The fasciitis-panniculitis syndrome presenting as complex regional pain syndrome type 1: report of a case.

A 28-year-old man presented with a clinical picture suggestive of complex regional pain syndrome type I following a blow to the thenar eminence and thumb. Symptoms, including swelling of the hand and distal forearm, progressed until an amputation was carried out to rid the patient of an unendurable painful and nonfunctioning wrist and hand. The histologic evaluation of the amputation specimen showed: 1) dermal edema, perivascular dermatitis, and epidermal hyperkeratosis; 2) subcutaneous chronic inflammation with subtotal replacement of the adipose lobules by fibrous tissue associated with thickening of the muscular fascia, implying the fasciitis-panniculitis reaction pattern; 3) atrophy, degeneration, necrosis, and focal calcifications of the skeletal muscles; 4) phlebosclerosis, phlebectasias and lymphocytic arteritis; and 5) increased cortical porosity of the bones. It seems that the pathogenetic process underlying the fasciitis-panniculitis syndrome may rarely manifest as a complex regional pain syndrome-like disorder.

The fasciitis-panniculitis syndromes. Clinical and pathologic features.

The authors propose to encompass under the designation of "fasciitis-panniculitis syndromes" (FPS) a group of disorders characterized by induration of the skin due to chronic inflammation and fibrosis of the subcutaneous septa and muscular fascia. The prototype of the FPS is eosinophilic fasciitis. Thirty-two consecutive patients with FPS were cared for at the author's hospital during a 10-year period. The association of the FPS with other diseases, clinical presentations, histologic features, and response to treatment were analyzed. Idiopathic FPS, that is, eosinophilic fasciitis, was diagnosed in 14 patients. In the remaining 18 cases, the FPS were ascribed to vascular disorders (n = 6), infections (n = 6), and neoplastic disorders (n = 3), while trauma, insect bites, and Sweet syndrome antedated the FPS in 1 patient each. The lesions had a sleeve-like distribution in 20 patients, plaque-like distribution in 7, and a combined pattern in 5. Skin biopsies revealed lesions in the deep subcutaneous layers with the pathologic triad of septal and fascial fibrosis, chronic inflammatory infiltration, and small-vessel vasculopathy. Spontaneous improvement occurred in 4 cases. Following cimetidine monotherapy, complete remission was achieved in an additional 3 of 5 patients. The concept of the FPS serves to advance our understanding on several fronts: emphasizing the clinical and etiologic diversity; recognizing a stereotypic tissue reaction pattern; highlighting the panniculitis in addition to the fasciitic component; and describing a similar response to drug therapy in different clinical settings. Based on the results of the present series, cimetidine may be recommended as first-line treatment.

Dirofilaria repens infection in northern Israel.

The fourth case of zoonotic Dirofilaria repens infection in Israel is reported, and the diagnostic morphologic characteristics of this filariid are reviewed. The importance of the exact anatomic diagnosis of this filaria is stressed in view of the fact that Israel has pockets of settlers from East Africa, a region endemic for lymphatic filariasis (Wuchereria bancrofti). Since the possibility of introduction of such an infection into the country exists, differentiating this zoonotic Dirofilaria from other filarial worms is essential. The clinicopathological features of a Dirofilaria repens infection are distinct. The patient initially has a painful subcutaneous or conjunctival swelling; the excisional biopsy shows the presence of a dead or alive, usually female worm that measures 220-660 microns across; the central intestine and the genital organs (two uteri) are located in the pseudocoelom; the thick, multilayered cuticle is provided with 95-105 sharp, longitudinal ridges, the latter being separated from each other by a distance of 12 microns; the circumferential muscle cell layer, covering the inner side of the cuticle, is bilaterally interrupted by the large chord cells, two to five nuclei of which are discernible in each cross section.

Acute lipase-induced panniculitis in rats with ligated veins of the hindlimb: a contribution to the role of acute panniculitis as a precursor of lipodermatosclerosis of venous disease.

The authors studied the effect of ligation of the femoral and saphenous veins on the evolution of lipase injection-induced subcutaneous fibrosis and inflammation in the rats' hindlimbs. The superficial muscular fascia was thickened and the number of veins was increased 3 days and 3 weeks after vein ligation; both abnormalities disappeared 6 weeks postoperatively. Vein ligation did not quantitatively affect fascial thickening or fibrosing panniculitis in hindlimbs injected with lipase 6 weeks prior to sacrifice. The results contradict the proposition that lipase-induced injury of rats' subcutaneous tissues compromised by venous stasis may lead to a persistent chronic inflammation and fibrosis of the subcutaneous-fascial complex duplicating lipodermatosclerosis in man.

