Romano Colombari

Hepatic angiomyolipoma - A clinicopathologic study of 30 cases and delineation of unusual morphologic variants

Hepatic angiomyolipoma (AML) is frequently misdiagnosed. HMB-45 is a promising immunomarker for this tumor that leads to recognition of some AMLs with unusual morphology. The purpose of this collaborative study is to better define the morphologic variations of AML. Thirty AMLs were examined, including four biopsy specimens and two fine-needle aspirates. The diagnosis was confirmed by the presence of HMB-45-positive myoid cells. Almost half the cases were originally misdiagnosed as carcinomas or sarcomas. There was marked female predominance (25:5), and the mean age was 48.7 years (range 29-68). Three patients (10%) had evidence of tuberous sclerosis and all had renal AML. According to the line of differentiation and predominance of tissue components, the tumors was subcategorized into mixed, lipomatous (> or = 70% fat), myomatous (< or = 10% fat), and angiomatous type. The mixed type was the most common (11 resected cases), comprising sheets of epithelioid muscle cells admixed with islands of adipocytes, abnormal vessels, and frequently, hematopoietic cells. Six tumors (including three from biopsy specimens) were heavily fatty and showed predominantly adipocytes with epithelioid and short spindle myoid cells webbed between fat cells. Of 10 myomatous AMLs, five tumors showed a pure sinusoidal trabecular pattern and comprised mainly epithelioid cells. Typically, mature adipocytes were absent or scanty, but fat was seen as fine droplets within cytoplasm or as occasional large globules in sinusoids. Pelioid and inflammatory pseudotumor-like patterns were identified focally. Regarding cellular features of the myoid cells, most of the epithelioid cells were either eosinophilic or clear with spiderweb cell morphology. Three AMLs showed an almost purely oncocytic appearance with scanty fat. Large pleomorphic epithelioid cells existed as small foci. Spindle cells arranged in long fascicles were uncommon. D-PAS-positive globules were common around pelioid areas. Brown pigments with staining characteristics of hemosiderin and/or melanin were noted. In conclusion, we propose HMB-45-positive myoid cells as the defining criterion of hepatic AML, which is a tumor capable of dual myomatous and lipomatous differentiation and melanogenesis. Because of its protean morphologic appearance, recognition of the various variant patterns and cell types is important for a correct diagnosis, assisted by immunohistochemical confirmation with HMB-45. Trabecular and oncocytic cell tumors appear to stand out as distinctive subtypes.

The Perivascular Epithelioid Cell and Related Lesions

Summary A family of lesions composed of a newly characterized and distictive cell type, called perivascular epithelioid cell (PEC), has been identified. This cell type characteristically shows immunoreactivity with the melanogenesis-marker HMB45. In this review, we summarize the rapidly growing data on this cell type and its related lesions. These lesions can occur in many different organs, are closely related lo the tuberous sclerosis complex, and can show loss of heterozygosity in TSC1 or TSC2 regions. These lesions include: angiomyolipoma (AML) and its monotypic variants (leiomyoma-like AML, lipoma-like AML, oncocyloma-like AML, monolypic epithelioid AML), pulmonary and extrapulmonary clear cell “sugar” tumor, lymphangiomyoma, lymphangioleiomyomatosis, and renal capsuloma

Distribution of melanoma specific antibody (HMB-45) in benign and malignant melanocytic tumours. An immunohistochemical study on paraffin sections.

The distribution of a recently produced melanoma specific antibody (HMB-45) has been evaluated histochemically on paraffin sections in a large panel of melanocytic and non melanocytic tumours. Results have been compared with the presence of S-100 protein. HMB-45 was shown to be a highly specific antibody being present only in melanomas, junctional melanocytes and histogenetically related neoplasms such as melanocytic neuroectodermal tumour of infancy and, at low levels, on a proportion of peripheral nerve sheath tumours. The high specificity of HMB-45 antibody, coupled with the greater sensitivity of S-100, makes the combined use of these markers practical in the differential diagnosis of skin tumours and of metastatic lesions of uncertain primary site.

