Locally advanced cervical rhabdomyosarcoma in adults: A case report.

BACKGROUND: Rhabdomyosarcoma is a soft tissue tumor of primitive mesenchymal cells origin, occurring predominantly in children and adolescents, but extremely rare in adults and the data regarding its treatment are sparse. Here, we would like to share our experience in the treatment of a locally advanced primary embryonal rhabdomyosarcoma of cervix in a 39-year-old female. CASE SUMMARY: The patient was admitted with symptoms of intermenstrual bleeding and postcoital bleeding for six months. Physical examination revealed a friable, polyp-like mass (5 cm × 5 cm) in her cervix protruding into the vagina, while the uterus was mobile and normal-sized. Colposcopy-directed biopsy was performed, and a pathological diagnosis of embryonal rhabdomyosarcoma was made. Magnetic resonance imaging of the pelvis showed that the cervical volume was significantly increased, with a hypointense and hyperintense soft tissue mass on the right side, invading the cervical stroma; the mass was 5 cm × 5 cm with a clear boundary and confined to the cervix; there were no obvious findings indicating tumor invasion in the vaginal wall, parametrium, or pelvic wall; no enlarged lymph nodes were observed in the pelvic cavity. Based on our findings, the tumor was classified as stage IA according to the intergroup rhabdomyosarcoma studies criteria and IB3 stage according to The International Federation of Gynecology and Obstetrics 2018. The patient underwent two courses of neoadjuvant chemotherapy and a partial remission was achieved. Subsequently, she underwent laparoscopic radical hysterectomy, bilateral salpingo-oophrectomy and pelvic lymph node dissection and there were no risk factors revealed by postoperative pathological examination. Adjuvant chemotherapy was performed after surgery. The patient was disease-free until the last follow-up, 49 mo after completing the entire treatment. CONCLUSION: Our experience suggests that neoadjuvant vincristine, dactinomycin, and cyclophosphamide chemotherapy followed by radical surgery and adjuvant chemotherapy might be reasonable therapeutic option for bulky cervical rhabdomyosarcoma in adults without fertility desire. Since large-scale studies on such rare conditions are rather impossible, further case reports and systematic reviews could help optimize the treatment of primary, bulky cervical rhabdomyosarcoma in adults.

Follow-up Study on the Outcomes of Recovered Pregnant Women with a History of COVID-19 in the First and Second Trimesters: A Case Series from China.

OBJECTIVE: To determine the pregnancy and neonatal outcomes of women who recovered from coronavirus disease 2019 (COVID-19) that developed in early pregnancy. METHODS: This case series analyzed five pregnant women (26-33 years) whom recovered from COVID-19 which were developed in early pregnancy (6-27 weeks) and admitted at the Wuhan Union Hospital from January 15, 2020 to April 30, 2020. The clinical manifestation, laboratory examinations, treatment, pregnancy outcomes, maternal and neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throat swab reverse transcription polymerase chain reaction test results, and SARS-CoV-2 antibody test results in neonates were reviewed. The placental pathology, placental angiotensin-converting enzyme 2 expression were studied by hematoxylin-eosin and immunohistochemistry staining, SARS-CoV-2 presence was examined by QT-PCR. We also followed up the infants at 3-6 months. RESULTS: Three pregnant women were diagnosed with COVID-19 in early pregnancy (Cases 1-3), and two were serum immunoglobulin G positive asymptomatic cases (Cases 4 and 5). Cases 1-3 showed complete recovery after severe COVID-19. Case 3 was infected at 6 weeks of gestation during the first trimester and had induced medical abortion at 12 weeks of gestation. All neonates had no pneumonia, SARS-CoV-2 mRNA reverse transcription polymerase chain reaction and serum immunoglobulin M were negative, and immunoglobulin G were positive. All placental samples were negative for SARS-CoV-2 in the nucleic acid test. Placental pathology showed chronic ischemia changes. ACE-2 expressed in both placenta and decidua. The follow-up showed that the infants were healthy and asymptomatic at 3-6 months. CONCLUSION: No adverse outcomes was observed in our case series. However, systemic inflammatory responses to SARS-CoV-2 infection may cause placental injury. At the time of delivery after recovery from COVID-19, no SARS-CoV-2 positive results was found in the placenta in this case series.

Region-specific Risk Factors for Pelvic Lymph Node Metastasis in Patients with Stage IB1 Cervical Cancer.

