Blastomas of the digestive system in adults:A review

Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast cells.This review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and pancreatoblastoma.Gastroblastoma is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to date.In addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been described.Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty.Pancreatoblastoma,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially neuroendocrine.Diagnostic approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular profiling.The treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some cases.Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of metastases.This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

Update on hepatocellular carcinoma: Pathologists' review

Histopathologic diversity and several distinct histologic subtypes of hepatocellular carcinoma(HCC) are well-recognized. Recent advances in molecular pathology and growing knowledge about the biology associated with distinct histologic features and immuno-profile in HCC allowed pathologists to update classifications. Improving sub-classification will allow for more clinically relevant diagnoses and may allow for stratification into biologically meaningful subgroups. Therefore, immuno-histochemical and molecular testing are not only diagnostically useful, but also are being incorporated as crucial components in predicting prognosis of the patients with HCC. Possibilities of targeted therapy are being explored in HCC, and it will be important for pathologists to provide any data that may be valuable from a theranostic perspective. Herein, we review and provide updates regarding the pathologic sub-classification of HCC.Pathologic diagnostic approach and the role of biomarkers as prognosticators are reviewed. Further, the histopathology of four particular subtypes of HCC:Steatohepatitic, clear cell, fibrolamellar and scirrhous-and their clinical relevance, and the recent consensus on combined HCC-cholangiocarcinoma is summarized. Finally, emerging novel biomarkers and new approaches to HCC stratification are reviewed.

Plexiform fibromyxoma:Review of rare mesenchymal gastric neoplasm and its differential diagnosis

Plexiform fibromyxoma(PF)is a very rare mesenchymal neoplasm of the stomach that was first described in 2007 and was officially recognized as a subtype of gastric mesenchymal neoplasm by World Health Organization(WHO)in 2010.Histologically,PF is characterized by a plexiform growth of bland spindle to ovoid cells embedded in a myxoid stroma that is rich in small vessels.The lesion is usually paucicellular.While mucosal and vascular invasion have been documented,no metastasis or malignant transformation has been reported.Its pathogenesis is largely unknown and defining molecular alterations are not currently available.There are other mesenchymal tumors arising in the gastrointestinal tract that need to be differentiated from PF given their differing biologic behaviors and malignant potential.Histologic mimics with spindle cells include gastrointestinal stromal tumor,smooth muscle tumor,and nerve sheath tumor.Histologic mimics with myxoid stroma include myxoma and aggressive angiomyxoma.Molecular alterations that have been described in a subset of PF may be seen in gastroblastoma and malignant epithelioid tumor with gliomaassociated oncogene homologue 1(GLI1)rearrangement.The recent increase in publications on PF reflects growing recognition of this entity with expansion of clinical and pathologic findings in these cases.Herein we provide a review of PF in comparison to other mesenchymal tumors with histologic and molecular resemblance to raise the awareness of this enigmatic neoplasm.Also,we highlight the challenges pathologists face when the sample is small,or such rare entity is encountered intraoperatively.

Hepatic Langerhans cell histiocytosis:A review

Hepatic Langerhans cell histiocytosis(LCH)is characterized by proliferation and accumulation of Langerhans cells in the liver,causing liver dysfunction or forming a mass lesion.The liver can be involved in isolation,or be affected along with other organs.A common clinical hepatic presentation is cholestasis with pruritis,fatigue and direct hyperbilirubinemia.In late stages,there may be hypoalbuminemia.Liver biopsy may be required for the diagnosis of hepatic LCH.Histologic finding may be diverse,including lobular Langerhans cell infiltrate with mixed inflammatory background,primary biliary cholangitis-like pattern,sclerosing cholangitis-like pattern,and even cirrhosis at later stages.Because of its non-specific injury patterns with broad differential diagnosis,establishing a diagnosis of hepatic LCH can be challenging.Hepatic LCH can easily be missed unless this diagnosis is considered at the time of biopsy interpretation.A definitive diagnosis relies on positive staining with CD1a and S100 antigen.Liver involvement is a high risk feature in LCH.The overall prognosis of hepatic LCH is poor.Treating at an early stage may improve the outcome.Systemic chemotherapy is the mainstay of treatment and liver transplantation may be offered.New molecular markers involved in pathogenesis of LCH are being explored with a potential for targeted therapy.However,further studies are needed to improve outcome.