α-Interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers

Forty patients with chronic viral hepatitis or active cirrhosis (33 anti-HCV positive) entered a recombinant human alpha 2A interferon randomized trial. Twenty-one subjects were treated with 6 million units (MU) three times per week for 6 months. Nineteen were not treated. Six months later in 12 patients of the treated group (60% of the evaluable 20) with normalized serum aminotransferases levels (responders), fibrogenesis serum markers (NPIIIP and laminin) were significantly lower than baseline. In the untreated patients and in non-responders NPIIIP and laminin were unchanged. Semi quantitative histological evaluation (allotting scores for inflammation, necrosis and fibrosis) confirmed a significant improvement of necro-inflammation in the responders. These data suggest that alpha-IFN treatment may decrease stimuli for fibrogenesis by reducing liver inflammation and necrosis, thus preventing evolution to cirrhosis.

Small-cell neuroendocrine carcinoma of the ampullary region. A clinicopathologic, immunohistochemical, and ultrastructural study of three cases.

We report the clinicopathologic, immunohistochemical, and ultrastructural features of three small-cell neuroendocrine carcinomas of the ampullary region of the duodenum. All patients were men; their ages were 51, 62, and 66 years. The therapy consisted of pancreatoduodenectomy. All patients died of the disease; median survival was 10 months from the diagnosis. The histological appearance was identical to pulmonary and extrapulmonary small-cell carcinoma. The neuroendocrine differentiation was demonstrated ultrastructurally by the presence of dense-core granules, and by the positive immunoreaction for neuron-specific enolase and Leu-7 in each case. One case expressed a focal positivity for chromogranin A (PHE-5) and argyrophilic granules. The same case showed the presence of neurofilaments on frozen material. Neurofilament proteins could not be demonstrated in any case in paraffin sections. Neoplastic cells exhibited cytoplasmic immunostaining for cytokeratins (CAM 5.2) in all cases. In one case, a large number of neoplastic cells (60–70%) exhibited nuclear Ki-67 positivity. We postulate that the diseases histogenesis was from epithelial stem cell expressing both epithelial and neuroendocrine characteristics. The clinical behavior of small-cell neuroendocrine carcinomas of the ampullary region appears to be extremely aggressive, with early metastases and fatal outcome.

Chronic hepatitis in multiple virus infection : histopathological evaluation

The frequency and histological pattern of multiple hepatitis virus infection was studied in 161 Italian patients who had consecutively undergone liver biopsy from 1989 to 1991. The histological features were compared with that of infection with a single virus. Thirty‐nine per cent of patients had evidence of past or present multiple infection, the commonest of which was hepatitis C virus (HCV) in patients with evidence of previous infection with hepatitis B virus (HBV). In general, the severity of the histological pattern of each viral infection was maintained even when more than one virus was involved; there was neither exacerbation nor diminution of the histological changes. The δ‐5‐virus (HDV) was not associated with severe necro‐inflammatory lesions, but HDV‐positive patients were few in this cohort. Lymphoid follicle formation (a putative histological marker of HCV infection) was also found in a high proportion of HCV negative patients but expressing much HBcAg or HDAg in liver tissue. Possible explanations for this finding are that follicles are relatively non‐specific for HCV infection, or that these cases represent HCV infection with false‐negative serology. The results of this study suggest that multiple hepatitis virus infection is common in the population investigated and that HBV and HCV co‐infection cannot be reliably diagnosed histologically. Whether double infection with these viruses influences the cirrhotic evolution of the liver lesion remains unclear.

Tumor deposits are encountered in advanced colorectal cancer and other adenocarcinomas: an expanded classification with implications for colorectal cancer staging system including a unifying concept of in-transit metastases

The seventh edition of the TNM Classification of Malignant Tumors is due to be published soon. In the current version dating back to 2002, tumor deposits, which are metastatic lesions commonly encountered in the routine histopathological examination of advanced colorectal cancer specimens, are classified according to their shape with different implications for staging. So distinguished, these lesions are considered either as metastatic lymph nodes (N category) or as vascular invasions (T category). We recently proposed a more comprehensive classification approach that also includes the M category. Relying on two of our independent recent studies, we aim here to provide suggestions for a novel classification of tumor deposits with diverse implications for TNM staging system of colorectal cancer. Furthermore, we show that tumor deposits are not limited to colorectal cancer, but they are common to different adenocarcinoma types.

