Liver transplantation and cirrhotomimetic hepatocellular carcinoma: classification and outcomes.

Liver transplantation has become the standard-of-care treatment for hepatocellular carcinoma (HCC) that falls within certain size and numerical criteria for patients with cirrhosis. Cirrhotomimetic (CMM) HCC is an uncommon growth pattern that infiltrates cirrhotic parenchyma, can become extensive in size, and can evade detection via radiological studies. Liver transplant outcomes for this type of HCC are not well reported but generally are considered to be poor. We wished to better describe this variant of HCC in explanted livers, derive a classification system for this tumor type, and assess the outcomes of liver transplantation for this tumor variant. All patients undergoing transplantation for HCC at a single center in 1996-2009 (358 patients) were retrospectively analyzed, and 26 patients exhibiting a CMM growth pattern were identified. We developed a classification system for this tumor growth pattern variant and determined patient and tumor-specific outcomes. We derived a classification schema for CMM HCC based on the tumor extent and cellular histopathology, with a clear cell pathology being associated with favorable outcomes. We noted 100.0% 3-year recurrence-free survival and 58.3% 5-year recurrence-free survival after transplantation for those patients with tumors confined to 1 lobe that had a clear cell pathology and 16.2% 3- and 5-year recurrence-free survival for those patients who did not meet these criteria. In conclusion, CMM HCC features were noted in 7% of the patients undergoing transplantation for HCC at our center, with favorable outcomes observed for inpatients with clear cell histology and growth involving less than or equal to 50% of the liver.

In situ hybridization for Coccidioides immitis 5.8S ribosomal RNA sequences in formalin-fixed, paraffin-embedded pulmonary specimens using a locked nucleic acid probe: a rapid means for identification in tissue sections.

Coccidioides immitis/Coccidioides posadasii are common causes of pulmonary infection in certain geographic areas, and are highly infectious when working with culture isolates in the laboratory. Rapid techniques to accurately identify this pathogen in tissues may be of benefit for diagnosis and in limiting the exposure of laboratory personnel to this agent. Locked nucleic acids (LNA) are modified nucleotides in which a ribonucleoside is linked between the 2'-oxygen and the 4'-carbon atoms with a methylene unit. LNA oligonucleotides exhibit increased thermal stability and make excellent probes for in situ hybridization (ISH). In this study, ISH utilizing a biotin-labeled LNA probe targeting Coccidioides sp. ribosomal RNA sequences in 6 formalin-fixed, paraffin-embedded pulmonary tissue specimens from 6 patients with culture positive or histologic findings suggestive of Coccidioides sp. infection is described. The cultures of the pulmonary specimens confirmed C. immitis in 3 of 6 patients. The ISH procedure with the LNA probe was positive in all 6 cases, although the number of organisms that were highlighted varied from rare to numerous. ISH with a biotin-labeled DNA probe of the same sequence was positive in 4 of the 6 cases and the signal intensity and number of organisms was much less than that observed with the LNA probe. Negative control tissues containing a variety of different fungal pathogens including Aspergillus sp., Fusarium sp., Blastomyces dermatitidis, Candida sp, Histoplasma capsulatum, and Zygomyces did not hybridize with the LNA and DNA probes. ISH with an LNA oligonucleotide probe targeting Coccidioides sp. ribosomal RNA is useful for rapid ISH. ISH could be rapidly performed when fungal pathogens are observed in tissue but cultures are negative or have not been performed.

Diagnostic utility of mucin profile in fine-needle aspiration specimens of the pancreas: an immunohistochemical study with surgical pathology correlation.

