Robert Fienberg

The protracted superficial phenomenon in pathergic (Wegener's) granulomatosis.

Twelve cases of pathergic (Wegeners) granulomatosis are described, with special attention focused on the long duration of mucosal and skin lesions in untreated cases, designated as the protracted superficial phenomenon, and on the histologic features that may be helpful in making the diagnosis. The long duration, often the result of a lack of proper interpretation of histologic details, was associated in some of the cases studied with the development of intractable renal failure or mutilation of the face. Since cytotoxic therapy offers the opportunity to prevent these complications, the desirability of an early diagnosis is obvious. Biopsy is the principal means of diagnosis, and therefore interpretation of histologic details is of paramount importance. Helpful histologic features found in the extravascular and vascular tissues of the specimens studed were focal necrosis, fibrinoid degeneration, palisading granulomas, giant cells, and vasculitis. Nonpalisading foci of granular necrosis or fibrinoid degeneration appeared to precede the development of the typical palisading granuloma. Both focal necrosis and focal fibrinoid degeneration occurred independently of intrinsic vascular involvement and in themselves are distinctive features of pathergic (Wegeners) granulomatosis. There was predominance of the extravascular components in the cases studied with occasional absence of vasculitis. Both the extravascular and vascular components are important in making a definitive diagnosis, but the extravascular component is characteristic, even in the absence of vasculitis. The extravascular tissues and the vessels are parallel contemporaneous target tissues.

The pulmonary biopsy in the early diagnosis of Wegener's (pathergic) granulomatosis: a study based on 35 open lung biopsies.

We reviewed open lung biopsies from 35 patients with Wegeners (pathergic) granulomatosis in order to study the histogenesis of the pulmonary lesions and to identify the early lesions. The process of pathergic necrosis is fundamental in the production of extravascular and vascular lesions and was divided into micronecrotic and macronecrotic types. Micronecrosis, usually with neutrophils (microabscesses), constitutes the early phase in the development of the pathognomonic organized palisading granuloma. The palisading granuloma differs from the compact granuloma of tuberculoid type, which occurs in infections and sarcoidosis but not in Wegeners (pathergic) granulomatosis. There is a progression of disease from micronecrosis to macronecrosis (widespread necrosis) and then to fibrosis. Macronecrosis surrounded by palisading histiocytes or diffuse granulomatous tissue indicates active disease, whereas necrosis surrounded by fibrous tissue indicates previously active disease. Most cases have a combination of micronecrosis, and fibrosis. We established the relative diagnostic value of various histologic features. Arteritis and phlebitis as classically described in Wegeners granulomatosis were present in most but not all cases. We believe that Wegeners granulomatosis primarily affects both vascular and extravascular collagen and reticulum and that vasculitis represents a primary necrosis of walls of blood vessels. We believe that the concept of Wegeners granulomatosis as a vasculitis is too restrictive and does not include many cases with only extravascular histologic changes.

Vasculitis in primary vasculitides, granulomatoses, and connective tissue diseases

Problems with the classification and diagnosis of vasculitides are discussed. The evidence related to the pathogenetic importance of immune complexes in vasculitis, both in experimental models and human disease, is reviewed. The finding, by immunofluorescence, of immunoglobulins and complement components in vessel walls has provided indirect evidence of a role of immune complexes in certain forms of human vasculitis. However, specific antigens have been demonstrated in very few instances, notably in some patients with hepatitis B infection. In most forms of human vasculitis there is no information about causative factors. The widely held belief that therapeutic drugs cause an appreciable proportion of cases of human vasculitis appears unfounded.

Correlation of antineutrophil cytoplasmic antibodies with the extrarenal histopathology of Wegener's (pathergic) granulomatosis and related forms of vasculitis.

We studied the histologic findings from extrarenal biopsies (especially of the lung or upper respiratory tract) or autopsies of 68 patients who were tested for serum antineutrophil cytoplasmic antibodies (ANCAs). We used antigen-specific assays to detect antibodies against proteinase 3 (PR3) and myeloperoxidase (MPO), the two types of ANCAs of proven diagnostic value for the spectrum of diseases that includes Wegeners (pathergic) granulomatosis, microscopic polyarteritis (microscopic polyangiitis), Churg-Strauss syndrome, idiopathic necrotizing and crescentic glomerulonephritis, and their variants. Twenty-eight patients had antibodies to PR3 and 16 had antibodies to MPO; no patient had antibodies to both. All 44 patients with ANCAs had histologic evidence of this spectrum of diseases. Thirteen patients without histologic evidence of this spectrum of diseases had negative tests for ANCAs. There were no pathologic features that reliably identified patients with one or the other type of ANCA. Eighteen of 31 patients with lesions of Wegeners granulomatosis had antibodies to PR3, seven had antibodies to MPO, and six had neither. Three of four patients with necrotizing arteries without granulomas had anti-MPO antibodies, but similar lesions were seen, together with extravascular granulomas, in three patients with anti-PR3 antibodies. Of 16 patients with alveolar hemorrhage, nine had anti-PR3 and five had anti-MPO antibodies. Two patients diagnosed clinically as having Churg-Strauss syndrome had anti-MPO antibodies. In 16 of the 25 patients with ANCAs and a histologic diagnosis of Wegeners granulomatosis the diagnosis was made on the basis of extravascular granulomatous lesions alone, which argues against the requirement for vasculitis. Of six patients with negative tests for ANCAs and histologically diagnosed Wegeners granulomatosis, none had evidence of renal involvement. We conclude that in the appropriate clinical setting the presence of anti-PR3 or anti-MPO antibodies provides reliable evidence of the above spectrum of diseases, but that subclassification (to the extent this is possible) depends on the presence of distinctive clinical or pathologic features. In patients with negative tests for ANCAs, interpretation of clinical and histologic findings remains the only definitive method of diagnosis.

