CONTRIBUTION TO THE HISTOPATHOLOGY OF FILARIASIS

Transcription

1 CONTRIBUTION TO THE HISTOPATHOLOGY OF FILARIASIS PHILIP H. HARTZ Public Health Service, Curacao, N.W.I. The histologic changes caused by filariasis (Wucheria Bancrofti) are considered to be non-specific and not typical and accordingly very little can be found concerning this subject in the textbooks of parasitology and tropical medicine FIG. 1. ATYPICAL GIANT CELL AND EPITHELOID CELLS IN A LYMPHNODE. X 1500 Pasternack 5 reported recently two cases in which biopsy revealed unsuspected filarial disease and one of which showed an epitheloid cell granulomatous endolymphangitis. Unfortunately his photomicrographs do not show much histological detail, except that the filaria depicted in his fig. 2A must also be considered as dead. The epitheloid cell granulomatous endolymphangitis, especially when combined with epitheloid cell perilymphangitis and eventually with changes in the lymphnodes, must, in our opinion be considered as fairly typical of filariasis, as we found it in 5 out of 10 cases. In several of our cases the presence of the 34

2 HISTOPATHOLOGY OF FILARIASIS 35 typical histologic lesions was the reason for the examination of several more blocks of tissue, which lead to the finding of the filaria. In view of the expected increase of the incidence of filariasis and the difficulties which sometimes are encountered in the histologic diagnosis, especially when the localisation of the lesions is atypical, a detailed description does not seem superfluous. REPORT OF CASES Case 1. A white girl, 10 years old, native of Curacao, was operated upon because of a small tumor between the right breast and the axilla. Two weeks prior to operation the FIG. 2. EPITHELOID CELLS IN A LYMPHSINUS. X 1500 tumor had been tender and the skin over it red and swollen. Histologic examination proved the tumor to be a lymphnode. The most striking change consisted in the presence of small accumulations of epitheloid cells throughout the node. They where found not only in the intermediate sinuses but also in the cortical follicles and there even in the germ centers. The cells had oval to bandlike nuclei with a sharp nuclear membrane and a small but distinct nucleolus. The protoplasm stained pale, so that the groups of epitheloid cells could easily be found in the dark staining lymphoid tissue. Sometimes there were Langhans giant cells between the epitheloid cells and in one section an isolated giant cell of the Langhans type was lying in a germ center (fig. 1). In the sinuses and efferent and afferent lymphatics epitheloid cell granulomatous lymphangitis was observed (fig. 2). In

3 36 PHILIP H. HARTZ an efferent lymphatic an adult, well preserved macrofilaria was found, which in one place had indented the wall of the vessel. In the periglandular connective tissue the remnants of a dead macrofilaria were encountered; they were surrounded by a narrow, inner necrotic zone and an outer zone consisting of epitheloid cells, between which there were thin fibers, staining blue with the azan-stain. There were also several giant cells of the Langhans type. In the neighbouring connective tissue several pseudo-tubercles were found. There were only a few eosinophilic leukocytes and no caseation or acid-fast bacilli. FIG. 3. EPITHELOID CELL. GRANULOMATOUS PERI- AND ENDOLYMPHANGITIS IN THE FUNICULUS Part of the muscular coat of the vessel is visible. X 350 Case 2. A white man, 43 years old and native of Curacao, was hospitalized because of a slowly growing hydrocele. A diagnosis of tuberculous epididymitis was made and semicastration performed. Sections of the thickened cord, which were examined first, showed epitheloid cell granulomatous endolymphangitis. The walls of the lymph vessels were densely infiltrated by lymphocytes and small groups of epitheloid cells (figs. 3, 4). No caseation was found, however, and the vas deferens showed no pathologic changes. Sections of the epididymis proved that the efferent ductules and the ductus epididymidis also were everywhere intact. The connective tissue between the ductules was edematous and in many places densely infiltrated with lymphocytes. Everywhere epitheloid cell granulomatous peri- and endolymphangitis, together with dilatation of many lymphatics were observed. In several

