Combined Clear Cell Renal Cell Carcinoma and Chromophobe Renal Cell Carcinoma: A Case Report.

Renal cell carcinoma (RCC) is a diverse array of cancers arising from renal tubular epithelial cells. RCC presenting with distinct morphological subtypes, such as the simultaneous presence of chromophobe RCC (chRCC) and clear cell RCC (ccRCC) lesions within the same kidney, is rare. We present the case of a 79-year-old female with a history of breast cancer who presented to our facility with right flank pain. Further investigations using CT of the abdomen and pelvis revealed a Bosniak type 4 cyst with a mural nodule in the right kidney. Furthermore, another well-defined, solid lesion measuring 2.8 × 2.6 cm was observed in the same area. The patient underwent a right radical nephrectomy. The macroscopic examination of the kidney revealed the presence of three cysts, with the largest measuring up to 7.5 cm. Moreover, a distinctly demarcated, golden-yellow, solid mass was discerned in the superior pole of the kidney. The mass showed a heterogeneous cut surface with solid and cystic components, measuring 2.8 × 2.6 × 2.0 cm. A less extensive but well-defined, uniform tan mass was also identified within the wall of the largest cyst, which measured 1.2 × 1.0 × 0.7 cm. At this point, the diagnosis of ccRCC and chRCC was established.

Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume.

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

[Local resection of small intestine neuroendocrine neoplasms (SI-NEN) : Current principles]. / Lokale Resektion von neuroendokrinen Tumoren des Dünndarms (SI-NEN) : Aktuelle Prinzipien.

BACKGROUND: Neuroendocrine tumors of the small bowel (small intestine neuroendocrine neoplasms, SI-NEN) are the most frequent tumors of the small intestine and approximately 30-40% are still surgically treatable with curative intent at the time of diagnosis. Certain surgical principles must be followed for optimal oncological outcomes and good postoperative quality of life. METHODS: Based on international guidelines and own experiences, the locoregional surgical treatment of SI-NENs is presented. RESULTS: Locoregional SI-NENs should always be resected if technically feasible, as only this approach can achieve a long-term cure and even small primary tumors (< 10 mm) often already show lymphatic metastasis. The resectability of SI-NENs and their difficulty depend on the extent of lymphatic metastasis, which should be assessed based on preoperative imaging of the extent around the superior mesenteric artery. Currently, the surgical gold standard for SI-NENs is open surgery with bidigital palpation of the entire small intestine followed by primary tumor resection via small bowel segment resection, right hemicolectomy or ileocecal resection and vessel-sparing, and therefore organ-preserving lymphadenectomy (≥ 8 lymph nodes). The guidelines consider that laparoscopic or robotic approaches are justified only for early stages of SI-NENs. CONCLUSION: Guideline-compliant surgical treatment of locoregional SI-NEN enables recurrence-free long-term survival with good quality of life.

Predictors and outcomes of recurrent retroperitoneal liposarcoma with multiple tumors.

Background: Retroperitoneal liposarcoma (RLS) is a rare but severe disease. Repeated postoperative recurrence with multiple tumors is a therapeutic dilemma. The clinical outcomes and survival predictors of recurrent RLS with multiple tumors remain to be explored. Methods: Patients with recurrent RLS were retrospectively analyzed. Univariate and multivariate analysis was performed to find independent prognostic factors that were correlated with Overall survival (OS) or progression-free survival (PFS). Factors significant in univariate analysis were further included into multivariate Cox proportional hazards regression model. The nomogram model was built to predict the survival status of patients. Variables that were significant in multivariable analysis were added to the internally validated nomogram models. The analysis of OS and PFS was performed by Kaplan-Meier analysis and log-rank test. Results: A total of 113 recurrent RLS patients with multiple tumors were enrolled in the study. The 1-, 3-, and 5-years OS (PFS) rates were 70.7% (76.1%), 35.9% (76.1%), and 30.9% (76.1%), respectively. Univariate and multivariate analyses showed that number of surgeries, resection methods, tumor size, status of pathological differentiation, pathological subtypes, and recurrence patterns were important prognostic factors for OS or PFS (each p < 0.05). Nomogram models were established to efficiently predict the prognostic status of patients. Patients with the local recurrence (LR) pattern had a poor prognosis and would derive no survival benefit from combined organ resection and R0/R1 resection (each p < 0.05). Conclusion: RLS patients recurrence with multiple tumors had a poor prognosis. Those patients should be followed up more frequently after surgery. The strategies of aggressive resection may not improve the survival of patients with LR pattern in the retroperitoneum. Prognostic factors in the efficient nomogram models should be considered in the individualized clinical management of recurrent RLS with multiple tumors.

