Centrofacial malignant granulomas. Clinicopathologic study of 40 cases and review of the literature.

An important problem in the treatment of centrofacial ulcerations is to establish a precise diagnosis, since similar clinical and microscopic findings can result from many different causes (as in the centrofacial malignant granuloma syndrome [CFMG]). A comprehensive surgical biopsy protocol (known as SNFMI/GMCF), involving microbiology, parasitology, immunology and pathology laboratories, allowed us to evaluate and to treat 40 cases of CFMG, who form the basis of this report. In 13 of them, specific diagnoses were found and curative treatments could be given. In the remaining 27, the optical microscopy pattern met the criteria for CFMG without identifiable origin or the presence of so-called lethal midline granulomas; however, a more precise evaluation with the help of immunofluorescence studies led to the recognition of malignant lymphoma (ulcerative lymphoma of the midface [ULM]). Most of these lymphomas belonged to the T cell lineage; the others were of B lymphoid origin, or, more rarely, of histiocytic origin. Patients with ULM received radiotherapy and chemotherapy with a response rate of 70.3%; however, the toxicity was significant, with frequent occurrence of chemotherapy-induced neutropenia followed by severe infectious facial cellulitis. Six patients were enrolled in a preliminary open trial of treatment with recombinant alpha-2b interferon with little success. Three patients were treated with radiation therapy only, and survived. Thus, CFMG is a syndrome with specific causes and treatments, requiring multiple extensive biopsies to make the correct diagnosis. The recognition of ULM as the cause of the previously called "lethal midline granulomas" leads logically to the use of chemotherapy with growth factors in order to ameliorate its bad prognosis.

Systemic polyarteritis nodosa diagnosed at hysterectomy.

A 61-year-woman was referred because of declining general health. A diagnosis of uterine malignancy was suspected on the basis of uterine enlargement and an elevated erythrocyte sedimentation rate. Hysterectomy was performed, and histologic examination revealed necrotizing vasculitis affecting the ovaries, fallopian tube, and uterus. Muscle biopsy showed typical periarteritis nodosa lesions. Despite the scarcity of such cases, the incidental finding of necrotizing arteritis in a surgical uterine specimen warrants further investigation to determine if the vasculitic process is localized.

Proteoglycans detected by monoclonal antibodies in adenoid cystic carcinoma of salivary glands.

Thirty-two cases of adenoid cystic carcinoma (ACC) of the salivary glands were examined immunohistochemically by monoclonal antibodies to proteoglycans (PG) such as chondroitin 6 sulfate (C6SPG), chondrotin 4 sulfate (C4SPG), dermatan sulfate (DSPG), heparan sulfate (HSPG) and keratan sulfate (KSPG) in conjunction with specific enzymatic digestion. The cribriform structure of ACC consisted of basaloid, myoepithelium-derived, and luminal tumor cells. The myoepithelial tumor cells were positive for PG, whereas luminal tumor cells were unstained. Occasional pseudocysts also gave positive staining for PG. Tubular structures consisting of modified myoepithelial cells indicated a high intensity reaction for C6SPG and C4SPG, and a slight one for DSPG, HSPG, and KSPG. Immunodepositions in solid and cluster structures were comparatively light in terms of PG. Basement membrane in ACC stained strongly for C4SPG, slightly for C6SPG, and very slightly for DSPG, HSPG, and KSPG. In ACC, immunohistochemical staining of PG was regularly positive in myoepithelium-derived tumor cells, but was irregular in other types of tumor cells.

[Lethal midline granuloma of unknown cause: 6 new cases and review of the literature]. / Granulome malin centro-facial de cause inconnue: six nouvelles observations et revue de la littérature.

