Ferdinando Giordano

Fine Needle Biopsy of Hepatocellular Carcinoma: Improvement in Diagnosis by Microhistology

Percutaneous liver biopsies with fine aspirating and cutting needles were performed under ultrasound guidance to diagnose hepatocellular carcinoma in 112 cases. All the specimens were examined partially with cytologic methods and partially with microhistology. Cytology established the diagnosis of hepatocellular carcinoma in 83 cases and of generic malignancy in 12, with 9 false-negatives and 8 inadequates. Microhistology established the diagnosis of hepatocellular carcinoma in 92 case and of generic malignancy in 2, with 3 false-negatives and 15 inadequates. In all, the combined retrieval rate was 98% with only 2 cases of inadequate material and the diagnosis of hepatocellular carcinoma was possible in 105 cases (93.7%).

Malignant mixed müllerian tumor of the uterus. Features favoring its origin from a common cell clone and an epithelial-to-mesenchymal transformation mechanism of histogenesis.

Aims and background Various histogenetic mechanisms have been postulated to explain the biphasic carcinomatous-sarcomatous appearance of malignant mixed müllerian tumors (MMMTs), but the nature of these uncommon neoplasms is still unclear. Some evidence would suggest that MMMT displays similarities with sarcomatoid carcinoma, a tumor arising in extragenital sites that also features a mixed appearance. To gain further insight into the histogenesis of this tumor, we have studied by immunohistochemistry a case of uterine MMMT showing an extensive rhabdomyosarcomatous component. Methods A panel of antibodies including reactivity for p53, cytokeratin, vimentin, desmin, muscle actin, epithelial membrane antigen (EMA), myoglobin, type IV collagen, laminin, and tenascin was applied to paraffin tumor sections by means of the avidin-biotin complex technique. Results p53 immunoreactivity was observed in approximately the same number of cells in carcinomatous and sarcomatous tissue. The former stained for vimentin, cytokeratin and EMA, while the latter, in addition to expressing vimentin, desmin, muscle actin and myoglobin, also exhibited immunoreactivity for epithelial markers such as cytokeratin and EMA. At the borders between carcinoma and sarcoma the basement membrane pattern, as seen by staining for type IV collagen and laminin, showed interruptions in correspondence with areas of transition between the two tissues. Antibody to tenascin strongly labeled the sarcomatous tissue immediately around carcinomatous elements. Conclusions A similar immunoreactivity for p53 in both carcinomatous and sarcomatous components, expression of epithelial markers in the sarcomatous cells, and disruption of the basement membrane profile in areas of transition between carcinomatous and sarcomatous tissue, would all suggest, as has been postulated for extragenital sarcomatoid carcinomas, an origin from a common epithelial clone and an epithelial-to-mesenchymal transformation-based mechanism of development for this MMMT. In addition, these findings provide further analogies between these categories of tumors, supporting a unifying nosological concept for MMMTs and sarcomatoid carcinomas of non-genital tract origin.

Fine Aspiration versus Fine Cutting Needle, and Comparison between Smear Cytology, Inclusion Cytology and Microhistology in Abdominal Lesions

Two hundred patients underwent ultrasound guided percutaneous fine needle biopsy of focal solid abdominal lesions using 22 gauge aspiration and cutting needles. The material obtained by aspiration needle was treated by smear cytology and by inclusion cytology, and that obtained by cutting needle by microhistology. The retrieval rate was 89% for aspiration needle (smear cytology = 89%, inclusion cytology = 83.5%) and was 83% for cutting needle; the combined diagnostic accuracy was 98%. The typing accuracy was 76% for smear cytology, and was 84% for inclusion cytology and microhistology. We conclude that: 1. to obtain the highest retrieval rate (98%) both aspiration and cutting needles are necessary, because the aspiration needle is more likely to secure necrotic or soft tissue, and the cutting needle, fibrous or hard tissue; 2. histologic treatment of the samples yields a higher typing accuracy: 84% vs 76%; however, smear cytology remains essential because it permits a much faster evaluation of the adequacy of the sample and because it may avoid histologic methods in 76% of cases; 3. the smear cytology + microhistology combination seems to be the best solution (retrieval rate = 97.5%), but the costs are much higher because the cutting needle is somewhat expensive. The best solution would be to use the combination smear + inclusion cytology (retrieval rate = 89%) and to reserve the cutting needle for when aspiration needle material proves to be inadequate.

240 hepatocellular carcinomas: ultrasound features, tumor size, cytologic and histologic patterns, serum alpha-fetoprotein and HBs Ag.