Benign vs malignant pancreatic lesions: Molecular insights to an ongoing debate

Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis,and paraduodenal pancreatitis can present as mass lesions and may mimicpancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thoroughhistologic examination with attention to certain morphologic features can assist indeciphering neoplastic from reactive, however small biopsies often remain achallenge. Variable histologic patterns in conventional PDAC may also confoundthe diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such asadenosquamous and squamous cell carcinoma, colloid carcinoma, medullarycarcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitateexcluding metastasis from other sites prior to rendering the diagnosis ofpancreatic carcinoma. The use of immunohistochemical staining and molecularmarkers can aid in separating benign from malignant and PDAC from metastasis.PDAC expresses a few non-specific epithelial and mucin immunomarkers such asCK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemicalmarker that is specific for PDAC in the right clinical context is SMAD4.Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDACin a limited sample. Unfortunately, this finding is seen only in 50% of PDACcases. The identification of certain mutations can help support a diagnosis ofPDAC when benign conditions are in the differential. At the molecular level,KRAS oncogene mutations are seen in approximately 93% of PDACs. Subsequentneoplastic progression is driven by additional mutations of tumor suppressorgenes, such as CDKN2A, TP53, and SMAD4. Molecular markers can also providean insight to the prognosis. For instance, the loss of SMAD4 is associated with apoor outcome whereas mutations in MLL, MLL2, MLL3, and ARID1A are associatedwith improved survival.

Composite intestinal adenoma-microcarcinoid:An update and literature review

Composite intestinal adenoma-microcarcinoid(CIAM)is a rare intestinal lesion consisting of conventional adenoma and small,well differentiated carcinoid[microcarcinoid(MC)]at its base.The incidence of CIAM is 3.8%in surgically resected colorectal polyps.While its pathogenesis is unknown,studies support the role of Wnt/β-catenin pathway in the tumorigenesis of CIAM.CIAMs have been primarily reported in the colon wherein they present as polyps with well-defined margins,similar to conventional adenomatous polyps.MC is usually found in adenomatous polyps with high-risk features such as large size,villous architecture,or high grade dysplasia.Histologically,the MC component is often multifocal and spans 3.9 to 5.8 millimeters in size.MC is usually confined within the mucosa but occasional CIAM cases with MC extending to the submucosa have been reported.MC of CIAM demonstrates bland cytology and inconspicuous proliferative activity.The lesional cells are positive for synaptophysin and 60%to 100%of cases show nuclearβ-catenin positivity.MC poses a diagnostic challenge with its morphologic and immunohistochemical resemblance to both benign and malignant lesions,including squamous morules/metaplasia,adenocarcinoma,squamous cell carcinoma,sporadic neuroendocrine tumor and goblet cell adenocarcinoma.CIAM is an indolent lesion with a favorable outcome.Complete removal by polypectomy is considered curative.Awareness and recognition of this rare entity will help arrive at correct diagnosis and improve patient care.Currently,CIAM is not recognized as a subtype of mixed neuroendocrine-nonneuroendocrine neoplasm by WHO.

Differential diagnosis and management of immune checkpoint inhibitor-induced colitis: A comprehensive review

Immune checkpoint inhibitors(ICIs)are a new class of cancer pharmacotherapy consisting of antibodies that block inhibitory immune regulators such as cytotoxic T lymphocyte antigen 4,programmed cell death 1 and programmed death-ligand 1.Checkpoint blockade by ICIs reactivates a tumor-specific T cell response.Immune-related adverse events can occur in various organs including skin,liver,and gastrointestinal tract.Mild to severe colitis is the most common side effect with some experiencing rapid progression to more serious complications including bowel perforation and even death.Prompt diagnosis and management of ICI-induced colitis is crucial for optimal outcome.Unfortunately,its clinical,endoscopic and histopathologic presentations are non-specific and overlap with those of colitis caused by other etiologies,such as infection,medication,graftversus-host disease and inflammatory bowel disease.Thus,a definitive diagnosis can only be rendered after these other possible etiologies are excluded.Sometimes an extensive clinical,laboratory and radiologic workup is required,making it challenging to arrive at a prompt diagnosis.Most patients experience full resolution of symptoms with corticosteroids and/or infliximab.For ICI-induced colitis that is treatment-refractory,small scale studies offer alternative strategies,such as vedolizumab and fecal microbiota transplantation.In this review,we focus on the clinical features,differential diagnosis,and management of ICIinduced colitis with special attention to emerging treatment options for treatmentrefractory ICI-induced colitis.