Molecular genetics and immunohistochemistry characterization of uncommon and recently described renal cell carcinomas

Renal cell carcinoma （RCC） compromises multiple types and has been emerging dramatically over the recent several decades. Advances and consensus have been achieved targeting common RCCs, such as clear cell carcinoma, papillary RCC and chromophobe RCC. Nevertheless, little is known on the characteristics of several newly-identified RCCs, including clear cell （tubulo） papillary RCC, Xpl 1 translocation RCC, t（6;11） RCC, succinate dehydrogenase （SDH）-deficient RCC, acquired cystic disease- associated RCC, hereditary leiomyomatosis RCC syndrome-associated RCC, ALK translocation RCC, thyroid-like follicular RCC, tubulocystic RCC and hybrid oncocytic/chromophobe tumors （HOCT）. In current review, we will collect available literature of these newly-described RCCs, analyze their clinical pathologic characteristics, discuss their morphologic and immunohistologic features, and finally summarize their molecular and genetic evidences. We expect this review would be beneficial for the understanding of RCCs, and eventually promote clinical management strategies.

Angiogenesis of hepatocellular carcinoma: An immunohistochemistry study

BACKGROUND Although hepatocellular carcinoma(HCC) is one of the most vascular solid tumors, antiangiogenic therapy has not induced the expected results.AIM To uncover immunohistochemical(IHC) aspects of angiogenesis in HCC.METHODS A retrospective cohort study was performed and 50 cases of HCC were randomly selected. The angiogenesis particularities were evaluated based on the IHC markers Cyclooxygenase-2(COX-2), vascular endothelial growth factor(VEGF) A and the endothelial area(EA) was counted using the antibodies CD31 and CD105.RESULTS The angiogenic phenotype evaluated with VEGF-A was more expressed in small tumors without vascular invasion(pT1), whereas COX-2 was rather expressed in dedifferentiated tumors developed in non-cirrhotic liver. The CD31-related EA value decreased in parallel with increasing COX-2 intensity but was higher in HCC cases developed in patients with cirrhosis. The CD105-related EA was higher in tumors developed in patients without associated hepatitis.CONCLUSION In patients with HCC developed in cirrhosis, the newly formed vessels are rather immature and their genesis is mediated via VEGF. In patients with non-cirrhotic liver, COX-2 intensity and number of mature neoformed vessels increases in parallel with HCC dedifferentiation.

The Comparative Study on Ultrastructure and Immunohistochemistry in AFP Negative and Positive Hepatocellular Carcinoma

Summary: To comparatively investigate ultrastructural characteristics and expressions of AFP (alpha-fetoprotein) and Tn (Thomsen-Friedenreich-related antigen) protein in AFP negative (AFP-) and AFP positive (AFP+) primary hepatocellular carcinoma. Fourty-three cases of AFP-and AFP+ hepatocellular carcinoma (HCC) tissues and five cases of normal liver tissues were divided into three groups: control group (normal liver tissue, n=5); AFP+ HCC group (the serum AFP level was higher than 10 ng/ml, n = 22); AFP-HCC group (the serum AFP level was lower than 10 ng/ml, n=21). The ultrastructural morphology was studied by transmission electron microscopy, the expressions of AFP and Tn protein were detected by immunohistochemistry and cell image analysis. 1. The immunohistochemical study showed that (1) the expression intensity and positive rate of Tn protein in AFP-HCC group were markedly higher than that in AFP+ HCC group (P<~0.01); (2) The expression intensity of AFP in AFP-HCC group was lower than that in AFP+ HCC group (P<0.01). 2. The transmission electron microscopy demonstrated that some AFP-HCC cells linked closely with each other, others dispersed loosely just as cultured cells, the remarkable morphologic features in AFP-HCC cells were simple organelles, but they were abundant in the free polyribosomes. In AFP+ HCC group, all the HCC cells linked closely together and were rich organelles in their cytoplasm, especially the rough endoplasmic reticula. In addition, mitochondria and Golgi complex were obviously observed. (1) The AFP and Tn protein had discrepancy distribution in AFP-and AFP+ HCC tissues, Tn protein may be one of the early diagnostic indicators in AFP-HCC; (2) The synthetic locations of the AFP and Tn protein were different in hepatocarcinoma cells by ultrastructural observation.