Robotic Radiosurgical Boost After Whole-Brain Radiotherapy for 12 Brain Metastases: En Bloc Consecutive Irradiation With Comprehensively Optimized Single Plan for Eight Lesions Totaling 118 cc.

General radiotherapeutic management for >10 brain metastases (BMs) totaling >100 cm3, including multiple large lesions (>10-30 cm3) in close proximity, demonstrated limited efficacy and/or safety. We describe a case of 12 BMs, summating 122.2 cm3, including a 39.6 cm3 maximum lesion and adjacent ones. The patient had an 8.1-year treatment history for recurrent/metastatic breast cancer refractory to endocrine and chemotherapy. BMs were treated with conventional whole-brain radiotherapy (WBRT) with 30 Gy/10 fractions (fr), followed by an immediate stereotactic radiosurgery (SRS) boost with 27 Gy/5 fr (52-64% isodoses) which covers the gross tumor boundaries of selected eight lesions (total 118.4 cm3). The SRS dose was defined to ensure the cumulative biologically effective dose (BED10) of just ≥80 Gy while minimizing the risk of radiation injury. The SRS was performed using a CyberKnife (CK) robotic system (Accuray Incorporated, Sunnyvale, California, United States) with a variable-sized collimator (10-40 mm), for which en bloc consecutive irradiation, using 215 beams based on a comprehensively optimized single plan (path), was adopted. The treatment time per fraction was ≤45 min (mean 5.6 min per lesion). Afterward, BMs demonstrated remarkable regression over six months, causing the total residual visible lesions of 12.6 cm3 (10.3%) at 11.4 months, despite the absence of obvious lesion shrinkage during the radiotherapy. WBRT, followed by an immediate 5-fr SRS boost with a total BED10 of 80 Gy to large and/or culprit lesions, can be an efficacious and safe treatment option for multiple BMs, totaling >120 cm3. En bloc consecutive irradiation with a single path provides overwhelmingly more efficient delivery for treating multiple lesions using CK in terms of irradiation time and comprehensive reduction of normal brain dose compared to individual planning. Volumetric-modulated arc-based >10-fr SRS with simultaneously integrated reduced-dose WBRT may be an alternative to further enhance efficacy and safety.

Prevalence and spectrum of pathogenic variants among patients with multiple primary cancers evaluated by clinical characteristics.

BACKGROUND: Multiple primary cancers (MPCs) are a hallmark of cancer predisposition syndromes. Here the frequency of germline pathogenic variants (PVs) among patients with MPCs is reported. METHODS: Patients with MPCs who underwent multigene panel testing from March 2012 to December 2016 were studied. Eligible patients had an analysis of 21 genes: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53. The frequencies of PVs by sex, number of cancers, and age at diagnosis were compared with 2-sided χ2 tests or Fisher exact tests when the number was <10. RESULTS: Among the 9714 patients analyzed, most were female (91.1%) and White (71.0%); the median age at testing was 63 years, and the median ages at first and second cancer diagnoses were 49 and 58 years, respectively. Overall, 1320 (13.6%) had PVs. The prevalence of PVs increased with the number of primary cancers (PCs): 13.1% with 2 PCs, 15.9% with 3 PCs, and 18.0% with ≥4 PCs (P = .00056). Differences in the prevalence of PVs by age at diagnosis were significant: 14.7% with 2 PCs at an age < 50 years, 15.8% with 1 PC at an age < 50 years, and 12.0% with all PCs at an age ≥ 50 years (P = 2.07E-05). PVs by the age at second cancer diagnosis were also significant: 14.7% at an age < 50 years, 13.9% at an age of 50 to 69 years, and 11.4% at an age ≥ 70 years (P for trend = .005). CONCLUSIONS: Among patients with MPCs, there is a high frequency of germline PVs, with a higher frequency found among patients with a higher number of PCs. These findings suggest that genetic testing should be considered even among patients who are older at the diagnosis of an additional primary malignancy.