4 HISTOPATHOLOGY OF FILARIASIS 37 vessels Langhans giant cells were found, also pseudo-tubercles in the neighbourhood of lymphatics. Eosinophilic leukocytes were absent. In one lymphvessel an intact macrofilaria was found. It was partly surrounded by lymphocytes, monocytes and a few epitheloid cells. The endothelium of the lymphvessel was intact. The filaria was in all probability alive at the moment of fixation, as a mitotic division was found in its intestinal epithelium. t Case 3. A colored girl, six years old, was hospitalized because of slowly developing enlargement of the left inguinal lymphnodes. Bloodcounts showed nothing abnormal and thick bloodsmears no microfilaria. A lymphnode was removed for microscopical examination. FIG. 4. SAME AS PIG. 3. X 700 The lymphnodes showed well developed follicles with germ centers. The sinuses were wide and very conspicuous. Very little remained of the reticulum of the sinuses; in its place groups of lymphocytes, macrophages and epitheloid cells were found. Sometimes there were giant cells of the Langhans type, either isolated or accompanied by epitheloid cells. Especially in the lymphatics of the hilar region typical epitheloid cell granulomatous endolymphangitis was found; here also Langhans giant cells or atypical giant cells were encountered. In the connective tissue there were several pseudotubercles and infiltrates composed of plasma cells. A few eosinophilic leukocytes were found in the lymphnode and none in the periglandular connective tissue. As the histological lesions were considered

5 38 PHILIP H. HARTZ typical for filariasis, serial sections were made and a pregnant female macrofilaria was found. The tissues of the worm and the embryos showed many mitotic divisions, which fact makes it almost certain that the worm was living at the moment of fixation. GENERAL DESCRIPTION OF THE LESIONS From the case reports can already be concluded that the lesions, which, apart from the dilatation of the lymphatics, we consider as typical for the presence of macrofilaria, can be found in the lumen and the wall of the lymphatics, in the FIG. 5. ACCUMULATION OF EPITHELOID CELLS AND LYMPHOCYTES IN THE LUMEN OF A LYMPH VESSEL. X 700 lymphnodes and in the connective tissue. As the changes of the lymphatics are the most conspicuous and, in our opinion, the most typical, they will be described first. The epitheloid cell granulomatous endolymphangitis can present different aspects probably according to the age of the lesion. In its most simple form it presents itself as a more or less loose collection of epitheloid cells, histiocytes and lymphocytes, in general without connection with the wall of the vessel, which has

6 HISTOPATHOLOGY OF FILARIASIS 39 an intact endothelium (figs. 5 and 6). In this stage there is generally no regular arrangement of the different cell types. Transitional forms between histiocytes and epitheloid cells can easily be found; mitotic divisions are also present; once a multipolar division was seen. The form of the epitheloid cells does not differ from that of the epitheloid cells found in tuberculosis. The nuclei are oval or more elongated, often bandlike or slightly curved, have a sharp nuclear membrane and usually one small but conspicuous nucleolus. PIG. 6. SAME AS PIG. 5. NOTE MITOSIS. X 1500 In what is perhaps a more advanced stage, the epitheloid cells are lying more closely together, the cell borders are often indistinct, and only a few lymphocytes are seen between them, though these cells may be present in greater numbers around the accumulations of epitheloid cells. Sometimes slender threads of fibrin are seen between the epitheloid cells; when the filaria were intact, we never observed necrosis. The smaller lymphatics become obliterated by this process as their lumen becomes nearly filled by the granulomatous mass (fig. 8). In this stage mitotic divisions are still observed in the epitheloid cells. Thin connective tissue fibers,