Two hundred and forty cases of hepatocellular carcinomas (HCC), diagnosed by ultrasonography and fine needle biopsy, were studied. The following parameters were investigated: 1. echo features (240 cases) – hypoechoic, 54; hyperechoic, 56; complex, 112; isoechoic with halo, 18; 2. tumor size (240 cases) – single tumor under 4.5 cm, 30; single tumor over 4.5 cm, 74; multiple masses or diffuse, 136; 3. cytologic pattern (240 cases) – well and medium differentiated, 144; pleomorphic, 43; poorly differentiated, 28; unclassified, 25; 4. histologic pattern (157 cases) – trabecular, 74; solid, 42; acinar, 1; mixed, 2; unclassified, 38; 5. alpha-fetoprotein (AFP) level (185 cases) – under 20 ng/ml, 79; between 20 and 320 ng/ml, 40; over 320 ng/ml, 66; 6. HBs Ag (208 cases) – present in 56 cases; 7. cirrhosis (102 cases) –present in 79 cases. Some of the above parameters were correlated with one another. There was: 1. a highly significant frequency of the hypoechoic feature among small HCC; 2. a percentage of AFP-producing tumors increasing with tumor size; 3. no relationship between AFP production and cytologic or histologic pattern; 4. no relationship between tumor size and cytologic or histologic pattern. However, among the small HCC, all the 9 HCC with a diameter of less than 3 cm showed a trabecular pattern and well-differentiated cells. Cirrhosis was present in every patient with a small HCC. Since the discovery of a small HCC is an incidental ultrasonographic finding in the context of severe liver disease, ultrasonographic monitoring of cirrhotic patients is the best available strategy to screen for small HCC.

Hypocomplementemic Type II Membranoproliferative Glomerulonephritis in a Male Patient with Familial Lecithin-Cholesterol Acyltransferase Deficiency due to Two Different Allelic Mutations

Patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency very often show progressive glomerulosclerosis with evolution to end-stage disease. High levels of an abnormal lipoprotein (lipoprotein X) cause glomerular capillary endothelial damage. The ultrastructural study of renal biopsy specimens shows characteristic glomerular deposits of membrane-like, cross-striated structures and vacuole structures. The gene encoding for LCAT has been mapped to chromosome 16q22.1, and several mutations of this gene cause LCAT deficiency which is inherited as an autosomal recessive trait and which is characterized by corneal opacities, normochromic normocytic anemia, and renal dysfunction. Herein we report clinical features and renal histological findings concerning a 24-year-old male patient with classical familial LCAT deficiency due to two different allelic mutations: a nonsense mutation inherited from the father and a missense mutation inherited from the mother. Moreover, the patient showed glomerular histological lesions and an immunofluorescent glomerular pattern typical of hypocomplementemic membranoproliferative type II glomerulonephritis (dense-deposit disease). The nature of electron-dense material that characterizes dense-deposit disease is still unkwown, but there are suggestions that some chemical modifications might occur in the renal basement membranes. Therefore, this clinical case might induce to consider possible relations between disorders of the lipoprotein metabolism and renal dense-deposit disease.

Extracellular Matrix Globules in Renal Oncocytoma

Extracellular hyaline globules resulting from abnormal accumulation of matrix components have been described in several pathological conditions, including renal tumors. We studied 16 renal oncocytomas and observed these bodies in 11 of them. In these tumors, they showed a homogeneous texture as well as roundish, smooth contours, and were easily detected in hematoxylin-eosin sections in five cases. PAS staining greatly facilitated the identification of globules in the remaining six cases, where they were fewer in number. Immunohistochemically, they appeared to be composed primarily of basement membrane material, being strongly reactive to antibodies for type IV collagen, laminin, and heparan sulphate proteoglycan. In addition, a weak immunoreactivity for type I and type III collagen, and fibronectin was observed in some cases, whereas no globule stained for tenascin. We also analyzed 89 renal cell carcinomas, and found somewhat similar bodies in 10 of them. However, they were more scanty in the latter tumors, and displayed a more irregular configuration with granular or smudged contours. We conclude that, although the mere presence of extracellular hyaline globules does not justify a distinction between renal oncocytoma and renal cell carcinoma, the detection of a large number of well-demarcated, roundish extracellular bodies with smooth contours suggests renal oncocytoma.

Unusual morphologic features of a primary liver neoplasm.

Light and electron microscopy study of an unusual primary liver neoplasm observed in a 36-year-old woman. By light microscopy the tumor, initially detected by a needle biopsy and later surgically removed, was mainly composed of spindle-shaped and multinucleated cells which were similar to rhabdomyoblasts. These cells, however, showed ultrastructural features of hepatocytes.