Combined response of advanced cutaneous squamous cell carcinoma and renal cell carcinoma to immunotherapy: a case report.

Immune checkpoint inhibitors have significantly improved the therapeutic scenario of many different advanced malignancies and could be an effective treatment strategy in synchronous or metachronous tumors. The authors describe the clinical case of a patient who experienced a long-lasting response of his metastatic renal cell carcinoma and an optimal response of his locally advanced cutaneous squamous cell carcinoma to immunotherapy. The systemic treatment was chosen based on a literature review of several clinical reports, since there was no prospective study on anti-PD-1 blockade activity in cutaneous squamous cell carcinoma when the patient started the treatment. This clinical case supports the growing evidence for immunotherapy as a valid treatment option across different types of advanced tumors.

Immunotherapy is an effective treatment strategy across different cancer types and could be a valid treatment strategy in patients with multiple malignant tumors. In this scenario, in fact, the main challenge is to choose a systemic treatment which could be active on both tumors with an acceptable toxicity profile. The authors report the clinical case of a patient with metastatic renal cell carcinoma and a disfiguring cutaneous cancer of the zygomatic region who experienced a durable response of the renal tumor and almost a complete clinical response of the cutaneous cancer.

Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: A propensity score matching analysis.

BACKGROUND: Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors (GIST). The diagnosis, treatment and follow-up strategies of MGISTs is not specifically described in guidelines. AIM: To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs (SGISTs). METHODS: Patients diagnosed with primary GISTs from March 2010 to January 2020 were included. Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes, propensity score matching was performed according to comorbidities, body mass index, tumor location, mitotic index, sex, age and American Society of Anesthesiologists score. Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared. RESULTS: Among the entire cohort of 983 patients, the incidence of MGISTs was 4.17%. Before matching, patients with MGISTs and those with SGISTs had disparities in body mass index, surgical approach, tumor size and mitotic index. After 1:4 ratio matching, the clinical baseline data were comparable. The 5-year progression-free survival rate was 52.17% in the MGIST group and 75.00% in the SGIST group (P = 0.031). On multivariate analysis, tumor location, tumor size, mitotic index, imatinib treatment and MGISTs (hazard ratio = 2.431, 95% confidence interval = 1.097-5.386, P = 0.029) were identified as independent prognostic factors of progression-free survival. However, overall survival was similar between the SGIST and MGIST groups. CONCLUSION: Patients with MGISTs had poorer progression-free survival than patients with SGISTs. Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.

Cutaneous mast cell tumor in a captive Bush dog (Speothos venaticus): pathological and immunophenotypical aspects - case report / Mastocitoma cutâneo em um cachorro-do-mato vinagre (Speothos venaticus) de cativeiro: aspectos patológicos e imunofenotípicos - relato de caso

A senile male captive bush dog (Speothos venaticus) presented a small perianal cutaneous nodule. Histologically, there was an ulcerated round cell tumor composed of well differentiated mast cells with abundant intracytoplasmic purple Giemsa-positive granules, with a diffuse eosinophilic infiltrate. Immunohistochemistry revealed that 30% of the neoplastic cells were positive for Kit in the cytoplasm and cell membrane, and all neoplastic cells were negative for MAC and CD3. Less than 10% of the neoplastic cells were positive for Ki67. At necropsy other primary tumors were identified in this animal, including an intestinal adenoma, an adrenal cortex adenoma and a testicular interstitial cell tumor.(AU)