Computer-assisted image analysis can aid the prognostication of advanced-stage neuroblastomas.

PURPOSE: The aim of this work was to detect nuclear parameters related to the prognosis of patients with stage III, IV or DS neuroblastomas. METHODS: Histological sections of 25 operation specimens obtained from children with advanced-stage neuroblastomas were subjected to computer-assisted image analysis. Statistical relationships between nuclear descriptors of the tumor cells and patients' clinical outcome were determined. RESULTS: The coefficient of variability of the mean nuclear area the mean nuclear elongation factor, and the mean nuclear averaged Feret diameter of the neuroblastoma cells were ascertained to be discriminators separating high-grade from low-grade tumors. CONCLUSIONS: The histomorphometrically gauged nuclear parameters may help oncologists to assess the prognosis of patients with advanced-stage neuroblastoma.

Bowel perforation due to gastrointestinal autonomic nerve tumour associated with neurofibromatosis type 1.

Gastrointestinal autonomic nerve (GAN) tumours form a distinct subcategory of gastrointestinal stromal tumours, and are thought to originate from the enteric autonomic plexus. To date, a total of 45 cases have been documented in the literature; a few of these cases were associated with neurofibromatosis type 1 (NF-1). Bowel perforation due to other gastrointestinal stromal tumours has been reported only twice, but never in association with a GAN tumour. We describe a 40-year-old woman with NF-1 who had bowel perforation due to a GAN tumour. The patient underwent radical surgical resection and remained tumour free for at least 4 years, which may indicate a good prognosis.

Osteoarthritis-like disorder in rats with vascular deprivation-induced necrosis of the femoral head.

The reparative processes following vascular deprivation-induced necrosis of the femoral head were studied histologically in rats sacrificed 2, 7, 14, 21, 42 and 92 days postoperatively. The blood supply was severed by incision of the periosteum at the neck of the femoral head and transection of the ligamentum teres. Granulation tissue and a well-vascularized fibrous tissue originating from the joint capsule invaded the necrotic marrow spaces. With progressive resorption of the necrotic tissues and osteoneogenesis, both appositional and intramembranous, within the fibrotic intertrabecular spaces, the remodeling process led to a shift of the normal spongy architecture of the femoral head to a compacta-like one. In a few cases, osseous bridges bisected a necrotic physeal cartilage at the latest time intervals. The remodeling was associated with flattening of the femoral heads as well as with degenerative, regenerative and reparative alterations of the articular cartilage. In one of the two femoral heads obtained three months postoperatively, cystic spaces developed in the fibrous subchondral zone. Our findings are consistent with the view that ineffective attempts at restoring the prenecrotic state of the femoral head by replacing the necrotic with viable tissue triggers the collapse of the femoral head. Thickening and condensation of the subchondral bone, leading to increased stiffness of the subchondral zone, result in the osteoarthritis-like disorder. Mimicking the well-known phases of human osteonecrosis, the model readily allows for preclinical studies of therapeutic regimens.

Lymph-node-based malignant lymphoma and reactive lymphadenopathy in eosinophilic fasciitis.

BACKGROUND: Lymph node enlargement in patients with eosinophilic fasciitis is a rare occurrence and its clinical significance is unknown. METHODS: The literature and authors' registries were searched for eosinophilic fasciitis associated with lymphadenopathy. Clinical data, time sequence of appearance of either disorder, and pathological diagnoses were analyzed. RESULTS: Six patients presenting with eosinophilic fasciitis had a lymph-node-based lymphoma and 4 patients had a reactive lymphadenopathy. The patients with lymphoma were elderly and the subcutaneous induration preceded the lymphadenopathy by 2 to 36 months. The patients with eosinophilic fasciitis and reactive lymphadenopathy were young and the onset of subcutaneous induration and lymph node enlargement coincided with one another. Favorable response of the eosinophilic fasciitis to prednisone therapy was attained in 3 of 3 patients with reactive lymphadenopathy and in 4 of the 6 cases with lymphoma. CONCLUSIONS: Eosinophilic fasciitis is rarely associated with clinically significant lymph node enlargement. Subcutaneous induration preceding the lymphadenopathy by 6 months or more, especially in elderly patients, suggests an underlying lymphoma. A favorable response of the subcutaneous induration to prednisone treatment does not exclude the diagnosis of lymphoma; therefore, it does not supersede the need of a pathological evaluation. A lymph node biopsy is mandatory in all cases.

