Case report and literature analysis: pancreatic hepatoid carcinoma with multiple lymph node metastases progressing to liver metastasis after pancreaticoduodenectomy.

Hepatoid carcinoma is an extrahepatic primary tumor displaying characteristics reminiscent of hepatocellular carcinoma differentiation, which is found in various organs, such as the stomach, ovaries, gallbladder, and pancreas. Reports of pancreatic hepatoid carcinoma remain scarce. Consequently, understanding of this disease remains a priority, with no established consensus on its diagnosis and management. Here, we reported the case of a 45-year-old woman diagnosed with hepatoid carcinoma located in the pancreatic head, accompanied by multiple lymph node metastases. Following pancreaticoduodenectomy, the patient developed liver metastases within 3 months. Subsequently, she underwent adjuvant therapy consisting of Teysuno and Durvalumab following microwave ablation for the liver metastases. Remarkably, the patient has survived for one year without significant disease progression. This case underscores the potential efficacy of immunotherapy as a promising treatment option for pancreatic hepatoid carcinoma. Further research and clinical trials are warranted to explore the optimal management strategies for this rare and challenging malignancy.

Focal Hepatocellular Carcinoma in Pancreas.

A 67-year-old man was found to have a pancreatic head mass on abdominal ultrasound. He had compensated liver cirrhosis due to hepatitis C. The fine-needle aspiration (FNA) biopsy of the mass reported an adenocarcinoma of the pancreas, while the subsequent histopathology report of the supraclavicular lymph node showed features of hepatocellular carcinoma (HCC). A second read and additional stains on the FNA specimen confirmed a hepatoid (hepatocellular) carcinoma of the pancreas. He received atezolizumab and bevacizumab and had a good response. Tumors with features of HCC outside of the liver rarely occur and even more rarely in pancreas, with less than 50 cases reported so far. Pure HCC-like morphology is the most common histological form among four subtypes and has a relatively better prognosis. Surgical resection is considered the treatment of choice if amenable and variable outcomes are reported with different chemotherapies. Challenges exist in the diagnosis and the management of this rare and intriguing entity, and the potential misdiagnosis can have grave consequences as the management is completely different for a pancreatic adenocarcinoma and hepatoid carcinoma. We report a case with a challenging diagnosis of metastatic pancreatic hepatoid carcinoma which was treated as unresectable HCC with immunotherapy and the patient had a good response.

A Rare and Difficult Diagnosis: A Case of Hepatoid Carcinoma of the Gallbladder.

Extrahepatic metastasis of hepatocellular carcinoma is usually associated with extensive intrahepatic lesions. Hepatoid adenocarcinoma is a rare variant of extrahepatic malignant adenocarcinoma that exhibits remarkable histological and immunohistochemical similarity to hepatocellular carcinoma, which can result in an underestimated diagnosis. This case report describes a patient with a newly found gallbladder polyp. Following cholecystectomy, the initial histological and immunohistochemical evaluation suggested a metastasis of hepatocellular carcinoma. However, after multiple scans, no primary intrahepatic lesion was found. A subsequent review of the gallbladder specimens showed negative staining for CK7 and CK19, leading to a diagnosis of hepatoid carcinoma of the gallbladder.

SALL4 as an indicator for the diagnosis of hepatoid carcinoma of the ovary: A case report and literature review.

Key Clinical Message: Primary HCO is a rare, aggressive ovarian malignant tumor, morphologically resembling HCC. SALL4 can be adopted to differentiate HCO from HCC. The serum AFP and CA125 rather than HE4 can be employed as possible biomarkers to track treatment and monitor recurrence. Abstract: We report a case of a postmenopausal woman presenting with lower abdominal pain and vaginal bleeding. She went through a maximal debulking surgery, and the pathological biopsy revealed hepatoid carcinoma of the ovary (HCO). Immunohistochemical assay demonstrates SALL4 as an indicator to differentiate HCO from hepatocellular carcinoma (HCC).

[Differential diagnostic between hepatocellular carcinoma and hepatoid carcinoma with bone metastasis revelation: What tools can be used?] / Diagnostic différentiel entre un carcinome hépatocellulaire et un carcinome hépatoïde à révélation métastatique osseuse : quels outils sont à disposition ?