The term of "lethal midline granuloma" has been used to apply to a number of diseases. In this paper, it is argued that this term should be only a clinical description of a relentlessly progressive destructive lesion of the nose and face. A list of all the possible causes is presented. There is a group of patients who do not correspond to any specific etiology. Reviewing the observations in the literature and our own, we think that such cases are best classified according to their histological appearance. Those without atypical cells (20% of cases) are always localized to the upper respiratory tract, while those with atypical cells (histiocytes?), 80% of cases, may become generalized and/or may evolve to a malignant lymphoma. When localized, both forms (with and without atypical cells) respond very well to high-dose radiation therapy (40 to 60 Gy). In disseminated forms or relapses following radiotherapy treatment, chemotherapy, the only available alternative treatment, has met with little success. We present the clinical and pathological features of six such patients, of whom one had no atypical cells. Radiotherapy produced a clinical remission in five of five cases, but of shorter duration than that reported in the literature. No treatment other than radiotherapy has yet proven to be regularly efficient in this rare and mutilating disease.

Origin of malignant centrofacial granulomas: surface markers and gene rearrangement of malignant cells.

Malignant centrofacial granuloma (MCFG) is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, palate, and face, without any demonstrable etiology. The origin of 11 cases were analyzed with the help of cell-surface immunostaining in all and with T-cell receptor gene (TCR) rearrangement in 3. The results show that most of the cases of MCFG are in fact T-cell lymphomas with cell-surface antigens (CD2, CD7, CD3) consistent with either early or mature T lymphocytes. However, some cases exhibit B-lymphoid (CD19, CD20) or histiomonocytic (CD13, CD14) lineage-specific markers. In conclusion, despite its remarkable clinical unity, MCFG is a heterogeneous group of neoplastic diseases, most but not all of which may be classified as T-cell lymphoma.

Hemolytic uremic syndrome in patients with Behçet's disease treated with cyclosporin A: report of 2 cases.

Hemolytic uremic syndrome (HUS) has been reported in patients treated with cyclosporin A (CsA) following bone, hepatic and kidney transplantation. We report two patients with Behçet's disease (BD) under CsA treatment because of severe uveitis, who developed HUS several months after the initiation of treatment. Renal biopsies showed lesions consistent with the diagnosis of the arterial form of thrombotic microangiopathy: vascular thrombosis with extensive glomerular ischemia. Renal failure persisted after withdrawal of CsA: one patient is in chronic renal failure (CRF) with a 4-year follow-up; the other died after refusal of chronic hemodialysis. In our two patients, excessive doses of CsA with high trough levels are likely to have contributed to the development of HUS. A rapid adjustment of CsA doses and an early detection of signs of the microangiopathic process might have prevented this severe complication of CsA treatment.

Ameloblastic fibrosarcoma of the jaws--report of three cases. Clinico-pathologic, histoenzymological and ultrastructural study.

The ameloblastic fibrosarcoma is a rare variety of neoplasm. Three new cases reported here occurred within preexistent benign odontogenic tumors (ameloblastic fibroma or fibro-odontoma). These large, osteolytic tumors, spreading to adjacent soft parts, recurred after surgical treatment in two cases. One of them had a lethal course, with pleuro-pulmonary, mediastinal lymph node and hepatic metastases. Histologically, these sarcomas show a malignant mesenchymal component and few benign ameloblastic islands, which often disappear after one or several recurrences. Histoenzymologically, a high level of alkaline phosphatase and ATPase activities is always present, a feature not present in common fibrosarcomas. The ultrastructural study demonstrates, in analogy with odontogenic myxomas, clear cells provided with numerous microfilaments, secretory cells and also some fibroblasts and myofibroblast-like cells. In addition to these pleomorphic cells, a great number of peculiar granular cells with numerous lysosomal bodies were also found. The histogenesis of these tumors in unknown. Perhaps the epithelial component, being unable to assume its functions of organization, may initiate the malignant transformation of its odontogenic mesenchyme.

Stromal changes in early invasive breast carcinoma. An immunohistochemical, histoenzymological and ultrastructural study.