Signif icance of Sentinel Lymph Node Biopsy and Immunohistochemistry in Diagnosis and Staging of Stage-cN0 Oral Squamous Cell Carcinoma

OBJECTIVE To assess the significance of sentinel lymph node biopsy （SLNB）, serial section and cytokeratin immunohistochemical staining in the diagnosis and staging of Stage-cNO oral squamous cell carcinoma （OSCC）, METHODS A blue stain, 99mTc-dextran SPECT lymphoscintigrapgy and intraoperative y-ray probes were used to examine the sentinel nodes in 31 cases with Stage-oNO oral cancer, The H＆E staining and a cytokeratin AE1/ AE3 immunohistochemistry （IHC） assessment, with serial sections, were conducted to provide results obtained from a routine pathological examination of lymph nodes, The value of the routine pathological examination of the sentinel lymph node （SLN）, serial sections and IHC determination for cervical lymph node metastasis of Stage-cN0 OSCC was appraised, RESULTS A total of 45, 55 and 51 SLNs were examined in 25 （80%）, 31 （100%） and 30 （96,5%） of the cases, by using the blue stain, y-ray probes, and SPECT lymphoscintigraphy, respectively, The average SLNs found in each case of the groups was 1,4 （1 to 3） and there were 1,302 non-NSLNs, Six positive SLN metastases were detected by routine pathological examination, among which 1 case was found to be an accompanied positive metastasis of non-SLN, One positive SLN metastasis was found after examination of serial sections plus routine H＆E staining and 2 were detected using serial sections plus AE3 immunohistochemical staining methods, No positive NSLNs were found in the study, CONCLUSION In order to make more progress in accurate SLNB diagnosis, serial sections and IHC （AE1/AE3） methods can be used for examination of the micrometastases which are difficult to identify by routine pathological sections and H＆E staining.

THE APPLICATION OF IMMUNOHISTOCHEMISTRY IN THE DIFFERENTIAL DIAGNOSIS OF EXTRANODAL LYMPHOMA AND ANAPLASTIC CARCINOMA

Thirty-six cases originally diagnosed histologically as malignant lymphoma (ML) or anaplastic carcinoma were reexamined immunohistochemically by leukocyte common antigen (LCA) and epithelial membrane antigen (EMA). 5/18 cases originally diagnosed as ' anaplastic carcinoma'' and 'anaplastic carcinoma? (ML to be excluded)' , showed positive staining for LCA and negative for EMA; whereas 3 cases originally diagnosed as malignancy unclassified turned out to be ML, with the relevant assay performed.

Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

Primary parenchymal squamous cell carcinoma of the kidney:A case report

BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases reported.CASE SUMMARY This study reports a 51-year-old man with primary SCC of the renal parenchyma.The patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross hematuria.SCC antigen(SCCA)levels were elevated,and imaging revealed a renal mass with associated calculi.The patient underwent laparoscopic unilateral nephrectomy and lymph node dissection.Postoperative pathology confirmed highly differentiated SCC with necrosis in the right renal parenchyma,with negative renal pelvis and ureter.The pathological stage was Pt3aN1M0.Four months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena cava.The patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease progression.CONCLUSION We report a case of primary SCC of the renal parenchyma,a rare renal malignancy.The clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis challenging.According to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum SCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.

Radiomics and molecular analysis:Bridging the gap for predicting hepatocellular carcinoma prognosis

This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the survival of patients with hepatocellular carcinoma(HCC).By integrating radiomics with molecular analysis,the study presented a strategy for accurately predicting the expression of EZH2 from CT scans.The findings demonstrated a strong link between the radiomics model,EZH2 expression,and patient prognosis.This noninvasive approach provides valuable insights into the therapeutic management of HCC.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

Combined hepatocellular cholangiocarcinoma: A clinicopathological update

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

Vaginal clear cell adenocarcinoma in Herlyn-Werner-Wunderlich syndrome:A case report