Bone metastases of hepatocellular carcinoma (HCC) are rare and disease-revealing bone metastasis are exceptional. Here, we report the case of a 69-year-old man with a cervical vertebral metastasis of hepatocellular carcinoma. Morphological aspect of a metastatic tumor with eosinophilic and polygonal cells raises the question of the differential diagnosis between a localization of a hepatocellular carcinoma or an hepatoid carcinoma, notably when the metastasis is the first clinical manifestation. The morphological aspect by itself does not provide strong enough arguments for diagnosis. Well selected immunohistochemical markers can sometimes help to orientate towards one of the two hypotheses, in particular SALL4 and LIN28 which are in favour of hepatoid carcinoma when both are positive. Finally, as these two entities have different molecular profiles, molecular study can also be helpful to distinguish them. Indeed, HCCs often present TERT promoter, CTNNB1 mutations and IL-6/JAK/STAT pathway activation while hepatoid adenocarcinoma frequently presents chromosome 20 long arm gain. TP53 mutations are found in both entities and are therefore not discriminating. Differential diagnosis is important because the treatment will be that of the primary. Prognostic data for HCC revealed by bone metastasis are scarce, although they seem to be associated with a poor prognosis, with a 1 to 2 months overall survival. There is currently no data for hepatoid adenocarcinoma with bone metastasis.

Hepatoid prostatic carcinoma with adrenal metastasis and novel genetic alterations.

Hepatoid carcinoma (HC) encompasses epithelial extrahepatic tumors exhibiting features of hepatocellular carcinoma (HCC) both by morphology and immunohistochemistry. Distinguishing metastatic HCC from HC may be challenging, particularly when limited material, such as a cytologic specimen, is available. HC from prostatic origin is unusual and has only rarely been characterized by cytology. Herein we present an 86-year-old male with history of castration-resistant prostate cancer developing a left adrenal gland nodule. Fine needle aspiration revealed a poorly differentiated malignant neoplasm diagnosed as metastatic hepatoid prostatic adenocarcinoma based on immunohistochemistry (positive for HepPar1, AFP, NKX3.1, PSMA, and Racemase; and negative for CK7, CK20, cytokeratin 34betaE12, p63, and Arg-1). Because prostatic carcinoma with hepatoid features is rare, and the patient had failed standard therapy, next generation sequencing was performed in an attempt to identify druggable molecular targets. Well-known prostate carcinoma-related alterations were found in three genes (CDK12, AR, and SPOP). In addition, three variants of uncertain significance (DDR2 R128C, SRC P428L, and HNRNPU K574Sfs*32) were identified, which to the best of our knowledge have not been previously reported. Our results support the power of an immunohistochemistry panel including Arg-1 and HepPar1 when HC is suspected, and highlight the value of cytology for comprehensive diagnostic evaluation.

Hepatoid carcinoma and related entities of the extrahepatic bile duct: A clinicopathological study of four cases.

Hepatoid carcinoma or related entities (HPC/RTs) are extremely rare, especially in the extrahepatic bile duct (EHBD). Only a few case reports have been published. We analyzed the clinicopathological features of HPCs/RTs in EHBD. HPC/RT of extrahepatic cholangiocarcinoma (eCCA) cases were selected based on the histological characteristics and immunohistochemical detection of spalt-like transcription factor 4 (SALL4) and/or alpha-fetoprotein (AFP). Four HPC/RT cases arose in the distal but not in the perihilar EHBD. The four patients with HPC/RT included one female and three males with a median age of 77 years. There are various macroscopic types of HPC/RT. The predominant histological features were two solid-type carcinomas that mimicked hepatocellular carcinoma and two well-differentiated tubular adenocarcinomas. Immunohistochemically, SALL4 and glypican-3 were expressed in all cases, and AFP was expressed in one case. Cancer cell phenotypes included intestinal, pancreatobiliary, and mixed pancreatobiliary and intestinal types. Focal neuroendocrine differentiation and severe perineural and lymphovascular invasions were also observed. HPC/RT recurred in two patients within 2 years, and one patient died 13 months postoperatively. It is suggested that the HPC/RT of EHBD shares common characteristics with HPC/RT arising in various organs, and has some unique characteristics. HPC/RT of EHBD might be more aggressive than conventional eCCA.

Dedifferentiation-like tubular and solid carcinoma of the stomach shows phenotypic divergence and association with deficient SWI/SNF complex.