The purpose of this work was to detect in periductal connective tissue of breast carcinoma in situ changes induced by intraductal tumor cells before any dehiscence in basement membrane. Histological, electron microscopic, immunohistochemical and histoenzymological methods were used in 3 carcinomas in situ, 4 microinvasive carcinomas and 13 control invasive carcinomas. We could demonstrate a high functional activity of fibroblasts with secretion of mucopolysaccharides and type III collagen around intraductal carcinomas. These changes occurred simultaneously to those of the basement membrane which was either thinning or thickening. Any dehiscence in basement membrane secondarily induced in this periductal stroma the usual changes seen in invasive stroma, peculiarly numerous vascular pedicles, myofibroblasts, elastic material. These periductal stromal changes are interpreted according to recent concepts about the possible influence of tumor cells upon their environment: stimulation of mitotic and metabolic activity of fibroblasts: stimulation of angiogenesis by means of an angiogenic factor.

Effects of estradiol and promegestone on human breast cell cultures. An ultrastructural study.

Effects of estradiol (E2) and promegestone (R 5020) were tested on primary cultures of epithelial human breast cells prepared from surgical specimens of reduction mammoplasty. Comparative morphological studies were performed by means of transmission and scanning electron microscopy in cells without any hormonal adjunction and in those previously treated with E2 or E2 + R 5020. The results were as follows: In basal medium used as control the majority of epithelial cells, although well-differentiated, remained flat with few microvilli, well-developed Golgi apparatus and rough endoplasmic reticulum, was obvious. R 5020 added with E2 increased differentiation of epithelial cells covered with scarce long and branched microvilli, but reduced the turn-over of young cells. E2 seemed to generate more active proliferation of cells. R 5020 inhibited this effect and induced a higher differentiation of mammary epithelial cells.

An immunohistochemical study of the distribution of lysozyme, lactoferrin, alpha 1-antitrypsin and alpha 1-antichymotrypsin in salivary adenoid cystic carcinoma.

The immunohistochemical expression of lysozyme (Ly), lactoferrin (La), alpha 1-antitrypsin (alpha 1-AT), and alpha 1-antichymotrypsin (alpha 1-Ach) was described, and their distributions were compared to each other in 28 cases of adenoid cystic carcinoma (ACC) of the salivary glands. ACC materials were obtained from the parotid gland (7), the submandibular gland (4), the sublingual gland (8), and minor oral salivary glands (9). Histopathologically, ACC was classified into cribriform (14), tubular (3), and basaloid or solid patterns (11). Positive staining for Ly was found in 1 case of solid ACC in the sublingual gland; La was found in 4 cases (2 cribriform, 1 tubular, 1 basaloid) in the sublinguals (3) and parotid glands (1); alpha 1-AT was found in 6 cases and alpha 1-Ach in 17 cases. The immunohistochemical localization of Ly and La was usually confined to luminal tumor cells of tubulo-ductal structures, irrespective of the pathologic types. Positive staining for alpha 1-AT and alpha 1-Ach appeared in tumor cells of cribriform, tubular and solid ACC. Tumor cells with positive La staining coincided with a positive reaction to alpha 1-AT and alpha 1-Ach, and tumor cells with alpha 1-AT positive deposition were also positive for alpha 1-Ach. The contents of pseudocysts in the cribriform pattern showed a positive reaction to La, alpha 1-AT, and alpha 1-Ach. Of the 28 cases of ACC, positive expressions for Ly, La, alpha 1-AT and alpha 1-Ach were found with a high frequency of alpha 1-Ach staining (17 in 28 cases were positive). In sublingual ACC (8), 7 cases were positive for immunohistochemical reactions. Co-expression or simultaneous expression for Ly, La, alpha 1-AT, and alpha 1-Ach in ACC suggest that tumor cells are protected from proteolysis or degradation.

Scanning electron microscopy of normal, malignant and post radiotherapeutic oral mucosal cells.

A scanning electron microscopic study of 40 oral mucosal smears from healthy controls or patients with cancer of the mouth has enabled a comparison of the "external" characteristics of normal, malignant and dysplastic (post-radiotherapeutic) cells. Normal cells, particularly the cells of the superficial epithelial layers, were characterized by well-defined polarized external protrusions with ridges on the upper surface and microvilli on the under surface. In cancer cells, both the shape and arrangement of these formations were profoundly altered. Dysplastic cells presented an intermediate appearance which was sufficiently characteristic to allow them to be distinguished from neoplastic cells.