Cellular dysplasia in acquired cystic renal disease: comparison of histomorphometrically gauged nuclear parameters in normal kidneys, renal cell carcinomas and acquired cystic kidneys.

Nuclear parameters were assessed by computer-assisted image analysis in the cells of abnormal epithelial formations in the acquired cystic kidneys of two dialysis patients, the proximal and distal tubules of a normal kidney and two well differentiated renal cell carcinomas. One acquired cystic kidney contained many small clear celled foci and am 0.9 cm-size clear celled lesion and the second one a papillary microadenoma. The clear celled lesion was cytologically indistinguishable from the carcinomas. The histomorphometrically gauged nuclear parameters were maximal and minimal ferret diameters, averaged ferret diameter, aspect ratio, shape factor, area, volume and specific length and width. Statistical evaluation evidenced that the nuclear area, volume, aspect ration and shape factor allowed for the distinction between benign and malignant epithelial structures. The medians of the nuclear parameters of atrophic tubules, cysts, clear celled foci, papillary adenoma and clear celled lesion in the two acquired cystic kidneys deviation from those of normal renal tubules and in, increasing order of disparity, approached those of the carcinomas.

Comparative study of computer-assisted image analysis and light-microscopically determined estrogen receptor status of breast carcinomas.

BACKGROUND: Efficient tamoxifen treatment of breast cancer patients depends on the degree to which pathologists are consistently able to use the so-called "modified quickscore" method to differentiate between negative and low-grade positive scores based on the current four-grade scale of the estrogen receptor (ER) status of the tumors. OBJECTIVE: To quantitatively test pathologists' ability to adequately render correct readings of the ER status of breast tumors. METHODS: The ER status of breast carcinomas was estimated by two pathologists and measured by computer-supported analysis in sections stained with ER antibody by the immunoperoxidase technique. Levels of agreement between the examiners' semiquantification and histomorphometrically gauged measurements were compared statistically. RESULTS: The kappa coefficients were 0.28 on a case-by-case collation of the grades of nuclear staining, 0.52 on applying binary categories of positively versus negatively stained cell nuclei, and 0.89 using binary categories with a weighted score of 1.2 to separate ER-negative from ER-positive breast carcinomas. CONCLUSIONS: The findings suggest that an optimum rating system is achieved by assigning tumors with a weighted score of 1.2 or less to the ER-negative and those with a weighted score of 1.3 or more to the ER-positive category of breast carcinomas.

Localized nodular myositis. A paraneoplastic phenomenon.

Localized nodular myositis was recognized in an elderly man six months prior to the diagnosis of Hodgkin's disease. Meticulous search of the muscle specimen failed to disclose tumorous involvement. The possible paraneoplastic nature of localized nodular myositis in this patient is discussed.

Experimentally gained insight - based proposal apropos the treatment of osteonecrosis of the femoral head.

An impeded blood flow through the femoral head is incriminated in the etiopathogenesis of osteonecrosis of the femoral head. The disorder is either primary (idiopathic avascular osteonecrosis) or secondary to one condition or another, say, corticosteroid medication, fracture of the neck, coagulation defects, physical or thermal damage, storage disorders, alcoholism, and infectious, autoimmune as also marrow infiltrating diseases. In the wake of the necrosis, several mediators are released in increased amounts, prime among which is the vascular endothelial growth factor. The intermediates recruit endothelial progenitor cells, macrophages, osteoclasts, fibroblasts, and osteoblasts, which, pervading throughout the necrotic areas, initiate the reparative processes. The dead, soft and hard tissular debris is substituted by fibrous - later on by hematopoietic-fatty tissue - and bone. The newly formed, appositional and intramembranous bone is deficient in its mechanical properties. The ordinary load-carrying functions suffice to deform these weakened femoral heads so that osteoarthritic changes develop. Considering contemporary assumptions of the causes of osteonecrosis, oxygenation, revascularization, and core decompression are the realistic therapeutic interventions. Necrosis of rats' femoral heads is studied as a model of osteonecrosis in both adults and children. In view of rodents' lifelong persisting physeal cartilage, vascular deprivation-induced osteonecrosis in rats mimics children's Perthes disease. The experimental model, which is well suited to test treatment modalities, has been used to investigate the effects of exposure to hyperbaric oxygen with and without non-weight bearing, medication of enoxaparin, and creation of an intraosseous conduit on the remodeling of the avascular necrotic femoral head. Intriguingly, the shape of treated rats' femoral heads is disfigured to a greater degree than that of untreated animals. This is most likely due to the reduced yield strength and elastic modulus as well as the raised strain-to-failure of the recently formed bone making up the post-necrotic femoral heads. It follows that expedited osteogenesis is, counter intuition, detrimental to maintaining the hemispherical shape of the femoral head, and thus to an articulation with congruent load-bearing surfaces. If this is indeed the case, the remodeling of the necrotic femoral head should be delayed, rather than sped up, as the present day paradigm would have it. Bearing in mind that the dead osseous structures keep their mechanical attributes for quite a while, a slowed down new bone formation would favor the gradual replacement of the necrotic by living bone. Therefore, management of the adult patients with osteonecrosis and children with Perthes disease should focus on a slowly progressive substitution so that the decline of the bone's mechanical properties is kept to a minimum. One viable therapeutic mode is a medication of inhibitors of the vascular endothelial growth factor.

