Deborah Malvi

Oncocytic carcinoma arising in Warthin tumour

Sir, Warthin tumour (WT) of the parotid gland is by definition clinically benign, although on rare occasions it can give rise to malignant tumours, which originate from both the epithelial and lymphoid component. Among epithelial malignancies, mucoepidermoid carcinoma (MEC) [5] has been described in WT. This association is in keeping with the evidence that MEC is a “mitochondrion-rich” tumour, showing features of differentiation towards striated ducts [3]. Pure oncocytic cell carcinomas are a rarity in salivary glands and are thought to derive from the oncocytic epithelium of striated ducts. The purpose of the present paper is to report a case of oncocytic carcinoma (OC) arising in WT of parotid gland.

RUNX-1 and CD44 as markers of resident stem cell derivation in undifferentiated intimal sarcoma of pulmonary artery

Vasuri F, Resta L, Fittipaldi S, Malvi D & Pasquinelli G 
(2012) Histopathology 61, 737–743

Histopathological evaluation of recurrent hepatitis C after liver transplantation: A review

Although the morphological features of hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) have been well established in the last decades, the differential diagnosis still represents a challenge for the pathologist, especially early recurrent hepatitis C vs mild acute cellular rejection. The present review focuses on the role of the pathologist and the pathology laboratory in the management of recipients with recurrent hepatitis C, the usefulness of early and late post-OLT liver biopsies, and the potential role of ancillary techniques (immunohistochemistry and reverse transcription-polymerase chain reaction, RT-PCR). The English literature on the topic is reviewed, focusing on the histopathology, the immunohistochemistry and the use of RT-PCR on HCV-positive post-OLT biopsies. The different histopathological illustrations of early and chronic recurrent hepatitis C are presented, with special focus on the main differential diagnoses and those features with prognostic relevance (cholestasis above all). The usefulness of ancillary techniques are discussed, especially HCV RNA quantitation by RT-PCR. Finally, the usefulness of long-term protocol biopsies is addressed: their usefulness for the study of allograft disease progression is clear, but their meaning in the long term is still debated. The significance of plasma cell infiltrate in HCV-positive allografts, the prognostic weight of graft steatosis, and the impact of donor age in recurrent hepatitis C also represent additional open issues.

Real-time quantitative assay for routine testing of HCV RNA in formalin-fixed, paraffin-embedded liver samples.

The assessment of hepatitis C virus (HCV) RNA in liver tissues is clinically relevant in cases where histology, liver function tests, and HCV serology are not sufficient for a definitive diagnosis of HCV-related hepatitis. We analyzed 215 formalin-fixed, paraffin-embedded liver needle biopsies from patients infected with HCV genotypes 1b and 2. HCV RNA extracted from paraffin sections were quantified by means of a TaqMan real-time reverse transcription-polymerase chain reaction method. The quantification of HCV RNA in liver tissue was correlated with the amount of HCV detected by immunohistochemistry (IHC) on paired frozen biopsies, the HCV RNA load in the serum, and the main serum tests of liver function and cholestasis. HCV RNA was detected by real-time reverse transcription-polymerase chain reaction in 169 liver biopsies (78.6%) with a mean value of 13.59±37.25 IU/ng. Tissue HCV RNA levels strongly correlated with the IHC results (P<0.001, Spearman test), HCV serum load (P<0.001), aspartate aminotransferase (P=0.001), γ-glutamyl transpeptidase (P=0.012), and aspartate aminotransferase/alanine aminotransferase ratio (P=0.029). HCV RNA was amplified in up to 7-year-old archival tissue samples. Real-time HCV RNA quantification on archival liver tissue may be clinically relevant in case of “occult” HCV infection or for the diagnosis of patients with known HCV infection and hepatic dysfunction but seronegative for HCV RNA. The assessment of the levels of HCV RNA in the liver might also be important for monitoring the effectiveness of antiviral therapy and the progression of disease in patients with chronic HCV hepatitis.

Esophagogastric metaplasia relates to nodal metastases in adenocarcinoma of esophagus and cardia.

BACKGROUND Immunohistochemical profiles of esophageal and cardia adenocarcinoma differ according to the presence or absence of Barretts epithelium (BIM) and gastric intestinal metaplasia (GIM) in the fundus and antrum. Different lymphatic spreading has been demonstrated in esophageal adenocarcinoma. We investigated the correlation among the presence or absence of intestinal metaplasia in the esophagus and stomach and lymphatic metastases in patients who underwent radical surgery for esophageal and cardia adenocarcinoma. METHODS The mucosa surrounding the adenocarcinoma and the gastric mucosa were analyzed. The BIM+ patients underwent subtotal esophagectomy and gastric pull up, and the BIM- patients underwent esophagectomy at the azygos vein, total gastrectomy, and esophagojejunostomy. The radical thoracic (station numbers 2, 3, 4R, 7, 8, and 9) and abdominal (station numbers 15 through 20) lymphadenectomy was identical in both procedures except for the greater curvature. RESULTS One hundred ninety-four consecutive patients were collected in three major groups: BIM+/GIM-, 52 patients (26.8%); BIM-/GIM-, 90 patients (46.4%); BIM-/GIM+, 50 patients (25.8%). Two patients (1%) were BIM+/GIM+. A total of 6,010 lymph nodes were resected: 1,515 were recovered in BIM+, 1,587 in BIM-/GIM+, and 2,908 in BIM-/GIM- patients. The percentage of patients with pN+ stations 8 and 9 was higher in BIM+ (p=0.001), and the percentage of patients with pN+ perigastric stations was higher in BIM- (p=0.001). The BIM-/GIM- patients had a number of abdominal metastatic lymph nodes higher than did the BIM-/GIM+ patients (p=0.0001). CONCLUSIONS According to the presence or absence of BIM and GIM in the esophagus and cardia, adenocarcinoma correspond to three different patterns of lymphatic metastasization, which may reflect different biologic and carcinogenetic pathways.