Behcet's syndrome and renal involvement: a histological and immunofluorescent study of eleven renal biopsies.

The finding of focal glomerulonephritis in a patient with Behcet's syndrome led us to perform systematic renal biopsies in ten other patients with the disease. None of the patients had symptoms of renal disease. Proteinuria was found in five, two of whom had associated leukocyturia. By light microscopy mesangial and extramembranous glomerular deposits were observed in eight patients. Arterioles in ten patients showed subendothelial and medial hyaline deposits. A granular pattern of fluorescent staining identified the presence of the third component of complement in these deposits. Circulating immune deposits were sought and found in six out of seven patients. The finding of circulating immune complexes and deposition of complement in glomerular and arteriolar tissues supports an immune complex mediated nephropathy and is consistent with the hypothesis of an immunological pathogenesis in Behcet's syndrome.

Cherubism. Histo-enzymological and ultrastructural study.

The 3 cases of cherubism reported affected the mandible. They were all studied by means of histo-enzymological and ultrastructural methods. This study demonstrated 3 stages in the morphological evolution of the disease, corroborated by clinical data. The 1st stage was characterized by an osteolytic granuloma with round, fusiform and giant-cells and a high level of activity of acid phosphatase. The 2nd stage showed repair with proliferation of highly active fibroblasts (increase in activity of leucine aminopeptidase). The 3rd stage exhibited an osteogenesis with high activity of alkaline phosphatase and ATPase. The pathogenesis of this rare osteodysplasia is discussed.

Scanning electron microscopy in oral cytology.

Sixty-three cell smears from oral mucosa were studied by scanning electron microscopy. Among them, smears from ten healthy controls showed three kinds of cells: flat (superficial) cells with linear anastomosing microridges and microvilli; polygonal (intermediate) cells with well-defined crests between their faces and numerous microvilli; and round (parabasal) cells entirely covered by microvilli. Twenty-five smears from patients with untreated squamous-cell carcinoma showed enlarged polymorphous cells (round, globular, and elongated); microvilli, variable in their dimensions, were irregularly distributed on their surfaces. Eighteen smears from patients with severe epithelial dysplasia showed polymorphous cells with discontinuous but obvious edges separating their faces and with irregular microvilli and ridges. Nine smears were also performed in patients with various other mucosal lesions (lichen planus, leukoplakia, white sponge naevus, pemphigus vulgaris, and herpes). All of these smears were studied comparatively between examination of smears and biopsies by light microscopy. The smears were truly reliable, particularly for distinguishing between dysplastic and tumoral cells.

[Small cell carcinoma. Incidence, histopathology and anatomical features. Analysis of 465 autopsied bronchopulmonary carcinomas (author's transl)]. / Le cancer bronchique à petites cllules: fréquence, histopathologie et évolution anatomique; analyse d'un recrutement nécropsique de 465 cancers bronchopulmonaires.

465 patients with broncho-pulmonary malignant tumors have been autopsied. Small cell carcinoma was diagnosed in 22.5 per cent of these patients. The histo-cytological variants of these tumors (lymphocytoid, polygonal, fusiform and polymorphic) had the same general characteristics (age, sex, survival) and a similar clinical course. Grossly and histologically, the bronchial tumor, always located in proximal bronchial tree, largely involved the mediastinum. Metastases were peculiarly frequent to the liver (69%), to bone (64.2%) and to the central nervous system (36.2%). Three Schwartz-Bartter syndromes and two Denny Brown sensitive neuropathies were noted in this statistical study.

[Cardiac myxoma. Ultrastructural study of 2 cases]. / Myxome cardiaque. Etude ultrastructurale de deux observations

From amongst a series of eight cardiac myxomas, two were studied by electron microscopy, which enabled us to identify, amongst varous cell types, two main ones. One of these was a secretory cell with Golgi apparatus and secretory vacuoles, and the other was of the expected type, with microfilaments showing signs of progressive differentiation towards either muscle or epithelial structure. A morphological picture of this sort tends to lend support to the concept of a dysgenetic origin for these tumours, arising from pluripotent embryonic cells sequestrated in the region of the fossa ovalis.