Objectives: We aimed to identify the risk factors associated with pelvic lymph node metastasis (LNM) at each anatomic location in patients with stage IB1 cervical cancer. Methods: A primary cohort of 728 patients with stage IB1 cervical cancer who underwent radical hysterectomy and systematic pelvic lymphadenectomy were retrospectively studied. All removed pelvic nodes (N=20,134) were pathologically examined. The risk factors for LNM in different anatomic regions (obturator, internal iliac, external iliac, and common iliac) were evaluated by multivariate logistic regression analyses. Nomograms were generated from the primary cohort and validated in another external cohort (N=242). The performance of the nomogram was assessed by its calibration and discrimination. Overall survival and progression-free survival in patients with different LNM patterns were compared. Results: LNM was found in 266 (1.3%) removed nodes and 106 (14.6%) patients. The incidences of LNM at the obturator, internal iliac, external iliac, common iliac, and parametrial regions were 8.5%, 5.4%, 4.7%, 1.9% and 1.8%, respectively. Among others, tumour size and lymph-vascular space invasion (LVSI), which are preoperatively assessable, were identified as independent risk factors of LNM in the common iliac region and the lower pelvis, respectively, and age was an additional independent risk factor of obturator LNM. The negative predictive values of tumour size <2 cm for common iliac LNM and negative LVSI combined with older age (> 50 years) for obturator LNM were 100% and 98.7%, respectively. A nomogram of these two factors showed good calibration and discrimination (concordance index, 0.761 in the primary cohort and 0.830 in validation cohort). The patients with common iliac LNM had poorer survival than those with LNM confined to the lower pelvis, while the differences in survival between patients with LNM confined to one node, one region or single side and those with more widely spreading LNM were not statistically significant. Conclusions: Tumour size, LVSI and age are region-specific risk factors for pelvic LNM in IB1 cervical cancer, which could be used to allocate the appropriate extent of pelvic lymphadenectomy.

Retrospective analysis of the incidence and predictive factors of parametrial involvement in FIGO IB1 cervical cancer.

BACKGROUND AND OBJECTIVES: Radical surgery is the standard primary treatment for patients with stage IB1 (FIGO 2009 staging) cervical cancer due to latent parametrial involvement. Recent studies suggested that less radical surgery was applicable for patients with no or low risk of parametrial involvement. In this study, we aimed to determine the incidence and possible predictive factors of parametrial involvement in patients with stage IB1 cervical cancer so as to evaluate whether less radical surgery was suitable for selected patients. METHODS: Clinical data of patients who underwent type C radical hysterectomy with pelvic lymphadenectomy and diagnosed as stage IB1 cervical cancer at Union Hospital, Wuhan, China from October 2014 to December 2017 were collected and analysed retrospectively. The incidence of parametrial involvement was calculated and the risk factors for parametrial involvement were evaluated by univariate and multivariate logistic regression. RESULTS: Among 282 eligible patients, 33 (11.7%) had parametrial involvement. Postmenopause, lymphovascular space invasion (LVSI), lymph node metastasis (LNM), deep stromal invasion (outer 1/3) and tumor size larger than 2 cm were statistically associated with parametrial involvement. Multivariate analysis showed that LNM (OR = 11.431; 95%CI: 3.455 - 37.821), deep stromal invasion (OR = 6.080; 95%CI: 1.814 - 20.382) and LVSI (OR = 7.147; 95%CI: 1.863-27.411) remained as independent risk factors for parametrial involvement in patients with stage IB1 cervical cancer. CONCLUSIONS: The incidence of parametrial involvement in stage IB1 cervical cancer is non-negligible. Only LNM, LVSI and deep stromal invasion were independent predictors, which were not easy to evaluate accurately before surgery. Less radical surgery requires modified pre-treatment evaluation methods and prospective data support.

Topographic distribution of lymph node metastasis in patients with stage IB1 cervical cancer: an analysis of 8314 lymph nodes.

BACKGROUND: Systematic pelvic lymphadenectomy or whole pelvic irradiation is recommended for the patients with stage IB1 cervical cancer. However, the precise pattern of lymphatic tumor spread in cervical cancer is unknown. In the present study we evaluated the distribution of nodal metastases in stage IB1 cervical cancer to explore the possibilities for tailoring cancer treatment. METHODS: A total of 289 patients with cervical cancer of stage IB1, according to FIGO 2009, were retrospectively analyzed. All patients underwent laparoscopic radical hysterectomy (Querleu and Morrow type C2) and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy (level 2 or level 3 according to Querleu and Morrow) from October 2014 to December 2017. Lymph nodes removed from 7 well-defined anatomical locations as well as other tissues were examined histopathologically, and typed, graded, and staged according to the WHO/IARC classification. RESULTS: Totally 8314 lymph nodes were analyzed with the average number of 31.88 ± 10.34 (Mean ± SD) lymph nodes per patient. Nodal metastases were present in 44 patients (15.22%). The incidence of lymphatic spread to different anatomic sites ranged from 0% (presacral) to 30.92% (obturator nodes). Tumor size above 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion were shown to be significantly correlated with the higher risk of lymphatic metastasis, while obesity (BMI ≥ 25) was independently negatively associated with lymphatic metastases. CONCLUSIONS: The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. Individual treatment could be considered for the selected low-risk patients who have smaller tumors and obesity and lack of the parametrial invasion or LVSI.