Salivary gland double tumor: synchronous ipsilateral pleomorphic adenoma and acinic cell carcinoma of the parotid gland.

A 44-year-old woman underwent a partial parotidectomy for a slowly enlarging parotid mass diagnosed by fine needle aspiration biopsy as a pleomorphic adenoma. Though macroscopically recognized to be composed of two nodules, differing to some extent from one another, the mass appeared to constitute a single tumor. The microscopic examination disclosed two disparate neoplasms, which were separated from each other by a thin fibrous band. The larger of the two nodules was a pleomorphic adenoma and the smaller one an acinic cell carcinoma. The metachronous--and, even more, the synchronous--occurrence of two histologically different tumors in one major salivary gland is an exceptional and probably coincidental event.

Postosteonecrotic osteoarthritis-like disorder of the femoral head of rats.

The femoral heads of 15 rats were studied histologically 3 months after the induction of ischaemic necrosis by incising the cervical periosteum and cutting the ligamentum teres. The epiphyses consisted of immature disorganized subchondral and trabecular bone. The inter-trabecular spaces contained fibrous or haematopoietic tissue. Residual necrotic bone was rare. There was marked osteoblastic and osteoclastic activity. The articular aspect of the heads showed a spectrum of changes, ranging from cartilaginous degeneration with fibrillation and loss of glycosaminoglycans to an eburnated and polished bony surface. In seven rats, transphyseal bridges connected the epiphyseal and metaphyseal bony trabeculae to each other. It is suggested that the postnecrotic reparative processes, including the resorption of the necrotic debris and its replacement by newly formed, weak bone, led to an osteoarthritis-like disorder. This healing pattern of the necrotic femoral head was reminiscent of the progressive remodelling that occurs in rings in femoral capital osteonecrosis of adult human patients and in Perthes's disease of children.

Squamous cell carcinoma of the lung presenting with cutaneous leukocytoclastic vasculitis: a case report.

An elderly patient with paraneoplastic cutaneous leukocytoclastic vasculitis (CLV) leading to the discovery of an as-yet asymptomatic, potentially surgically curable squamous cell carcinoma of the lung is presented. This type of vasculitis has not been previously described in association with this type of lung cancer. Since vasculitic paraneoplastic syndromes, including CLV, may develop before the clinical presentation of malignant tumors, the present case and others previously reported strongly suggest that in apparently idiopathic CLV, patients should be evaluated for the presence of occult malignancy that could be curable by early detection.

Status of intraoperative cytology in the diagnosis of epithelioid hemangioma.

Whereas evaluation of the frozen section of a subcutaneous retro-auricular mass was equivocal, the correct diagnosis of epithelioid hemangioma could be suggested on examination of intraoperative cytological smears. It is proposed that in the absence of cytological cues of malignancy and in the presence of the proper clinical setting, the constellation of vascular structures, eosinophils, lymphocytes, and clusters of cuboidal cells with vacuoles in their abundant acidophilic cytoplasm is indicative of epithelioid hemangioma.

Computer-assisted image analysis of small cell lymphoma of the thyroid gland. Comparison of nuclear parameters of small lymphocytes in lymphomas and Hashimoto's thyroiditis.

