and Therapeutic Management of Sarcoma.

Sarcomas are a rare group of neoplasms with a mesenchymal origin that are mainly characterized by the abnormal growth of connective tissue cells. The standard treatment for local control of sarcomas includes surgery and radiation, while for adjuvant and palliative therapy, chemotherapy has been strongly recommended. Despite the availability of multimodal therapies, the survival rate for patients with sarcoma is still not satisfactory. In recent decades, there has been a considerable effort to overcome chemotherapy resistance in sarcoma cells. This has led to the investigation of more cellular compounds implicated in gene expression and transcription processes. Furthermore, it has been discovered that histone acetylation/deacetylation equilibrium is affected in carcinogenesis, leading to a modified chromatin structure and therefore changes in gene expression. In addition, histone deacetylase inhibition is found to play a key role in limiting the tumor burden in sarcomas, as histone deacetylase inhibitors act on well-described oncogenic signaling pathways. Histone deacetylase inhibitors disrupt the increased cell motility and invasiveness of sarcoma cells, undermining their metastatic potential. Moreover, their activity on evoking cell arrest has been extensively described, with histone deacetylase inhibitors regulating the reactivation of tumor suppressor genes and induction of apoptosis. Promoting autophagy and increasing cellular reactive oxygen species are also included in the antitumor activity of histone deacetylase inhibitors. It should be noted that many studies revealed the synergy between histone deacetylase inhibitors and other drugs, leading to the enhancement of an antitumor effect in sarcomas. Therefore, there is an urgent need for therapeutic interventions modulated according to the distinct clinical and molecular characteristics of each sarcoma subtype. It is concluded that a better understanding of histone deacetylase and histone deacetylase inhibitors could provide patients with sarcoma with more targeted and efficient therapies, which may contribute to significant improvement of their survival potential.

Malignant melanoma of the breast: controversies in the diagnosis and therapeutic management of a rare nosologic entity.

Melanoma of the breast is an infrequent entity, presenting as either primary or metastatic from extramammary solid neoplasms. Depending on the involvement of the skin, primary malignant melanoma of the breast (PMMB) can be classified as cutaneous or noncutaneous. Cutaneous PMMB accounts for <5% of all melanomas and only 0.5% of all breast cancers. Furthermore, despite the rarity of metastatic breast neoplasms, melanoma comprises a frequent source of metastases. Metastatic potential of melanoma is associated with poor prognosis, and the majority of patients present more than one metastatic foci at the time of diagnosis. Diagnostic approach for both primary and metastatic melanomas of the breast is substantiated by fine needle aspiration (FNA) cytology along with immunohistochemistry. Nevertheless, verification of a metastatic mammary melanoma requires the discovery of a primary lesion. The mainstay of treatment for primary tumors is surgery, with radical local excision and axillary lymph node dissection or, on occasion, axillary sentinel node resection, while for metastatic tumors it depends on the specificities of the melanoma. Adjuvant therapy is always implemented. The aim of this survey is to meticulously review the literature of primary and metastatic malignant melanomas of the breast and report epidemiologic and clinicopathologic data for this rare entity. Clinical features, histogenesis, morphological, and immunochemical findings are discussed, while the role of current diagnostic and therapeutic management of this uncommon entity is emphasized.