EZH2/H3K27Me3 and phosphorylated EZH2 predict chemotherapy response and prognosis in ovarian cancer.

BACKGROUND: EZH2 acts as an oncogene through canonical pathway EZH2/H3K27Me3 and uncanonical pathway pAkt1/pS21EZH2 in many solid tumors including ovarian cancer. However, the clinical value of EZH2/H3K27Me3 and pAkt1/pS21EZH2 remain unclear. In the current study, we aim to investigate the correlation between these two pathways to clinical-pathological parameters and prognosis. METHODS: EZH2, H3K27Me3, pAkt1 and pS21EZH2 expression were evaluated by tissue micro-array and immunohistochemistry in a cohort of ovarian cancer patients. The results were analyzed based on clinical characteristics and survival outcomes. RESULTS: EZH2, H3K27Me3, pAkt1 and pS21EZH2 were universally expressed in ovarian cancer specimens with a positive expression rate of 81.54% (53/65), 88.89% (48/54), 63.07% (41/65) and 75.38% (49/65). EZH2-pS21EZH2 (Spearman r = 0.580, P < 0.0001) and pS21EZH2-pAkt1 (Spearman r = 0.546, P < 0.0001) were closely correlated while EZH2- H3K27Me3 were less closely correlated (Spearman r = 0.307, P = 0.002). Low pS21EZH2 associated with better chemotherapy response (OR = 0.184; 95% CI [0.052-0.647], P = 0.008) according to logistic regression with an area under the curve of 0.789 (specificity 89.36%, sensitivity 68.42%) by ROC analysis and predicted improved progression-free survival (HR = 0.453; 95% CI [0.229-0.895], P = 0.023) as indicated by multivariate cox regression. A combination of EZH2low/H3K27Me3low status predicted better chemotherapy response (OR = 0.110; 95% CI [0.013-0.906], P = 0.040) and better progression-free survival (HR = 0.388; 95% CI [0.164-0.917], P = 0.031). The results suggested that EZH2/H3K27Me3 and pEZH2 predicted chemotherapy response and progression-free survival in ovarian cancer.

Tumor cell­fibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer.

Ascitic multicellular aggregates (MCAs) promote peritoneal metastasis of ovarian cancer. The aim of the present study was to elucidate the role of cancer­associated fibroblasts (CAFs) in MCA formation and metastasis in patients with high­grade serous ovarian cancer (HGSOC). Immunohistochemistry was used to identify the cell phenotypes and the presence of CAFs in ascitic MCAs. The role of CAFs in tumor­cell MCA formation was assessed by co­culture in suspension. Primary ascitic tumor cells and omental CAFs were used to generate ex vivo MCAs in hanging drops, and the invasiveness of MCAs was evaluated by mesothelial clearance and adhesion assays in vitro and in vivo. MCAs containing CAFs and tumor cells were identified in the ascitic fluid. CAFs facilitated tumor cell aggregation and compaction to form MCAs, and enhanced the mesothelial clearance and adhesion abilities of tumor­cell MCAs. These findings suggest that ascitic CAFs promote peritoneal metastasis by forming heterotypic aggregates with tumor cells, and that they may serve as potential targets for the treatment of HGSOC.

Progress in the Study of Lymph Node Metastasis in Early-stage Cervical Cancer.

Spread into regional lymph node is the major route of metastasis in cervical cancer. Although lymph node status is not involved in the International Federation of Gynecology and Obstetrics staging system of uterine cervical cancer, the presence or absence of lymph node metastasis provides important information for prognosis and treatment. In this review, we have attempted to focus on the incidence and patterns of lymph node metastasis, and the issues surrounding surgical assessment of lymph nodes. In addition, the preoperative prediction of lymph node status, as well as the intraoperative assessment by sentinel nodes will be reviewed. Finally, lymph node micrometastasis also will be discussed.

miR-27a inhibits cervical adenocarcinoma progression by downregulating the TGF-ßRI signaling pathway.