BACKGROUND Herlyn-Werner-Wunderlich(HWW)syndrome is a rare Müllerian duct anomaly,characterized by a combination of urogenital abnormalities.The occurrence of primary cervico-vaginal carcinomas in patients with HWW syndrome is excep-tionally rare,posing significant challenges for screening,early diagnosis,and effective management.CASE SUMMARY We report a rare case of primary clear cell carcinoma of the vagina complicated in a 40-year-old woman with HWW syndrome.The patient presented with irregular vaginal bleeding for 4 years.On gynecological examination,an oblique vaginal septum was suspected.Surgical resection of the vaginal septum revealed a com-municating fistula and a tumor on the left vagina and the left side of the septum,which was confirmed as clear cell carcinoma.One month later,she underwent a radical hysterectomy,vaginectomy,bilateral salpingo-oophorectomy,and pelvic lymph node dissection.Due to significant side effects,she completed only one course of chemotherapy.A year later,lung metastasis was detected and continued to grow.A thoracoscopic wedge resection of the right upper lobe was performed 4 years after the initial surgery.We also conducted a systemic review of the lite-rature on primary cervical or vaginal carcinoma in HWW syndrome to explore this rare entity.CONCLUSION Cervico-vaginal adenocarcinomas in patients with HWW syndrome are occult,and require early surgical intervention and regular imaging surveillance.

Clinicopathological features and surgical outcomes of four rare subtypes of primary liver carcinoma

Objective：This study aimed to analyze clinicopathological and prognostic features of four rare pathological subtypes of primary liver malignancies to make better understanding of their clinical features.Methods：The clinicopathological data of 114 patients who were diagnosed with histologically proven four subtypes：clear cell carcinoma（CCC）,giant cell carcinoma（GCC）,sarcomatoid carcinoma（SC）,and combined hepatocellular-cholangiocarcinoma（CHC）between October 1998 and August 2015 were reviewed.Their survival data were compared with those of 908 patients with histologically proven common hepatocellular carcinoma（HCC）（early-and advanced-stage HCC）during the same period.Results：The outcome of the CCC group was better than that of the other three subgroups,and was similar to that of the early-stage HCC group.Also,the smallest tumor size and the highest incidence of pseudocapsule formation were observed in the CCC group.The SC group had the worst outcome among these four subgroups;the prognosis was much poorer than that of any other subgroups,even poorer than that of the advanced-stage common HCC group.No statistical difference was observed between the GCC,CHC and advanced-stage HCC groups on survival analysis.The incidences of tumor vascular emboli,TNM staging and non-radical resection were three risk factors of the prognosis.Conclusions：CCC is a low-degree malignancy and relatively favorably prognostic subtype of HCC.However,GCC,SC,and CHC are three rare high-degree malignancy subtypes of HCC with poor prognosis.

New trends in diagnosis and management of gallbladder carcinoma

Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm)gallstones in up to 90%of cases.The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes,GB wall calcification(porcelain)or mainly mucosal microcalcifications,and GB polyps≥1 cm in size.Diagnosis is made by ultrasound,computed tomography(CT),and,more precisely,magnetic resonance imaging(MRI).Preoperative staging is of great importance in decisionmaking regarding therapeutic management.Preoperative staging is based on MRI findings,the leading technique for liver metastasis imaging,enhanced three-phase CT angiography,or magnetic resonance angiography for major vessel assessment.It is also necessary to use positron emission tomography(PET)-CT or ^(18)F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake.Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6%of cases.Multimodality treatment is needed,including surgical resection,targeted therapy by biological agents according to molecular testing gene mapping,chemotherapy,radiation therapy,and immunotherapy.It is of great importance to understand the updated guidelines and current treatment options.The extent of surgical intervention depends on the disease stage,ranging from simple cholecystectomy(T1a)to extended resections and including extended cholecystectomy(T1b),with wide lymph node resection in every case or IV-V segmentectomy(T2),hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y,and adjacent organ resection if necessary(T3).Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery,but much attention must be paid to avoiding injuries.In addition to surgery,novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy(neoadjuvant-adjuvant capecitabine,cisplatin,gemcitabine)have yielded promising results even in inoperable cases calling for palliation(T4).Thus,individualized treatment must be applied.

Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

Clinicopathological features and surgical outcome of patients with fibrolamellar hepatocellular carcinoma(experience with 22 patients over a 15-year period)

AIM To evaluate the clinicopathological features and the surgical outcomes of patients with fibrolamellar hepato-cellular carcinoma(FL-HCC)over a 15-year period. METHODS This is a retrospective study including 22 patients with a pathologic diagnosis of FL-HCC who underwent hepatectomy over a 15-year period. Tumor characteristics,survival and recurrence were evaluated. RESULTS There were 11 male and 11 female with a median age of 29 years(range from 21 to 58 years). Two(9%)patients had hepatitis C viral infection and only 2(9%)patients had alpha-fetoprotein level > 200 ng/m L. The median size of the tumors was 12 cm(range from 5-20 cm). Vascular invasion was detected in 5(23%)patients. Four(18%)patients had lymph node metastases. The median follow up period was 42 mo and the 5-year survival was 65%. Five(23%)patients had a recurrent disease,4 of them had a second surgery with 36 mo median time interval. Vascular invasion is the only significant negative prognostic factor CONCLUSION FL-HCC has a favorable prognosis than common HCC and should be suspected in young patients with non cirrhotic liver. Aggressive surgical resection should be done for all patients. Repeated hepatectomy should be considered for these patients as it has a relatively indolent course.

Eccrine porocarcinoma in the tempus of an elderly woman:A case report

BACKGROUND Eccrine porocarcinoma(EPC)is a rare skin tumor that mainly affects the elderly population.Tumors often present with slow growth and a good prognosis.EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry.However,surgical management alone may be inadequate if the tumor has metastasized.However,currently,surgical resection is the most commonly used treatment modality.CASE SUMMARY A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area,with no obvious itching or pain,for more than four months.Histopathological examination showed small columnar and short spindle-shaped cells;thus,basal cell carcinoma was suspected.However,immunohistochemical analysis revealed the expression of cytokeratin 5/6,p63 protein,p16 protein,and Ki-67 antigen(40%),and EPC was taken into consideration.The skin biopsy was repeated,and hematoxylin and eosin staining revealed ductal differentiation in some cells.Finally,the patient was diagnosed with EPC,and Mohs micrographic surgery was performed.We adapted follow-up visits in a year and not found any recurrence of nodules.CONCLUSION This case report emphasizes the diagnosis and differentiation of EPC.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

Downstaging strategies for unresectable hepatocellular carcinoma

A significant number of patients with hepatocellular carcinoma(HCC)are usually diagnosed in advanced stages,that leads to inability to achieve cure.Palliative options are focusing on downstaging a locally advanced disease.It is wellsupported in the literature that patients with HCC who undergo successful conversion therapy followed by curative-intent surgery may achieve a significant survival benefit compared to those who receive chemotherapy alone or those who are successfully downstaged with conversion therapy but not treated with surgery.Hepatic artery infusion chemotherapy can be a potential downstaging strategy,since recent studies have demonstrated excellent outcomes in patients with colorectal liver metastatic disease as well as primary liver malignancies.

Bilateral squamous cell carcinoma of the temporal bone:A report of two cases and a systematic review of the literature

Objective:two new cases of temporal bone squamous cell carcinoma(TBSCC)with a bilateral occurrence are presented.Furthermore,a review of the literature was performed and the yearly incidence was calculated.Methods:A systematic review of the literature was conducted using PRISMA guidelines.Results:Twenty-two more cases were found in literature.With a total of 24 cases,the calculated yearly incidence of bilateral TBSCC is 49:10^12 A history of chronic otitis or regional radiotherapy was found in respectively 50%and 12%of patients.In nine patients,the tumors developed synchronously(within 6 months)and in 13 metachronously.Conclusions:The calculated incidence is 89 times higher than mathematically expected considering the incidence of unilateral cases.An explanation might be a history of chronic otitis or prior radiotherapy.The tumor staging of both the first tumor group and the contralateral tumor group are similar to unilateral temporal bone squamous cell carcinoma series.

Conversion therapy for unresectable hepatocellular carcinoma:Advances and challenges

Recently,the World Journal of Gastrointestinal Oncology published an article entitled“Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of the literature”,in which the authors shared their successful experience with complete surgical resection after multidisciplinary conversion therapy.The study by Chu et al demonstrates the great challenges that the advanced hepatocellular carcinoma(HCC)poses to surgical oncology,reveals the complexity of conversion therapy for unresectable HCC,emphasizes the important role of a multidisciplinary management model in conversion therapy,and enriches our understanding of the dynamics of personalized treatment for different patients.At present,conversion therapy is a hot research topic in the treatment of unresectable HCC,which has brought new hope to many patients with moderately advanced HCC.However,there are still many urgent problems to be solved in conversion therapy.Here,we would like to further discuss the advances and challenges of conversion therapy for unresectable HCC with the authors and the general readers.