Um cachorro-vinagre (Speothos venaticus) apresentou um nódulo cutâneo pequeno na região perianal. Histologicamente havia neoplasia cutânea de células redondas e ulcerada, constituída por mastócitos bem diferenciados, com abundantes grânulos citoplasmáticos metacromáticos na coloração de Giemsa e infiltrado eosinofílico difuso. A imuno-histoquímica demonstrou que 30% das células neoplásicas eram positivas para a proteína Kit no citoplasma e na membrana celular. As células foram negativas para MAC e CD3. Menos de 10% das células neoplásicas foram positivas para Ki67. Durante a necropsia, foram identificados outros tumores primários, como adenoma intestinal, adenoma cortical da adrenal e tumor de células intersticiais do testículo.(AU)

Multiple jejunal gastrointestinal stromal tumors and Neurofibromatosis type 1: A rare association.

INTRODUCTION AND IMPORTANCE: The association between gastrointestinal stromal tumor (GIST), mesenchymal tumor arising from the interstitial cells of cajal and Neurofibromatosis type 1 (NF1), an autosomal dominant disease has been reported in the literature. GIST in NF1 patients are multiple and located in the small intestine. Tumorigenesis in NF1 associated GIST is different to that of sporadic GIST and hence the treatment. Here we report a rare case of an NF1 patient with multiple jejunal GISTs. CASE PRESENTATION: We here present a rare case of a 57-year-old male diagnosed with NF1 30 years back, presented in our emergency department with complaints of black, tarry stools later diagnosed to have multiple GIST in jejunum. Contrast enhanced computed tomography (CECT) of the abdomen showed a large 10.1 × 7.33 × 6.2 cm heterogeneous, exophytic, solid mass with cystic areas originating from the jejunum. The microscopic examination of the specimen showed spindle shaped tumor cells while immunohistochemistry showed CD117 (c-KIT) and DOG-1 positivity. The primary treatment was complete surgical excision of the tumor. CLINICAL DISCUSSION: The incidence of GISTs in NF1 patient is around 6-7%; however, concomitant presence of multiple GISTs is rare. CECT of abdomen along with histopathological and immunohistochemistry studies are diagnostic. The management of GIST includes surgical and adjuvant therapy methods based on the tumorigenesis and recurrent risk stratification. CONCLUSION: Early clinical suspicion and imaging aids in early detection of the tumor in patients with NF1 presenting with gastrointestinal symptoms. Postoperatively, screening for recurrence with radiology is of utmost importance.

[Synchronous schwannoma and ependymoma of the cauda equina]. / Sochetanie shvannomy i ependimomy konskogo khvosta spinnogo mozga.

The article presents a case of surgical treatment of primary multiple benign tumors of the cauda equine of different histological origin: spinal nerve root schwannoma and ependymoma of the filum terminale.

[Combination of tumors of different histogenesis in pediatric neurosurgery]. / Sochetanie opukholei razlichnogo gistogeneza v detskoi neirokhirurgii.

Multiple gliomas are determined by synchronous two or more tumors located in different brain regions. It is important to distinguish multiple primary tumors and metastatic brain lesion. In the first case, tumor spread can`t be explained by dissemination along the cerebrospinal fluid pathways, commissural fibers or local metastases. Multiple primary tumors with different histological structures are called bidermal neoplasms. Surgery is preferred in these patients with severe symptoms. The purpose of surgery is maximum resection of tumor. Follow-up may be advisable for small tumors without clinical manifestations. Treatment of multiple gliomas includes surgery, radiotherapy and chemotherapy. Multiple tumor process in children is much more severe compared to a single neoplasia that requires neurological and neuroimaging control and determines treatment strategy. The authors report 3 children with multicentric gliomas, discuss the various aspects of diagnosis and treatment of multiple gliomas and formulate the recommendations for the treatment based on own clinical experience and literature data.