High-risk human papillomavirus infection is essential for the malignant transformation of cervical cancer and can inhibit host miR-27a expression. We investigated the role and mechanism of miR-27a in cervical cancer progression. miR-27a is decreased in cervical cancer cell lines and miR-27a-agomir inhibited the cell proliferation, migration, and invasion properties of HeLa (adenocarcinoma) cells, but not in SiHa cells (squamous cell carcinoma). Luciferase assays revealed that miR-27a directly targets the 3'-UTR of transforming growth factor beta receptor I (TGF-ßRI) and downregulates TGF-ß signaling. The co-transfection of a TGF-ßRI expression vector largely restored the inhibition of TGF-ß signaling, cell proliferation, migration, and invasion mediated by miR-27a-agomir. Also, miR-27a-agomir slows down the growth of subcutaneous HeLa xenografts and downregulates the TGF-ßRI expression and TGF-ß signaling in tumor in vivo. Tissue microarray analysis revealed a low miR-27a level in adenocarcinoma cells, but not in squamous cell carcinoma cells, which was negatively associated with TGF-ßRI expression. High TGF-ßRI correlated with deep stromal invasion and lymph node metastasis. These results suggest that miR-27a acts as a tumor suppressor in cervical cancer, especially in adenocarcinoma, by inhibiting TGF-ßRI signaling pathway. Thus, enhancing miR-27a expression and function may be a novel treatment strategy for cervical adenocarcinoma.

The clinicopathological features and prognosis of tumor MSI in East Asian colorectal cancer patients using NCI panel.

AIM: To compare test results obtained from a PCR assay for the National Cancer Institute (NCI) five loci criteria for detecting microsatellite instability (MSI) with those obtained from immunohistochemistry of mismatch repair and a five-mononucleotide site amplification system in East Asian patients with colorectal cancer. PATIENTS & METHODS:  A total of 245 East Asian patients with colorectal cancer were studied retrospectively at our institution. RESULTS: The consistency of the NCI panel PCR method compared with detection of mismatch repair protein expression by immunohistochemistry was 0.898. High level MSI (MSI-H) status was correlated with the Tumor, Node, Metastasis stage, tumor location site, metastasis, tumor grade, mucinous histological type and BRAF-type mutations. CONCLUSION: The NCI panel PCR assay has excellent sensitivity and specificity for detecting MSI in an East Asian population.

Overexpression of cofilin correlates with poor survival in breast cancer: A tissue microarray analysis.

Cofilin, a key regulator of actin cytoskeleton dynamics, is considered to be involved in cellular migration, tumor invasion and mitosis, and its activity is increased in cancer cells. To address the association between cofilin and breast cancer prognosis, which is unclear at present, cofilin expression was analyzed in tissue microarrays of tumors from 310 patients with breast cancer via immunohistochemistry. In a multivariate Cox regression analysis, a high expression of cofilin in tumor cells correlated significantly with shorter overall survival (hazard ratio, 2.22; 95% confidence interval, 1.35-3.66, P=0.002, and with the Nottingham histologic grade, Ki-67 status and human epidermal growth factor receptor 2 status (P=0.031, 0.001, and 0.001, respectively). Cofilin expression was not observed as correlated with estrogen or progesterone receptor expression, tumor size or lymph node status. These data demonstrate that cofilin is associated with poor outcome, thereby suggesting that it is a potential prognostic factor in breast cancer.

Cervical cancer cell-derived angiopoietins promote tumor progression.

Metastatic or recurrent cervical cancer has limited treatment options and a high rate of mortality. Although anti-vascular endothelial growth factor drugs have shown great promise as a therapeutic target for treatment of advanced cervical cancer, drug resistance and class-specific side effects negate long-term benefits. The identification of alternative anti-angiogenic factors will be critical for future drug development for advanced or recurrent cervical cancer. In this study, we found that angiopoietins and Tie receptors were highly expressed in cervical cancer cells. Tie-2 expression in tumor cells predicted poorer prognosis. Wound closure assay and Transwell assay showed that upregulated or downregulated Ang-1 and Ang-2 expression promoted or reduced cervical cancer cell lines migration and invasion, respectively. In subcutaneous xenograft models of cervical cancer, downregulation of Ang-1 and Ang-2 attenuated tumor growth. The expression of vimentin and endomucin and microvessel density were all significantly decreased in the siAng-1 group and siAng-2 group relative to the infection control group. Our data support that dual inhibition of Ang-1 and Ang-2 may be an alternative target for anti-angiogenic adjuvant therapy in advanced or recurrent cervical squamous cell cancer.

Let-7e sensitizes epithelial ovarian cancer to cisplatin through repressing DNA double strand break repair.