BACKGROUND: The cytologic differentiation between neoplastic and reactive/reparative processes in the endoscopic ultrasound-guided fine-needle aspirations (EUS-FNA) of the pancreas can be difficult. Malignant transformation of the pancreatic ductal epithelium changes the expression of apomucins. The goal of the current study was to determine an optimal immunohistochemical panel of mucin (MUC) antibodies that would allow the cytomorphologic distinction of pancreatic ductal adenocarcinoma and its differentiation from reactive/reparative processes and inadvertently sampled gastric and duodenal mucosa. METHODS: Pancreatic EUS-FNA specimens performed on 351 patients were reviewed. Expression profiles of MUC1, 2, 5AC, and 6 were examined on 56 cell block sections and 26 follow-up pancreatectomy specimens. RESULTS: MUC1 and 6 expression was found in nonneoplastic pancreatic samples, whereas there was an absence of expression of MUC2 and 5AC. MUC2 was detected in mucosal goblets cells of the duodenum, MUC6 in Brunner glands, and MUC5AC in gastric foveolar cells. MUC5AC expression in differentiating ductal adenocarcinomas from benign conditions demonstrated better operating characteristics than either MUC1 or MUC6. The apomucin expression pattern both in cytology and follow-up surgical pathology specimens was similar. In surgical pathology specimens, the panel of 3 antibodies, MUC1+/MUC2-/MUC5AC+, was noted in 15 of 17 ductal carcinomas (88.2%). In nonneoplastic pancreatic tissue, the expression panel MUC1+/MUC2-/MUC5AC- was observed in 14 of 17 (82.4%) cases. In cytology specimens, the combination of MUC1+/MUC2-/MUC5AC+ was noted in 21 of 30 ductal carcinoma cases (70.0%), 3 of 6 atypical cases (50%), and 1 of 1 suspicious for malignancy cases (100%). The combination MUC1+/MUC2-/MUC5AC+ was not observed in any of the negative for malignancy or reactive cases (0 of 6). CONCLUSIONS: The most optimal panel for the diagnosis of ductal adenocarcinoma in both the EUS-FNA specimens is a panel including MUC1/MUC2/MUC5AC, whereas a panel of all 4 antibodies (MUC1, 2, 5AC, and 6) will in addition aid in differentiating inadvertently sampled normal/reactive duodenal and gastric epithelium from neoplastic pancreatic tissue.

Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era.

The potential for disease progression in patients awaiting liver transplantation for hepatocellular carcinoma (HCC) has encouraged many centers to employ pre-transplant radiofrequency ablation or chemoembolization in an attempt to control tumor burden while patients are on the wait list. Despite general acceptance by the transplant community, few objective data demonstrate pre-transplant treatment efficacy or improved post-transplant outcomes in HCC patients listed with Model for End-Stage Liver Disease (MELD) exception points. To evaluate the utility of pre-transplant therapy in the current MELD era, we retrospectively compared 31 treated patients (T) with 33 untreated (U) controls. Study endpoints included patient and disease-free survival, tumor recurrence, explant tumor viability, and the ability of MRI to detect viable tumor after therapy. Both cohorts had similar demographic, radiographic, and pathologic characteristics, although untreated patients waited longer for transplantation [119 (U) vs. 54 (T) days after MELD assignment, (P = .05); range: 1 day to 21 months]. Only 20% of treated tumors demonstrated complete ablation (necrosis) as defined by histologic examination of the entire lesion. Only 55% of lesions with histologic viable tumor were detected by MRI after pre-transplant therapy. After 36 months of follow-up, there was no difference between the treated and untreated groups in overall survival (84 vs. 91%), disease free survival (74% vs. 85%), cancer recurrence (23% vs. 12%), or mortality from cancer recurrence (57% vs. 25%) (P > 0.1). In conclusion, viable tumor frequently persists after pre-transplant locoregional therapy, and neoadjuvant treatment does not appear to improve post-transplant outcomes in the current MELD era.

Appendicitis among liver transplant recipients.

Appendicitis among liver transplant recipients has not been described in the current literature. We report 8 recipients who experienced appendicitis three weeks to 181 months after liver transplantation (LT). Initial presenting findings differed from the nonimmunosuppressed population in that a majority of the patients did not have leukocytosis (>10,000 cells/mm3). Four patients experienced perforation, three of whom presented three days after the development of abdominal pain. All patients recovered after surgery without untoward sequela.