Hector Battifora

Intra-abdominal desmoplastic small round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals.

Nineteen cases of a distinctive type of malignant smallcell tumor are presented. The main features of the entity are as follows: a predilection for adolescent males (mean age: 18.6 years); predominant or exclusive intraabdominal location, with only inconstant and secondary organ involvement: nesting pattern of growth; focal rhabdoid features; intense desmoplastic reaction; immunohistochemical reactivity for epithelial [keratin, epithelial membrane antigen (EMA)], neural [neuron-specific enolase (NSE)], and muscle (desmin) markers; and highly aggressive behavior. It is proposed that this represents yet another member of the continuously enlarging and evolving family of small round (blue) cell tumors of infancy and childhood that features, more than any other member of this group, the capacity for simultaneous multidirectional phenotypical expression.

Effect of formalin tissue fixation and processing on immunohistochemistry.

Although immunohistochemistry is routinely performed by many pathology laboratories, its standardization still lags behind. A major cause of variation in the reproducibility of immunohistochemical staining is induced by tissue fixation and, to a lesser degree, tissue processing. This report, stemming from the first meeting of the International Consensus Group on Standardization and Quality Control (ICGSQC) in Nice, France, summarizes the problem and suggests solutions to begin to achieve standardization of fixation and processing. Most laboratories use neutral-buffered formalin (10%) for tissue fixation which introduces cross-links, whereas coagulative fixatives are less popular. Problems with formalin fixation comprise delay of fixation and variations in the duration of the fixation mainly. Solutions to these problems could be to start fixation soon (<30 min) after surgical removal of the tissue and to avoid overfixation (>24-48 hrs). For tissue processing, the most important problem is inadequate tissue dehydration prior to paraffin embedding. This can be prevented by preparing all solutions freshly every week, depending on the volume of tissue processed. If consistently applied, these procedures could eliminate some of the sources of variation in immunohistochemical stains.

AMPLIFICATION OF c-erbB-2 ONCOGENE IN HUMAN ADENOCARCINOMAS IN VIVO

There are two genes related to the viral erbB gene in the human genome. c-erbB-1 is the same as the gene for the epithelial-growth-factor (EGF) receptor, and c-erbB-2 encodes a receptor-like protein very similar to, but distinct from, the EGF receptor. Hybridisation analysis of DNA from 101 fresh human malignant tumours showed that the c-erbB-2 gene was amplified in 5 of 63 adenocarcinomas and none of 38 other types of tumours, whereas the c-erbB-1/EGF-receptor gene was amplified only in 1 of 8 squamous-cell carcinomas. Thus, the protein products of the amplified c-erbB-2 gene may have a role in the evolution of adenocarcinomas, as does the EGF receptor in some squamous-cell carcinomas.

Further Evidence That Malignant Angioendotheliomatosis Is an Angiotropic Large-Cell Lymphoma

Malignant angioendotheliomatosis is a rare, generally fatal disease characterized by a multifocal proliferation of neoplastic mononuclear cells within the lumens of small blood vessels. Although the disease primarily involves the vasculature of the skin and central nervous system, vascular involvement of other organs may occur and may produce a variety of clinical findings. Some early investigators concluded that malignant angioendotheliomatosis was a neoplasm of endothelial cells, but recently others have suggested that it is of hematopoietic origin. We have studied three patients with the disease and have characterized the immunophenotype of the neoplasm on cryostat-cut fresh-frozen tissues. A detailed antigenic phenotyping of neoplastic lymphoid cells showed that one patient had the immunophenotype T11+, Leu-1+, Leu-3+, Leu-2+, B1-, B2-, SIg-, LN1-, LN2-, the predominant phenotype for peripheral T-cell lymphoma; the others had T11-, Leu-1-, Leu-3-, Leu-2-, B1+, B2+, SIg+, LN1+, LN2+, consistent with a B-cell-derived lymphoma. On the basis of our results, we suggest that angiotropic (intravascular) large-cell lymphoma would be more appropriate than malignant angioendotheliomatosis as a name for this disease.

Spindle cell carcinoma. Ultrastructural evidence of squamous origin and collagen production by the tumor cells

Two cases of spindle cell carcinoma (SCC) of the esophagus and skin, respectively, were studied by transmission electron microscopy. The tumor cells were closely associated with collagen fibrils and had abundant rough endoplasmic reticulum with dilated cisternae. Except for their irregular shape and atypical nuclei they resembled actively synthesizing fibroblasts. In addition to these features, some cells contained numerous tonofibrils and occasional well‐developed desmosomes. A gradual transition to typical squamous cells was noted in the skin tumor. These findings suggest that the pseudosarcomatous component of SCC originates from mesenchymal metaplasia of squamous cells and that collagen is produced by these metaplastic cells.

Malignant fibrous histiocytoma. An electron microscopic study.