Gastric carcinoma showing an abrupt transition from a tubular to solid pattern is an unusual phenomenon reminiscent of dedifferentiation. The phenotypic and molecular characteristics of this transition are still unclear. We retrospectively collected 41 gastric carcinomas exhibiting dedifferentiation-like tubular to solid transition and applied an array of immunohistochemical stains, including neuroendocrine and hepatocytic markers, to delineate their lineage. The status of Epstein-Barr virus (EBV) infections, mismatch repair proteins, SWI/SNF complex proteins and p53 expression levels were examined. The clinicopathologic differences were assessed by statistical analysis. Except for 10 cases with neuroendocrine differentiation and 2 EBV-associated carcinomas, we identified 8 hepatoid carcinomas and 21 solid adenocarcinomas with loss of CDX2 and/or hep-par1 expression in solid part (12/29). A subset of solid adenocarcinoma was associated with MSI (8) and mutant p53 expression was frequent in non-MSI cases (10/13). We found hepatoid carcinomas usually harbored SMARCA2 loss (5/8), MSI-associated cases commonly had ARID1A loss (6/8), and non-MSI solid adenocarcinomas frequently showed SMARCA2/A4 loss (7/13) with a high rate of concurrent ARID1A loss (4/7). Spatial correlation between solid transition and loss of SWI/SNF complex subunits were seen in 63% of tumors (12/19). Dedifferentiation-like tubular and solid carcinoma was associated with a propensity to inferior survival outcomes (p = 0.034), especially hepatoid carcinoma and in the non-MSI/EBV intestinal subgroup. In conclusion, gastric cancer exhibiting dedifferentiation-like tubular to solid transition is a phenotypically divergent group that shares common alterations in the SWI/SNF complex.

Research progress on pancreatic hepatoid carcinoma / 中华肝胆外科杂志

Pancreatic hepatoid carcinoma (PHC) is a rare neoplasm that shares differentiation features with hepatocellular carcinoma. It is a special type of adenocarcinoma which can be accompanied by elevated serum AFP. PHC is highly invasive, and has a poor prognosis, and it usually present with vascular invasion, liver and/or lymph node metastasis. Preoperative diagnosis of PHC is difficult, and there is currently no consensus on its diagnosis and treatment. A better understanding of PHC is helpful to improve its diagnostic rate and to allow timely and effective application of treatment. This article reviews the research progress on PHC.

Surgical Resection of Pancreatic Hepatoid Carcinoma Followed by Combined Transarterial Chemoembolization and Immunotherapy: A Case Report.

Pancreatic hepatoid carcinoma (HC) is a heterogeneous tumor with high degree of malignancy and poor prognosis, which display cytological and/or structural features of focal hepatocellular carcinoma (HCC). For the low incidence and atypical clinical symptoms, it is possible to be diagnosed as pancreatic cancer before operation, and mainly depending on the pathological examination. To the best of our knowledge, surgery combined with radiotherapy and chemotherapy is the common treatment of pancreatic HC. However, the curative effect and prognosis is poor. We report a case of 44-year-old woman with pancreatic HC treated with PD-1 receptor inhibitor and transarterial chemoembolization, whose clinical symptoms and laboratory indexes are significantly improved after treatment.

Mixed pancreatic hepatoid carcinoma: A surgical case report and literature review.

BACKGROUND: Hepatoid carcinoma (HC) is a rare type of malignant tumor that shared similar features of morphology and immunohistochemistry with hepatocellular carcinoma (HCC). Pancreatic HC exists as either pure or mixed type. Mixed pancreatic HC is extremely rare, with only a few cases reported in the literature to date. Because of the rarity of mixed pancreatic HC, its clinical features including incidence, characteristics, and prognosis remain unclear. We herein report a case of a 49-year-old man who was diagnosed with mixed pancreatic HC with neuroendocrine differentiation and was treated with pancreaticoduodenectomy and adjuvant chemotherapy. We also review the existing case reports in literature. PRESENTATION: A 49-year-old man was admitted to our hospital after a chronic abdominal pain in the upper right quadrant. Abdominal ultrasound revealed only one low-density retroperitoneal mass measured at 20 × 48mm in size in the pancreatic-duodenal junction, whereas contrast-enhanced computed tomography (CT) revealed three lymphatic neoplasms measured at 28 × 22 × 30 mm, 27 × 33 × 38 mm and 22 × 35 × 48 mm in size in the retroperitoneal pancreatic-duodenal junction. Ultrasound-guided tumor biopsy was performed. Pathological reading of tumor biopsy suspected of Paraganglioma/pheochromocytoma. Laparotomic retroperitoneal tumoral resection and lymphadenectomy was then performed. Histological reading was lymphatic metastasis of primary pancreatic hepatocellular carcinoma with neuroendocrine differentiation, which were immunohistochemically positive for CKAE1/AE3, Hepatocyte paraffin 1, Chromogranin. After three weeks of the first surgery, the patient was assigned with Positron Emission Tomography - Computed Tomography (PET-CT) before adjuvant chemotherapy, revealing a low-density high-metabolism mass, 26 × 28 mm in size within the parenchyma of pancreatic head. Laparotomic pancreaticoduodenectomy and standard lymphadenectomy was performed to resect one mass, which revealed the same immunohistology features with the first mass. The patient was followed up with FOLFIRINOX protocol, and after 12 cycles, there was no evidence of postoperative recurrence. DISCUSSION: There are few reported cases describing pancreatic hepatoid carcinoma, especially mixed form with other histological associated component. Neuroendocrine differentiation is the majority associated component with 62.5% of all cases of mixed - type form. CONCLUSION: Primary pancreatic hepatocellular carcinoma with neuroendocrine differentiation was rare, biopsy and immunohistochemistry appeared with high diagnostic value in this case. The prognosis of pancreatic HC depends on the extent and tumor eradication, and in this case we recorded no postoperative complications and no recurrence in the 6-month follow-up period.