Serum laminin P1 in chronic viral hepatitis: correlations with liver histological activity and diagnostic value

Laminin is a major basement membrane-associated, non-collagenous glycoprotein of the extracellular matrix and is deposited in the space of Disse during sinusoidal capillarisation. Laminin P1, a pepsin-resistant fragment originating from the central portion of the cross-shaped laminin molecule, is detectable in serum and has been related to liver fibrosis and portal hypertension. In this study we investigated the behaviour of serum laminin P1, measured by radioimmunoassay, in a homogeneous group of 95 patients suffering from chronic viral hepatitis, types C or B, in order to determine the relationships between serum laminin P1 and each of the main histological aspects of the disease process (i.e. portal-periportal activity, lobular activity and fibrosis), which were assigned numerical scores. Moreover, we computed, at several cut-off levels, the sensitivity, specificity and positive and negative predictive values of laminin P1 in detecting both necroinflammatory activity and fibrosis in the liver. The results show that serum laminin P1 levels parallel the severity of liver disease, the highest laminin concentrations being observed in cirrhotic patients. They suggest also that serum laminin P1 should be considered a marker of the liver disease process as a whole, rather than a marker exclusively linked to fibrosis. Nevertheless, the usefulness of serum laminin P1 measurement, as investigated in this study, seems too limited to be recommended for routine clinical practice.

iPathology cockpit diagnostic station: validation according to College of American Pathologists Pathology and Laboratory Quality Center recommendation at the Hospital Trust and University of Verona

BackgroundValidation of digital whole slide images is crucial to ensure that diagnostic performance is at least equivalent to that of glass slides and light microscopy. The College of American Pathologists Pathology and Laboratory Quality Center recently developed recommendations for internal digital pathology system validation. Following these guidelines we sought to validate the performance of a digital approach for routine diagnosis by using an iPad and digital control widescreen-assisted workstation through a pilot study.MethodsFrom January 2014, 61 histopathological slides were scanned by ScanScope Digital Slides Scanner (Aperio, Vista, CA). Two independent pathologists performed diagnosis on virtual slides in front of a widescreen by using two computer devices (ImageScope viewing software) located to different Health Institutions (AOUI Verona) connected by local network and a remote image server using an iPad tablet (Aperio, Vista, CA), after uploading the Citrix receiver for iPad. Quality indicators related to image characters and work-flow of the e-health cockpit enterprise system were scored based on subjective (high vs poor) perception. The images were re-evaluated two weeks apart.ResultsThe whole glass slides encountered 10 liver: hepatocarcinoma, 10 renal carcinoma, 10 gastric carcinoma and 10 prostate biopsies: adenocarcinoma, 5 excisional skin biopsies: melanoma, 5 lymph-nodes: lymphoma. 6 immuno- and 5 special stains were available for intra- and internet remote viewing. Scan times averaged two minutes and 54 seconds per slide (standard deviation 2 minutes 34 seconds). Megabytes ranged from 256 to 680 (mean 390) per slide storage. Reliance on glass slide, image quality (resolution and color fidelity), slide navigation time, simultaneous viewers in geographically remote locations were considered of high performance score. Side by side comparisons between diagnosis performed on tissue glass slides versus widescreen were excellent showing an almost perfect concordance (0.81, kappa index).ConclusionsWe validated our institutional digital pathology system for routine diagnostic facing with whole slide images in a cockpit enterprise digital system or iPad tablet. Computer widescreens are better for diagnosing scanned glass slide that iPad. For urgent requests, iPad may be used. Legal aspects have to be soon faced with to permit the clinical use of this technology in a manner that does not compromise patient care.

Huge renal cyst with parietal renal cell carcinoma, osseous metaplasia and a papillary adenoma: a case report with unique clinicopathological features and literature review

The unique clinicopathological features of a giant solitary renal cyst with a parietal clear cell carcinoma in contiguity with a focus of osseous metaplasia and a papillary adenoma are reported. Ultrasonography and computed tomography showed a single cyst with a focal wall irregularity. During surgery, a frozen section revealed the presence of a renal cell carcinoma of clear cell type, so a nephrectomy was performed. After extensive pathological sampling of the cyst’s wall, a focus of osseous metaplasia in contiguity with the main tumour and a microscopic papillary adenoma were found. Diagnostic implications for the present case are discussed within a pertinent literature review.