Sixteen cases of malignant fibrous histiocytoma are presented. Electron microscopy of 15 cases demonstrated fibroblast‐like and mononuclear and multinucleated histiocyte‐like cells. A small capillary was at the center of all storiform areas exmained. Ultrastructural examination can be diagnostically useful within the context of a narrow differential diagnosis by conventional microscopy and the ability, by electron microscopy, to eliminate other mesenchymal cell types. In 13 cases, follow‐up information was available from 18 months to 9 years following histological diagnosis. Five patients are alive and 8 patients have died, including two non‐tumor related deaths. In 3 cases follow‐up was less than 4 months. The biologic behavior of the tumor in this series was generally not related to histopathological parameters. The issue of histogenesis is largely unresolvable. Ultrastructural studies of various types of fibrous histiocytomas, suggesting cells of origin other than histiocytes, give credence to the concept that the histiocyte may represent a morphologic state of a given mesenchymal cell rather than a particular cell type. Cancer 40:254–267, 1977.

Hemangiopericytoma: ultrastructural study of five cases.

Five soft tissue hemangiopericytomas exhibiting the range of histologic types common to this tumor were studied with the electron microscope. Morphological correlates revealed that the better differentiated pericytes were present in the tumors or areas thereof displaying open capillaries, scant connective tissue, and oval, plump tumor cells. These findings support the concept of a pericytic histogenesis of this neoplasm. Well‐differentiated pericytes were harder to find in areas with perivascular fibrosis and in tumors featuring spindle‐shaped pericytes. Apparent forms of transition between pericytes and endothelial cells were common, especially in the less well‐differentiated tumors. In one of these, atypical endothelial cells resembling those of endothelial sarcomas were present. These findings are suggestive of a close histogenetic relationship between hemangiopericytoma and hemangioendothelioma.

Interpretation and quantification of immunostains

Despite the fact that immunohistochemistry is widely used in routine diagnostic work and is a very common part of scientific reports in pathology and cytology, its standardization still lags behind. Interpretation of immunostains should be based on microanatomic distribution of the staining, proportion of positively stained cells, staining intensity, if relevant, and cutoff levels. These parameters should be shown to be reasonably reproducible and should be clearly defined in publications. Uniformity in the setting of thresholds could probably benefit from interlaboratory control materials containing defined amounts of the target antigen. Reliable and precise quantitative immunohistochemistry requires the use of control materials containing defined amounts of the target antigen and processed alongside the specimen combined with automated computer-assisted microspectrophotometry. Application of these suggestions is hoped to improve standardization and to facilitate communication in the field of immunohistochemistry.

Angiotropic (intravascular) large cell lymphoma. A clinicopathologic study of seven cases with unique clinical presentations.

The authors recently reported the antigenic phenotypes of three cases of so‐called “malignant angioendotheliomatosis” and suggested that angiotropic large cell lymphoma (ALCL) is a more appropriate designation for this disease. The authors now report an additional seven cases of ALCL with unique clinical presentations. One patient presented with prostate enlargement, the second with lytic bone lesions and thickened nasal sinus mucosa, the third had diffuse myalgia, the fourth had dyspnea and pulmonary infiltrates, the fifth had gangrene of the lower extremities, total‐body skin involvement, and pancytopenia, the sixth had a lesion of the foreskin mimicking squamous cell carcinoma, and the seventh had a mediastinal mass. In all cases histologic features were characteristic of ALCL with, in two cases, extravascular spread into soft tissue. Immunohistologic studies showed a B‐cell phenotype in five cases and a T‐cell phenotype in one case. Two patients received combination chemotherapy using established treatment protocol for large cell lymphoma, and remain in complete clinical remission and two patients are responding clinically to combination chemotherapy. Two patients died shortly after receiving combination chemotherapy. One patient has only recently been diagnosed as having ALCL and no long‐term follow‐up is available. These data indicate that, although ALCL affects predominantly the central nervous system and skin, unusual clinical presentations may occur, and patients with ALCL may respond to combination chemotherapy for large cell lymphoma.

Leu-M1 antigen in human neoplasms. An immunohistologic study of 400 cases.

Several studies have shown that the Leu-Ml antigen, a monocyte/granulocyte-related marker, is consistently expressed by the neoplastic cells of patients with Hodgkins disease (HD). It has been suggested that reactivity of Reed-Sternberg cells with Leu-Ml can be used in support of a morphologic interpretation of HD, and that it is helpful in the differential diagnosis of HD from morphologically similar lesions. To evaluate the significance of the Leu-Ml positivity of Reed-Sternberg cells in the diagnosis of HD, we investigated the distribution of Leu-Ml antigen in a series of patients with HD, non- Hodgkins lymphomas, and nonhematopoietic neoplasms. We were able to demonstrate the presence of Leu-Ml antigen not only in the majority of patients with HD, but also in 12 of 18 (67%) peripheral T-cell lymphomas, as well as in a variety of nonhematopoietic neoplasms, which included 113 of 199 carcinomas, most of them (58%) adenocarcinomas. Only one of 34 sarcomas showed a focal positive reaction. Leu-Ml-related antigen was not detected in any of 18 mesotheliomas, 15 germ cell tumors, 13 melanomas, three schwannomas, or three astrocytomas. Our study indicates that Leu-Ml positivity has no value in supporting the diagnosis of HD in situations where the histologic diagnosis of HD is doubtful. However, since anti-Leu-Ml reacted positively in the majority of adenocarcinomas but was absent in mesotheliomas, melanomas, and most sarcomas, this antigen could serve as a new marker that may be helpful in situations in which carcinoma is a part of the differential diagnosis.