BACKGROUND: Resistance to platinum-based chemotherapy remains a great challenge for ovarian cancer treatment. The human let-7 family contains 13 members located on nine different chromosomes, and most members have been implicated in the modulation of drug sensitivity in cancers. Our previous study showed that deregulation of let-7e in epithelial ovarian cancer (EOC) promoted the development of resistance to cisplatin. In the present study, we aimed to investigate the underlying mechanism and further evaluate the clinical value of let-7e in predicting chemo-response and prognosis in EOC. RESULTS: In situ hybridization assays revealed a significantly decreased expression of let-7e in chemo-resistant EOC tissues compared with chemo-sensitive cases. Transfection with let-7e agomir sensitized EOC cells to cisplatin, down-regulated BRCA1 and Rad51 expression, and repressed the repair of cisplatin-induced DNA double strand break, while let-7e inhibitor exerted the opposite effects. In human EOC tissues, BRCA1 and Rad51 levels were increased in the chemo-resistant group compared with the sensitive group and were negatively correlated with let-7e. Low let-7e and high Rad51 were significantly associated with poor progression-free survival and overall survival and multivariate regression analyses showed that let-7e was an independent predictor for overall survival and chemotherapy response in EOC. Receiver operating characteristic analysis indicated that let-7e level was highly predictive of resistance to platinum-taxane chemotherapy with an area under the curve of 0.826. CONCLUSIONS: In EOC, low let-7e leads to activation of BRCA1 and Rad51 expression and subsequent enhancement of DSB repair, which in turn results in cisplatin-resistance. Let-7e is a potential predictor for survival and chemo-response in EOC and re-expression of let-7e might be an effective strategy for overcoming chemo-resistance.

Dephosphorylated cofilin expression is associated with poor prognosis in cases of human breast cancer: a tissue microarray analysis.

BACKGROUND: Proteins in the cofilin pathway regulate actin dynamics and may be involved in cancer cell migration and invasion. However, there are no direct data that suggest that dephosphorylated cofilin can affect breast cancer prognosis. METHODS: We assessed the expressions of cofilin and phosphorylated cofilin (P-cofilin) in breast cancer tissue microarrays (290 patients, mean follow-up: 95.7±2.49 months) to evaluate dephosphorylated cofilin and its relationship with breast cancer prognosis. The associations of pathological characteristics with cumulative survival were evaluated using Kaplan-Meier analysis. RESULTS: Univariate analyses revealed that overall survival was associated with cofilin levels, N category, TNM stage, estrogen receptor status, progesterone receptor status, and molecular subtypes. Cofilin status and TNM stage independently affected overall survival, although P-cofilin expression was not associated with patient survival. In the P-cofilin-negative subgroup, cofilin expression was significantly associated with patient survival, although cofilin expression was not significantly associated with patient survival in the P-cofilin-positive subgroup. We further analyzed the P-cofilin-negative cases and found that Ki-67 expression was significantly elevated in the subgroup that was strongly positive for cofilin (P=0.002). CONCLUSION: Among P-cofilin-negative patients with breast cancer, cofilin expression defines a population of patients with lower overall survival, which suggests that dephosphorylated cofilin expression might predict the prognosis in cases of P-cofilin-negative breast cancer. Furthermore, our results suggest that inhibitors of dephosphorylated cofilin expression may provide therapeutic benefits in patients with breast cancer.

High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk.

OBJECTIVES: This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. METHODS: The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. RESULTS: Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P < 0.001). Nine predictive models for recurrence were established, in which HTB was combined with recognized risk factors. The model using of at least two risk factors of HTB, tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. CONCLUSIONS: Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification.

Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer.

Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression.

KRAS mutation in adenocarcinoma of the gastrointestinal type arising from a mature cystic teratoma of the ovary.

Mature cystic teratomas (MCT) in the ovary rarely undergo malignant transformation. Moreover, adenocarcinoma of the gastrointestinal type is much rarer. We present two cases of perimenopausal female pateints with mature cystic teratoma of single ovary, while local adenocarcinoma arising in the MCT. The malignancies showed immunohistochemical features of intestinal differentiation, such as strong positivity for CDX-2, villin and CK-20, and negativity for CK-7. Furthermore, the mutation analysis of molecular alteration revealed a KRAS gene mutation in the intestinal adenocarcinoma part, extending into benign intestinal-type epithelium linings. Yet the mutation was not present in the epidermal component of the teratoma. We present these as two unique cases of mucinous adenocarcinoma of the intestinal type arising from mature cystic teratoma. Moreover, we also submit that this KRAS mutation might contribute to identify malignant transformation of a MCT and suggest possible effect on targeted treatment decisions for anti-epidermal growth factor receptor (EGFR) therapy in metastasized patients.