Luciano Lombardi

Neuroendocrine (Merkel cell) carcinoma of the skin.

Merkel cell carcinoma was diagnosed in 10 patients (eight females and two males) with a mean age of 66 years and a range of 44–84. The most common sites of the primary tumor were the skin of the limbs, girdles, and head. Sixty percent of the cases had recurrences and 50% regional nodal metastases that appeared within 1 year. Of the patients treated variably with surgery, chemotherapy, and radiotherapy and followed for a mean period of 28 months, two were alive and free of disease, two were alive with disease after 3 and 6 years, and two have died of metastatic disease to the lungs and liver. The primary lesions showed quite distinctive clinical and gross features in terms of size, shape, and color. Histologically, the growth was usually diffuse and occasionally trabecular or pseudoglandular; infiltration was predominantly in the papillary and reticular dermis. The uniform, poorly cohesive cells contained argyrophilic granules in the cytoplasm and round to oval nuclei with frequently indented membranes. The mitotic index was high. Ultrastructurally, in two cases, two cell types were identified that probably represented the neoplastic counterpart of normal Merkel cells in different stages of maturation. Both cell types contained cytoplasmic neurosecretory granules and intermediate filaments, even though their cytoplasms were differently shaped.

Sclerosing angiomatoid nodular transformation (SANT): report of 25 cases of a distinctive benign splenic lesion.

Twenty-five cases of a morphologically distinctive vascular lesion of the spleen are described. The patients were 17 women and 8 men, ranging in age from 22 to 74 years (mean, 48.4 years; median, 56 years). The most common presentations were incidental finding of an asymptomatic splenic mass (13 patients), abdominal pain or discomfort (6 patients), and splenomegaly (4 patients). None of the patients had evidence of recurrent disease after splenectomy. The splenic lesion was solitary, measuring 3 to 17 cm, and sharply demarcated from the surrounding parenchyma. The cut surface revealed a mass of coalescing red–brown nodules embedded in a dense fibrous stroma. All cases showed a remarkably consistent multinodular appearance at low-power examination. The individual nodules had an angiomatoid appearance, in the sense that they were composed of slit-like, round or irregular-shaped vascular spaces lined by plump endothelial cells and interspersed by a population of spindly or ovoid cells. Some of the nodules (particularly the smaller ones) were surrounded by concentric rings of collagen fibers. Numerous red blood cells were present, as well as scattered inflammatory cells. Nuclear atypia was minimal, mitotic figures were extremely rare, and necrosis was consistently absent. The internodular stroma consisted of variably myxoid to dense fibrous tissue with scattered plump myofibroblasts, plasma cells, lymphocytes, and siderophages. Immunostaining revealed 3 distinct types of vessels in the angiomatoid nodules: CD34+/CD8−/CD31+ capillaries, CD34−/CD8+/CD31+ sinusoids, and CD34−/CD8−/CD31+ small veins, recapitulating the composition of the normal splenic red pulp. These features are therefore different from those of littoral cell angioma, conventional hemangioma, and hemangioendothelioma of the spleen. We interpret these angiomatoid nodules as altered red pulp tissue that had been entrapped by a nonneoplastic stromal proliferative process. The characteristic morphologic appearance, immunophenotype, and benign clinical course suggest that this is a distinctive nonneoplastic vascular lesion of the spleen that we propose to designate as sclerosing angiomatoid nodular transformation (SANT).

A Clinicopathologic Study of Primary Hepatic Carcinoid Tumors

Six cases of primary hepatic carcinoid tumors were studied with combined immunocytochemical and electron microscopic techniques. Positive tumor immunostaining with PHE5, LK2H10, neuron‐specific enolase (NSE), serotonin, gastrin, and insulin antibodies was observed. At the ultrastructural level, cytoplasmic dense granules were seen in all the cases tested. This finding supports a putative origin of these carcinoids found in the liver from a pluripotential stem cell. The clinical course and follow‐up of these cases suggests that this unusual hepatic neoplasm has a more favorable prognosis than other forms of hepatic cancer.

Electron microscopy analysis of early localization of cisplatin in ovarian carcinoma cells.

Taking advantage of the electron-dense nature of platinum, in this study the authors used an electron microscopy approach to investigate the cellular localization of cisplatin in an ovarian carcinoma cell line. Platinum spots were detected in contact with the plasma membrane and the nuclear envelope as well as in the cytoplasm and nuclear matrices. Contact with the plasma membrane was through a single blunt contact or spanning through the membrane. No sequestration in intracellular vescicles was observed, thereby supporting that phagocytosis and receptor-mediated endocytosis were not occurring. A molecular analysis indicated lack of expression of aquaporin 9, thus excluding its involvement in the membrane translocation of cisplatin. The present data suggest that cisplatin rapidly accumulates in the cell through endocytosis-independent membrane translocation and are consistent with passive diffusion.