A comparative histochemical study of the ovarian stromal lipid band, stromal theca cell, and normal ovarian follicular apparatus

I N A P R E v I 0 u s study of the stromal theta cell1 a peculiar accumulation of lipid was noted in the stromal spindle cells (the ovarian “fibroblasts”) forming a band just below the surface of the ovary. The distribution and location were different from those of the polygonal stromal theta cells, called luteinized stromal cells by Scully,” and there was no connection with the follicular apparatus. In the same study,l evidence was presented that a spindle form of the stromal theta cell was an early stage in the development of the polygonal form. Since the presence of lipid in the ovary appeared to be intimately connected with the synthesis of the steroid hormones, it was thought appropriate to compare the stromal spindle cells forming the lipid band with the stromal theta cells and the theta interna cells which are also derived from morphologically similar stromal spindle cells. Methods ap-

The stromal theca cell and postmenopausal endometrial adenocarcinoma

The ovaries found in 11 cases of postmenopausal endometrial adenocarcinoma were studied with the help of oxidative enzyme reactions and lipid, hematoxylineosin, and van Gieson stains. Stromal theca cells were found in the ovaries of 10 of the 11 cases with and without stromal hyperplasia and in one case, the ovaries contained small scars in a very cellular stroma representing involuted stromal theca cell groups. In the hematoxylin‐eosin stain, the stromal theca cells were obscured even in ovarian stromal hyperplasia, and the search for these cells was greatly facilitated by the utilization of a lipid stain and oxidative enzyme reactions. In view of the potential steroid hormone production of the stromal theca cell as indicated by the lipid and enzyme content and the high incidence of the cell in cases of postmenopausal endometrial carcinoma, it is concluded that attention should be directed to these cells and not to the previously reported ovarian stromal hyperplasia in studies of postmenopausal endometrial carcinoma.

Case 25-1989

Presentation of Case A 56-year-old man was admitted to the hospital because of hemoptysis. He was well until about three weeks earlier, when there was the onset of weakness, malaise, anorexia, and ...

Ovarian estrogenic tumors and diffuse estrogenic thecomatosis in postmenopausal colporrhagia: The importance of the benign endometrial mitosis

Abstract In 6 women of 60 years of age or over with vaginal bleeding, 2 cases of thecoma, 3 cases of mixed granulosa- and theca-cell tumor, and one case of estrogenic thecomatosis were found. Except for one woman with a postmenopausal period of amenorrhea of 2 years, the others had postmenopausal periods of 10 years or longer. No palpable adnexal masses were felt in 4 of these 6 women but all had hyperplasia of the endometrium with mitotic figures. The importance of mitotic figures as an indicator of estrogenic activity in the endometrium is stressed. It is recommended that any colporrhagic woman with a postmenopausal amenorrhea of more than 3 years and hyperplasia of the endometrium with mitotic figures should have an exploratory laparotomy whether or not a palpable adnexal mass is present, provided no estrogen has been administered. The use of the terms estrogenic thecomatosis and androgenic hyperthecosis is suggested to lessen the confusion due to morphologically similar cells producing different hormones.

Mucormycotic infection of arteriosclerotic thrombus of the abdominal aorta; report of a case.

THE importance of mucormycosis as a clinical entity is becoming more and more evident as indicated by the increasing number of cases in the literature. The case reported below is submitted because ...

The arias-stella reaction in early normal pregnancy—An involutional phenomenon: The ovary-placenta changeover as a possible cause*

Abstract In view of the apparent conflict between the recent finding of the Arias-Stella reaction in early pregnancy and our opinion of the regressive and involutional nature of this reaction based on a study of ectopic pregnancies and spontaneous abortions, we investigated 75 cases of therapeutic abortion in the first trimester. The Arias-Stella reaction was seen in 26, but features of degeneration were found in Arias-Stella reaction nuclei as well as focal decidual necrosis. Studies of hormonal levels obtained from the endocrinologic literature demonstrated declines during early pregnancy at the time of the ovary-placenta change-over. This association of the cytologic and histologic features of degeneration with declining hormone levels supports our opinion that the Arias-Stella reaction is a regressive phenomenon in early pregnancy as well as in ectopic pregnancy and spontaneous abortion.