7 40 PHILIP H. HARTZ which stain blue with the azan stain, appear between the cells. We believe that this process will ultimately lead to fibrosis. The endothelium remains intact until the vessel is obliterated. In the larger and wider vessels the accumulations of cells are often found in the direct neighborhood of or in direct contact with the valves, which can also show an important thickening, caused by cellular infiltration. Though the cellular masses do not completely fill the lumen and remain FIG. 7. ACCUMULATION OF EPITHELOID CELLS AND LYMPHOCYTES IN THE LUMEN OF A LYMPH VESSEL, COVERED BY ENDOTHELIUM AND APPARENTLY WITHOUT CONNECTION WITH THE WALL OF THE VESSEL. X 350 floating in the lymph, development of connective tissue fibers can also be observed here. This development of granulation tissue from cells which originally were lying free in the lumen of the vessels is combined with another process: the narrowing and obliteration of the lymphatics by granulomatous perilymphangitis. The product of this perilymphangitis resembles very much small epitheloid cell tubercles, with or without giant cells. In general it leads to a narrowing of the lymph vessels, whose endothelium is pushed towards the lumen. Sometimes rounded

8 HISTOPATHOLOGY OF FILARIASIS 41 apparently' isolated granulomatous masses are found in the lumen of the vessels; in contrast to the granulomas developed in the lumen of the vessels, they are covered with endothelium (fig. 7). On serial sections they are seen to be connected with the wall of the vessels (fig. 9). This microscopical picture is, in our opinion, also typical for filariasis. In the lymphnodes the changes consist of the occurrence in the sinuses of small groups of epitheloid cells (fig. 2), sometimes combined with Langhans giant cells or more atypical giant cells (fig. 1). They can also occur in the lymphatic tissue. FIG. 8. SMALL LYMPHVESSEL, COMPLETELY OBLITERATED BY GRANULOMATOUS MASS One mitosis in the field. X 700 Isolated giant cells are also observed. There is often pronounced dilatation of the sinuses. We believe that here the epitheloid cells develop from the reticulum cells. In the connective tissue small pseudo-tubercles and infiltrates, composed of plasma cells and lymphocytes are found. In those cases, where the filaria were fixed when still living, eosinophilic leukocytes were either absent or present only in very small numbers. When the filaria had died some time before the operation sometimes very great numbers of eosinophiles could be found. In one case, where a biopsy from the red and swollen epididymis was taken, necrotic j

9 42 PHILIP H. HAKTZ filaria and enormous masses of eosinophilic leukocytes were encountered. Though clinically and on gross examination an acute inflammation was diagnosed, neutrophilic leukocytes were absent. If this inflammation had been caused by streptococci or staphylococci another composition of the cellular infiltrate should be expected. Dead macrofilaria are often surrounded by a zone of necrosis, which is walled of by epitheloid cells and giant cells. This can be mistaken for tuberculosis, especially when pseudo-tubercles are found in the neighborhood and the body of FIG. 9. GRANULOMATOUS MASS IN THE LUMEN OF A LYMPHVESSEL, COVERED WITH ENDOTHELIUM. X 700 the filaria has disintegrated. In such cases the presence of the endo- and perilymphangitis, which as in Pasternack's case 2, can be present a certain time after the death of the worm, can lead to the right track, and when many sections are examined, rests of the cuticula of the worm can usually be found and the diagnoses of filarial disease be made. SUMMARY In 5 out of 10 cases of filariosis epitheloid cell endo- and perilymphangitis was found, sometimes combined with analogous changes in the lymphnodes. These

10 HISTOPATHOLOGY OF FILARIASIS 43 processes seem to be caused by the presence of living macrofilaria, though they can still be present some time after the death of the worms. The changes must be considered as typical, but not as specific for filariasis and form a strong indication for the search of the worm. They should not be mistaken for tuberculosis. REFERENCES (1) BKUMPT, E.: Precis de Parasitologic. (4) STRONG, RICHARD P. Stitt's Diagnosis, Paris, Masson et Cie, Prevention and Treatment of Tropical (2) FAUST, ERNEST CARROL: Human Hclminthlogy. Philadelphia, Lea and Diseases. Philadelphia, The Blakiston Company, Febiger, (3) MANSON-BAHR, PHILLIP H.: Manson's (5) PASTERNACK, JOSEPH G.: Filarial epididymofuniculitis. Arch. Path., 35: Tropical Diseases. London, Cassel and Company Ltd., , 1943.