Hepatoid thymic carcinoma: a case report of a rare subtype of thymic carcinoma.

Hepatoid thymic carcinoma is an extremely rare subtype of primary thymus tumor resembling "pure" hepatoid adenocarcinomas with hepatocyte paraffin 1 (Hep-Par-1) expression. A 53-year-old man presented with voice change and a neck mass. Multiple masses involving the thyroid, cervical and mediastinal lymph nodes, and lung were detected on computed tomography. Papillary thyroid carcinoma was confirmed by biopsy, and the patient underwent neoadjuvant chemoradiation therapy. However, the anterior mediastinal mass was enlarged after the treatment whereas the multiple masses in the thyroid and neck decreased in size. Microscopically, polygonal tumor cells formed solid sheets or trabeculae resembling hepatocytes and infiltrated remnant thymus. The tumor cells showed immunopositivity for cytokeratin 7, cytokeratin 19, and Hep-Par-1 and negativity for α-fetoprotein. Possibilities of germ cell tumor, squamous cell carcinoma, and metastasis of thyroid papillary carcinoma were excluded by immunohistochemistry. This report on the new subtype of thymic carcinoma is the third in English literature thus far.

Mimics of hepatocellular carcinoma: a review and an approach to avoiding histopathological diagnostic missteps.

Hepatocellular carcinoma (HCC) is one of the commonest carcinomas and leading causes of cancer-related death. Although, in patients with cirrhosis, radiologic diagnosis has improved significantly over the years, needle biopsy and histopathological assessment remains an important diagnostic modality. Most importantly, histopathological diagnosis is essential in patients with contending extrahepatic primaries, those with no known HCC risk factors, patients with ambiguous radiological features, and many other clinical contexts. Helpful features such as high serum alpha-fetoprotein (AFP) serologies are known to be present in many other tumor (including but not only HCC) and nontumor contexts and therefore not only lack sufficient diagnostic specificity for HCC but also create the potential to overlook non-HCC AFP-producing tumors, of which there are many. Therefore, using clinical examples and other examples from the medical literature, this review discusses several clinical and histological mimics of HCC and proffers an approach for practicing pathologists geared toward avoiding missteps.

Hepatoid adenocarcinoma of the lung mimicking metastatic hepatocellular carcinoma.

Hepatoid adenocarcinoma of the lung is a rare subtype of lung cancer. We report a case of a metastatic hepatoid adenocarcinoma of the lung with aggressive behavior, including biopsy and autopsy findings. The pulmonary tumors showed features indistinguishable from hepatocellular carcinoma and were diffusely positive for Hepatocyte Paraffin 1.

High-grade serous carcinoma of fallopian tube with yolk sac tumor differentiation in a postmenopausal patient.

Yolk sac tumors (YSTs) are the second most common germ cell malignancy of the ovaries, generally presenting in children and young women. However, they rarely occur in the fallopian tubes of postmenopausal patients. The current rare case is composed of yolk sac tumor differentiation within high-grade serous carcinoma (HGSC) arising in the fallopian tube of a 68-year-old woman. Serum α-fetoprotein was much higher than normal level. This case exhibited some areas of glandular architecture with positivity for SALL4, AFP, and Glypican-3 and negative staining for PAX8, supporting a germ cell tumor differentiation. By reviewing the published literature, we believe that YSTs, whether or not associated with an epithelial component detected histologically in older patients, constitute a single entity that is different from YSTs in younger patients. Above all, the pathologist must check carefully tissue stained with hematoxylin-eosin especially in postmenopausal women with ovarian, fallopian tube, or endometrial mass and an elevated serum α-fetoprotein level. Neoplasms of this type should be treated aggressively, and should respond to platinum-based chemothotherapy.