[Constrictive pericarditis and Whipple's disease]. / Péricardite constrictive et maladie de Whipple.

The authors report the case of a 61 year-old patient treated by tetracycline for very probable Whipple's disease who developed constrictive pericarditis requiring pericardectomy. Although intestinal biopsy was negative, histological examination of the resected pericardium was very suggestive of a cardiac localisation of Whipple's disease, showing a fibrous pericarditis with a mononuclear infiltration including PAS-positive histiocytes. In addition, the same histological changes were found in a small fragment of myocardial biopsy. This case illustrates the prevalence and consequences of cardiac involvement in Whipple's disease.

[Intermediate and late changes in human cardiac graft]. / Modifications vasculaires semi-tardives et tardives du greffon cardiaque humain.

Chronic rejection, the most serious complication in long-term survivors of cardiac transplantation, was studied in 5 cardiac grafts obtained at retransplantation and in 15 post-mortem studies of patients who had survived 3 months to 10 years after transplantation. The usual clinical presentation was cardiac failure. Coronary angiography was performed in several cases and showed narrowing and non-opacification of small arteries often accompanied by thrombosis. Histology showed three types of vascular rejection: the most characteristic one, usually observed after the 6th month, was a stenosing fibrous endarteritis; another type of rejection, occurring earlier, was associated with acute myocardial rejection and presented as an inflammatory arteritis; the third type of vascular rejection was accompanied by widespread atheromatous lesions. The significance and pathogenesis of these lesions are discussed with respect to the clinical context with electron microscopic and immuno-histochemical data.

[Pathology of degenerative aortic valve insufficiency]. / Anatomie pathologique des insuffisances aortiques dégénératives.

The authors studies 154 cases of degenerative aortic regurgitation which presented macroscopically with atrophic changes of the valve and sometimes with hypertrophy and calcification. Histologically, the essential abnormality was the finding of mucopolysaccharide deposits dissociating the corpus spongiosa from the corpus fibrosa. Depending on the importance of these lesions, three degrees of severity can be defined, the most extensive (84% of our patient population) appearing to be typical of the disease. In addition, mild mitral valve prolapse (5%) and medial necrosis of the aortic wall (80% of patients undergoing aortic biopsy) were observed. These morphological features are on the whole quite different to those of other aortic valve pathologies (rheumatic, endocarditis). However, the border line with other pathologies with a similar anatomopathological substratum is less clearly defined: genetic abnormalities (Marfan's syndrome, Lobstein's disease, etc...) or age-related degenerative disease. The pathogenesis is not clearly understood but could be related to regional disturbances in collagen metabolism with collagenolysis predominating.

[Dystrophic aortic valve insufficiency]. / Les insuffisances aortiques dystrophiques.

Although dystrophic aortic regurgitation is considered to be a rare condition, if aortic regurgitation due to cystic media-necrosis which usually presents with annulo-aortic ectasia and regurgitation due to dystrophic aortic valves are included, it becomes a relatively common cause of aortic regurgitation. In the authors' experience of 313 patients operated for pure chronic aortic regurgitation, approximately 30% had dystrophic lesions and this was the second most common cause of aortic regurgitation after acute rheumatic fever. The clinical presentation is variable: excluding annulo-aortic ectasia, the other features of dystrophic aortic regurgitation are less well known. Eighty-nine cases without aneurysm of the ascending thoracic aorta were recensed and analysed in a French Cooperative study. They were divided into two groups with respect to the diameter of the ascending aorta measured by echocardiography. The incidence of late postoperative complications of the ascending aorta was higher in patients with a dilated aorta. The diagnosis of dystrophic aortic regurgitation is easy in patients with an aneurysm of the ascending aorta: in other cases, transoesophageal echocardiography is very useful for evaluating the valvular lesions. Surgical treatment of pure dystrophic aortic regurgitation with an aneurysm of the ascending aorta is well established but the best management of aortic regurgitation associated with only mildly dilated aorta is debatable.