Interpathologist concordance in the histological diagnosis of focal prostatic atrophy lesions, acute and chronic prostatitis, PIN, and prostate cancer

Epidemiological and biological evidence indicates a causal relationship between the presence of proliferative atrophic lesions and the development of prostatic intraepithelial neoplasia (PIN) and prostate cancer. The presence of inflammatory and atrophic lesions of the prostate is widely underestimated and they are not generally mentioned in pathology reports. We performed a histopathological concordance study among eight genitourinary specialists and seven generalist pathologists, using 116 histological slides of prostate lesions, including proliferative atrophic lesions, PIN, and cancer. The overall agreement between all possible pairs of reviewers was 80% for prostate cancer, 67% for PIN, and 49% for proliferative atrophic lesions. When using as gold standard the assessment of a single genitourinary pathologist, the mean agreement percentage increased to 97% for prostate cancer, 92% for PIN, and 72% for proliferative atrophic lesions.

Adenocarcinoma in Crohn’s disease: the pathologist’s experience in a tertiary referral centre of inflammatory bowel disease

Summary The aim of the present study is to describe the histological and mutational characteristics of a series of both large and small bowel adenocarcinomas in patients with Crohns disease from a tertiary referral centre of inflammatory bowel disease. Bowel adenocarcinoma was diagnosed in 11 (1.7%) of 660 consecutive patients submitted to surgery for histologically proven Crohns disease in 5 years. The following data were collected: tumour site, stage and grade, intracellular/extracellular mucin, lymphovascular invasion, immunohistochemistry for keratin 7, keratin 20 and CDX-2, mutation analyses of KRAS, B-RAF, PI3K and microsatellite instability. A strong predominance of male gender was observed (10/11). Four (36.4%) adenocarcinomas arose in the small bowel, five (45.4%) in the anus/rectum, and two (18.2%) in anastomosis. Furthermore, all cases of anorectal adenocarcinoma showed >50% of extracellular mucin, with associated KRAS mutations in three of five. No influence in cancer incidence by infliximab therapy was observed. Our series, one of the largest on the topic with immunomorphological and molecular deepening, showed that bowel adenocarcinomas in Crohns disease have an aggressive behaviour and a strong predominance of extracellular mucin. In surgical specimens from Crohns disease patients, mucinous-looking anal fistulas and ileal areas of adhesion/retraction should always be extensively sampled.

From large to small: The immunohistochemical panel in the diagnosis of early hepatocellular carcinoma

The aims of this study were to: validate the use of the immunohistochemical (IHC) markers glutamine synthetase (GS), glypican‐3 (GPC3), heat shock protein‐70 (HSP70) and enhancer of zeste homologue 2 (EZH2) in liver biopsies for the differential diagnosis between small hepatocellular carcinoma (HCC) and non‐neoplastic liver nodules, with special attention to <10‐mm nodules; and assess the actual sensitivity and specificity of the single markers, and their combination, in needle biopsies.

Revisiting the role of pathological analysis in transarterial chemoembolization-treated hepatocellular carcinoma after transplantation

AIM To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification. METHODS We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected. We finally considered 11 histological variables for each patient: total number of nodules, number of viable nodules, size of the major nodule, size of the major viable nodule, occurrence of microscopic vascular invasion, maximum Edmondsons grade, clear cell/sarcomatous changes, and the residual neoplastic volume. Survival data were computed by means of the Kaplan-Meier procedure and analyzed by means of the Cox proportional hazards model. The multivariate linear regression and a k-means cluster analysis were also used in order to compute the standardized histological score. RESULTS The total number of nodules, the residual neoplastic volume (the total volume of all evaluated nodules minus the necrotic portion) and the microvascular invasion entered the Cox multivariate hazard model with HCC recurrence as dependent variable. The histological score was therefore computed and a cluster analysis sorted recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates and 1.6%, 11.1% and 38.5% of tumor-related mortality respectively at the end of follow-up. CONCLUSION The histological score allows a reliable stratification of HCC recurrence risk, especially in those recipients found out to be beyond the Milan criteria after orthotopic liver transplantation (OLT).

Genomic profiles of primary and metastatic esophageal adenocarcinoma identified via digital sorting of pure cell populations: results from a case report

BackgroundWe report on a female patient who underwent primary radical resection for a stage 2B Her-2-positive Barrett’s-type esophageal adenocarcinoma (EAC). Despite Her-2 targeted therapy, her disease recurred and required repeated metastectomies.Case presentationDigital cell sorting and targeted sequencing of cancer sub-clones from EAC and metastases revealed a completely mutated TP53, whereas the sorted stromal cells were wild-type. Her-2 amplification was significantly lower in the metastases when the patient became therapy-resistant.ConclusionsThe mechanism of therapy resistance illustrated by this case could only be detected through accurate analysis of tumor sub-populations.Investigating tumor sub-populations of recurrent disease is important for adjusting therapy in recurrent EAC.