The nuclear parameters of the small lymphocytes in nine cases of small cell lymphomas of the thyroid gland and 17 cases of Hashimoto's thyroiditis were assessed by computer-assisted image analysis. The nuclear area, maximal, minimal and averaged Ferret diameters, perimeter, regularity factor and elongation factor were gauged. Statistically, the nuclear area was ascertained to be the optimum descriptor discriminating between small neoplastic and reactive lymphocytes. Application of a novel variable, combining a nuclear area cut-off value of 14 microm2 with a nuclear averaged Ferret diameter cut-off value of 4.5 micron, allows for the distinction - with a high degree of sensitivity and specificity - between small neoplastic lymphocytes in thyroidal lymphomas and the reactive lymphocytes in Hashimoto's thyroiditis.

Histologic analysis of the periprosthetic tissues of long-term surviving cemented total hip arthroplasties.

Qualitative and semiquantitative features of the interfacial membranes of five long-term (> 16 years) surviving cemented total hip arthroplasties (four revision cases and one autopsy case) were compared with those of thirty short-term surviving (< 15 years) cemented hip prostheses. Cement granulomas, micron-sized polyethylene particles-induced giant-celled granulomas, sheets of submicron-sized polyethylene particles-laden macrophages, and aggregated, metallic particles-laden macrophages were scattered in the fibrous tissue of all interfacial membranes. Quantitatively, characteristics of the interfacial membranes of the two groups differed from one another. The dominant species of prosthetic debris in the interfacial membranes of the short-term surviving joint replacements was derived from the polyethylene acetabular socket, and, correspondingly, giant-celled granulomas and macrophagic sheets predominated. Metallic particles and the macrophagic reaction thereto dominated in the interfacial membranes of the long-term surviving arthroplasties, and large cement and polyethylene chunks typically were incorporated in the fibrous tissue of the membranes without an accompanying macrophagic response. In long-term surviving hip arthroplasties, metallic particles may be at least as important as polymeric detritus in stimulating the formation of the bone-resorbing, granulomatous interfacial membrane, which is the hallmark of aseptically loosened arthroplasties. Differences in mechanical settings may account for unlike modes and rates of generation of prosthetic breakdown products, explaining the disparate survivorship of different patients' artificial joints.

The histologic features of the interfacial membrane of intramedullary nails.

Thirty-six interfacial membranes collected at the time of removal of intramedullary L316 stainless steel nails were studied histologically. The membranes consisted of bland fibrous tissue in a minority of cases. Most often, the nails were enclosed within a synovial-like membrane. Palisading macrophages and fibroblasts abutted on the metallic surface of the nails. Foreign body giant-celled granulomas were scattered in the midzone of the membranes, mono- and polykaryonic macrophages having phagocytozed small metallic particles, necrotic bony debris, and, sometimes, lipidic compounds. Aggregates of hemosiderin-containing macrophages occasionally marked the sites of previous hemorrhages. When present in the retrieved specimen, the bone underlying the membrane was undergoing remodeling. Interfacial motion, consequent on dissimilar stiffness of the bone and nail, as well as deposition of metallic and bony debris, are likely responsible for the formation of the synovial-like interfacial membrane.

Transphyseal osseous bridges in experimental osteonecrosis of the femoral head of the rat. Histologic study of the bony bridges connecting the epiphyseal with the metaphyseal bony trabeculae through gaps in the physeal cartilage.

In view of the lifelong persistence of the physis, the femoral head of rats may serve to model Perthes disease and slipped capital femoral epiphysis. To produce osteonecrosis, the blood supply of one femoral head of 133, 6-month-old animals was severed by circumferentially incising the periosteum of the neck and cutting the ligamentum teres. The rats were killed 7 days to 90 days postoperatively. Associated with resorption of the necrotic bone and marrow, remodeling of the epiphysis was characterized by an ingrowth of vascularized fibrous tissue, formation of new bone and some cartilage, architectural deformation and flattening of the head. In 22 of 83 rats killed 30 days or more postoperatively, gaps in the continuity of the physeal cartilage were occupied by osseous bridges, connecting newly formed epiphyseal bony trabeculae with either the preexisting or newly formed metaphyseal osseous trabeculae. This healing mode may follow ischemic death of physeal chondrocytes or be owing to another mechanism, e.g., release of mediatory substances of inflammation. These findings raise the possibility that fixation of the healing epiphysis of a child's previously necrotic femoral head to the metaphysis occurs by transphyseal osseous growth in cases in which the physis is involved in the necrotic process.