Multienzymatic analyses of human malignant lymphomas. Correlation of enzymatic data with pathologic and ultrastructural findings in Burkitt's and lymphoblastic lymphomas

Enzyme activity measurements are of great relevance to the classification and biochemical characterization of the various types of leukemias, but they have been much less studied in solid lymphoid tumors. The authors report investigations in human lymphomas. The levels of the following enzymes were determined: terminal deoxynucleotidyl transferase (TdT), deoxyribonucleic acid polymerase alpha (DP alpha), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), thymidine and uridine kinases (TK and UK, respectively), and thymidine phosphorylase (ThPh). Moreover, cytochemical investigations were done in the group of Burkitts lymphoma (BL) and lymphoblastic lymphoma (LL), and ultrastructural studies were performed in seven of the nine LL of this series. These results were obtained: (1) TdT (90 cases) was highly specific for LL; eight of nine LL were positive, and all other histologic types were negative; the only TdT, acid esterase (AcE) positive, nonconvoluted LL was probably related to TdT normal medullary thymocytes, and had an unfavorable clinical course with resistance to a vincristine‐and‐prednisone‐including treatment; (2) ADA (61 cases) could distinguish clearly between the high levels of LL and the low levels found in any other group of lymphomas; among LL, the highest values were found in T‐cell‐derived neoplasias, and the lowest value in a periodic acid‐Schiff (PAS) positive, acid phosphatase negative case that showed the presence of large nucleoli at the ultrastructural analysis, a finding that is unusual for LL and possibly related to a more immature differentiation stage; (3) PNP (39 cases) values alone were not clinically relevant, but together with ADA levels, a subset of T‐LL with high ADA:PNP ratio could be selected among LL; (4) DP alpha (61 cases), and TK and UK (37 cases) were found in concentrations reflecting the malignancy of the non‐Hodgkins lymphoma, and were more elevated in the high‐grade malignant lymphomas; (5) ThPh (34 cases) was always elevated in Hodgkins disease, but low in Burkitts lymphoma and LL; thus, they had a high TK:ThPh ratio that could be useful in predicting clinical response to thymidine treatment. The authors think that taken together, multiple enzyme determinations could be useful in the characterization of human lymphomas.

Phagocytosis of Hemozoin (Native and Synthetic Malaria Pigment), and Plasmodium falciparum Intraerythrocyte-Stage Parasites by Human and Mouse Phagocytes

Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary,whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes functions.

Malignant histiocytosis: a histological and ultrastructural study of lymph nodes in six cases

A morphological, histological, and ultrastructural investigation was carried out on a series of six cases of malignant histiocytosis observed between 1973 and 1977. All lymph nodes were obtained prior to treatment. The histological findings revealed that the proliferating cell type was in all cases represented by histiocytes of varying degrees of atypia and with consistent phagocytic activity. In four cases, the histiocytic cellular proliferation also showed some degree of cohesiveness and, in two cases, there was capsular invasion. In three cases blood vessel invasion by malignant cells could be seen within the lymph node and in the surrounding tissue. On electron microscopy the tumour cells of malignant histiocytosis appeared to be pleomorphic with three types of cells: undifferentiated cells, histiocytes with variable degrees of differentiation, and cells with intermediate features. In particular, nonphagocytic and actively phagocytic histiocytes could be identified. The histological and ultrastructural data further support the idea that malignant histiocytosis is a disease that is related to the neoplastic proliferation of moderately differentiated histiocytes and their precursors. The latter may undergo various transformations with either apparently benign or definitely atypical morphological features.

Osteoclastoma-like giant-cell tumor of the liver. Case report.

The authors report a case of primary osteoclastoma-like giant-cell tumor of the liver and briefly discuss the histogenesis of this rare tumor.

Inflammatory pseudotumor of the liver: Report of two cases

Inflammatory pseudotumor of the liver is a very rare lesion. Herein we describe two cases of this entity which occurred in two women aged 22 and 49 years, respectively. Both cases were considered to be clinically malignant and only the histopathologic examination revealed the non-neoplastic nature of the disease. Ultrastructural and immunohistochemical studies further supported the evidence of a reactive disease.

A light microscopic and ultrastructural study of two cases of fibrolamellar hepatocellular carcinoma.

We describe two cases of fibrolamellar hepatocellular carcinoma of the liver in two young women. Both patients presented with diffuse intra-abdominal metastases; nevertheless they had a survival of 28 and 32 months, respectively, which sustains the better prognosis of this neoplasm. Electron microscopy of one case confirmed the oncocytic features of the neoplastic cells and showed intra- and intercellular duct-like vacuoles with numerous microvilli containing a microfilament core that terminated in a terminal web, which represents an unusual aspect in the spectrum of differentiation of fibrolamellar hepatocellular carcinoma.