[Multiple primary tumor of hematopoietic tissue: myeloid sarcoma in combination with mantle cell lymphoma. Case report].

The prevalence of multiple primary tumors has significantly increased last time. The question of choosing the optimal tactics of therapy today not fully resolved. Particular interest is the simultaneous detection of two neoplasms of similar origin in one study biopsy material. This publication presents a case of simultaneous diagnosis of myeloid sarcoma and mantle cell lymphoma in a 65-year-old patient, which required use of two different chemotherapy protocols. This example shows the need to use an extended diagnostic approach at all stages of the therapy, which allows choosing right tactics of therapy and achieving complete remission of two neoplasms.

Hepatoblastoma with multiple tumors in a school-aged child.

Clinicians need to consider hepatoblastoma in the differential even in school-aged children or adolescents presenting with multiple liver tumors.

Synchronous sporadic bilateral multiple chromophobe renal cell carcinoma accompanied by a clear cell carcinoma and a cyst: A case report.

BACKGROUND: Renal cell carcinomas are usually unilateral. However, they are bilateral in 2% to 4% of sporadic cases and is considerably more common in familial cases. Synchronous sporadic bilateral multiple chromophobe renal cell carcinoma (CHRCC) with different subtypes is rare. CASE SUMMARY: In this case report, we describe a case of synchronous bilateral CHRCC with two histological variants, accompanied by a clear cell carcinoma and a cyst in a 50-year-old male. The patient underwent retroperitoneal laparoscopic bilateral nephron-sparing surgery and there was no serious postoperative renal dysfunction. CONCLUSION: We report a rare case of synchronous bilateral CHRCC with two histological variants associated with a clear cell carcinoma and a cyst.

Synchronous detection of SDHA-related gallbladder paraganglioma and pancreatic neuroendocrine tumor.

Primary gallbladder paragangliomas (PGLs) are exceedingly rare. PGLs are extraadrenal neuroendocrine tumors that are morphologically inseparable from intraadrenal pheochromocytomas. PGLs and pheochromocytomas are some of the most heritable tumor types in the body and are often associated with other tumors or part of a genetic syndrome. We report a case of gallbladder PGL presenting synchronously with pancreatic neuroendocrine tumor (NET) and pulmonary IgG4-related disease in a 74-year old male patient with disseminated prostate adenocarcinoma. Due to the high rate of germline mutations and the possible syndromal manifestation of PGLs as well as pancreatic NETs, this patient was offered genetic testing, and a pathogenic SDHA germline mutation was found. Immunohistochemically, there was loss of SDHA and SDHB in the PGL but neither in the NET nor in the prostate adenocarcinoma. To our knowledge, this case is the first report of gallbladder PGL associated with pancreatic NET. It is likely that the identified SDHA germline mutation played a role in the development of gallbladder PGL in this patient.

DLEU1: A Functional Long Noncoding RNA in Tumorigenesis.

BACKGROUND: LncRNA DLEU1 participates in various biological processes, playing an indispensable role in the pathophysiology of human diseases, especially in tumorigenesis and other processes. Besides, it may represent a promising target for biotherapy in numerous tumors. The aim of this review was to reveal the pathophysiological functions and mechanisms of lncRNA DLEU1 in different types of cancer. METHODS: In this review, current studies concerning the biological functions and mechanisms of DLEU1 in tumor development are summarized and analyzed; the related researches are collected through a systematic retrieval of PubMed. RESULTS: DLEU1 is a novel cancer-associated lncRNA that has been proved to be abnormally elevated in various malignancies, containing osteosarcoma, glioma, glioblastoma multiforme, hepatocellular carcinoma, bladder cancer, cervical cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, colorectal cancer, oral squamous cell carcinoma, endometrial cancer, gastric cancer, Burkitt lymphoma and ovarian carcinoma. Besides, lncRNA LDEU1 has been demonstrated involving in the procession of proliferation, migration, invasion and inhibition of apoptosis of cancer cells. CONCLUSION: Long non-coding RNA DLEU1 is likely to represent an available biomarker or a potential therapeutic target in multiple tumors.