Hepatoid adenocarcinoma of the lung mimicking metastatic hepatocellular carcinoma

Hepatoid adenocarcinoma of the lung is a rare subtype of lung cancer. We report a case of a metastatic hepatoid adenocarcinoma of the lung with aggressive behavior, including biopsy and autopsy findings. The pulmonary tumors showed features indistinguishable from hepatocellular carcinoma and were diffusely positive for Hepatocyte Paraffin 1.

Hepatoid carcinoma of the ovary - A case report and literature review.

We present the case of a 27-year old female with an ovarian tumor and alpha-fetoprotein (AFP) of 1210 ng/m, a right salpingo-oophorectomy was performed and had conservative complementary staging by gynecologic oncologists. The histopathological report was primary hepatoid carcinoma of the ovary (HCO), clinical stage IA, complementary treatment was adjuvant chemotherapy with BEP and remains clinical, imaging and biochemically disease free in three years follow up.

Hepatoid carcinoma of the pancreas: A case report and review of the literature.

BACKGROUND: Hepatoid carcinoma (HC) is an extremely rare neoplasm that is morphologically similar to hepatocellular carcinoma. HC has been described in various organs; however, HC of the pancreas is extremely rare. To our knowledge, only 38 cases have been reported. We present a case of HC of the pancreas in a 36-year-old male patient. CASE SUMMARY: A 36-year-old cachexic man with no significant past medical history was transferred to our hospital with a history of painless jaundice, elevated blood glucose and significant weight loss. Lab tests showed elevated serum transaminases, bilirubin and alpha-fetoprotein levels. Magnetic resonance imaging of the upper abdomen showed a diffusely enlarged pancreas, appearing "sausage-shaped". Magnetic resonance cholangiopancreatography showed upstream ductal dilation secondary to stricture of the main pancreatic duct and the common bile duct, which were not visible. Immunohistochemistry of biopsied tissue from a percutaneous pancreatic biopsy showed tumor cell positivity for HepPar1, polyclonal carcinoembryonic antigen and CK19, suggestive of HC of the pancreas. The characteristics of 39 patients with HC of the pancreas were reviewed. CONCLUSION: HC of the pancreas is more prevalent in males, and patients have a median age of 57 years. It is most commonly asymptomatic or presents as abdominal back pain, and the pancreatic tail is the most common location. At the time of diagnosis, liver metastasis is often present.

Pure pancreatic hepatoid carcinoma: a surgical case report and literature review.

BACKGROUND: Hepatoid carcinoma (HC) is an extra-hepatic neoplasm that shares the morphological and immunohistochemical features of hepatocellular carcinoma. Pancreatic HC exists as either pure or combined type. Pure pancreatic HC is extremely rare, with only a few cases reported in the literature to date. Because of the rarity of pure pancreatic HC, its clinical features including incidence, behavior, and prognosis remain unclear. We herein report the case of a 56-year-old man who developed pure pancreatic HC treated with surgical resection. We also include a review of the existing literature. CASE PRESENTATION: A 56-year-old male patient was admitted to our hospital after a pancreatic cyst was identified by abdominal ultrasonography on a comprehensive medical examination. Endoscopic ultrasound revealed a cystic mass measuring 13 mm in size in the pancreatic head and a low-density mass measuring 16 mm in size in the pancreatic tail, which was partially enhanced on contrast-enhanced ultrasound. Contrast-enhanced computed tomography (CT) revealed a branch duct type intraductal papillary mucinous neoplasm in the pancreatic head and an early enhanced nodule measuring approximately 10 mm in size in the pancreatic tail. Endoscopic ultrasound-guided fine-needle aspiration of the hypervascular tumor was performed. The hypervascular tumor was suspected to be a solid pseudopapillary neoplasm. Laparoscopic spleen-preserving distal pancreatectomy was performed. Histology was identical to hepatocellular carcinoma of the liver. Immunohistochemically, the tumor cells were positive for hepatocyte paraffin 1, and a canalicular pattern was confirmed on the polyclonal carcinoembryonic antigen staining. The patient was diagnosed with a moderately differentiated pancreatic HC. The patient was followed up without adjuvant chemotherapy, and there was no evidence of recurrence at 6 months post-operatively. CONCLUSIONS: We present a case of moderately differentiated pure pancreatic HC. For the accurate preoperative diagnosis of pure pancreatic HC, biopsy is preferred to cytology or preoperative imaging studies such as CT. The prognosis of pure pancreatic HC depends on its differentiation.