Histopathological and molecular study for synchronous lung adenocarcinoma staging.

The presence of multiple synchronous lung cancer with the same histopathological type for a patient is a common situation and an issue for staging. Pathological criteria exist to distinguish multiple primaries from intra-pulmonary metastases of the same tumor, but they lack standardization. We wondered how molecular analysis with a limited Next Generation Sequencing panel could bring further information for tumor staging in this setting. We analyzed 24 patients with a total of 50 tumor nodules (22 pairs, two triplets). We compared histopathological examination with molecular analysis. A total of 50 tumors were molecularly tested. Nucleoli size was associated with molecular analysis concordance (p = 0.047). The presence of lepidic component in any of the two larger tumors was associated with molecular analysis concordance (p = 0.012). For molecular analysis, the proportion of progression-free patients was at the limits of significance (p = 0.054) whereas the presence of lepidic component, architectural concordance, and the concordance of comprehensive histologic assessments was not related to progression-free survival. For two patients with a discordant TTF-1 immunohistochemistry, molecular analysis showed a different mutation. Our results show that a limited NGS panel brings supplementary data to classify synchronous lung adenocarcinoma in most patients. We show that molecular staging seems in accordance with progression-free survival. Histopathological examination alone might not be accurate enough to assess a correct staging for synchronous tumors. We also suggest that TTF-1 immunohistochemistry, for the rare discrepant cases, might be a surrogate to molecular analysis.

Mutation Spectrum of Cancer-Associated Genes in Patients With Early Onset of Colorectal Cancer.

Background: Colorectal cancer (CRC) incidence is rising worldwide, as well as in the Republic of Kazakhstan, while its occurrence is also increasing in the younger population. Hereditary forms associated with the development of colon and rectal cancer and early-onset CRC have never been studied in the population of Kazakhstan. The aim of this research was to investigate the spectrum of CRC-related gene mutations to determine which mutations cause early onset of CRC in the Kazakhstan population. Methods: The study included 125 unrelated patients from Kazakhstan (range 17-50 years in age) with early onset CRC. Genomic DNA was obtained from peripheral blood of the patients. Next-generation sequencing was performed using the TruSightCancer Kit on the MiSeq platform. The Studio Variant was used to annotate and interpret genetic variants. Results: Bioinformatics analysis of Next-generation sequencing data revealed 11,152 variants from 85 genes, of them, 3,790 missense, 6,254 synonymous variants, 44 3'UTR variants, 10 frameshift variants, five stop-gain variants, four in-frame deletions, two splice donors, one splice acceptor variant, and 1,042 intron or non-coding variants. APC, BRCA2/1, ALK, BRIP1, EGFR, FANCA, FANCD2, FANCI, HNF1A, MEN1, NSD1, PMS2, RECQL4, RET, SLX4, WRN, and XPC genes mutated most often. According to the ACMG guidelines and LOVD/ClinVar databases, 24 variants were pathogenic (10 frameshifts, five missenses, five stop-gain, one in-frame deletion, and three splice-site mutations), and 289 were VUS with population frequency <1%, 131 of them were attributed as deleterious. In the study, 50% of all pathogenic mutations found in Kazakhstani patients with early CRC onset were identified in the subgroups with a family history of CRC and primary multiple tumors. In APC, pathogenic mutations were most often (21%). Conclusion: Pathogenic and likely pathogenic mutations were found in 20 (16%) out of 125 patients. Eight novel pathogenic mutations detected in FANCI, APC, BMPR1, ATM, and DICER1 genes have not been reported in previous literature. Given the high frequency and wide spectrum of mutations, NGS analysis must be carried out in families with a history of CRC/CRC-related cancers with the purpose to identify cause-effective mutations, clarify the clinical diagnosis, and prevent the development of the disease in other family members.