Mammary sarcoidosis. Two cases and literature review

A patient with sarcoidosis had a biopsy of a firm nontender breast nodule that at analysis disclosed multiple noncaseating granulomas. In another patient with sarcoidosis, noncaseating granulomas were an incidental finding in a mastectomy specimen containing medullary carcinoma and in two subsequent biopsy specimens of the contralateral benign breast. Tests for acid-fast bacteria and fungi using special stains were negative in both cases. There are nine other histologically documented cases of mammary involvement with sarcoidosis. Since the lesions of mammary sarcoidosis often cannot be distinguished from those of carcinoma by physical examination, we suggest that clinically suspicious lesions undergo biopsy whether or not disseminated sarcoidosis is present.     

Aspiration biopsy of nodular sarcoidosis of the muscle

The nodular form of muscular sarcoidosis is rare and the condition is often confused with a soft tissue neoplasm. We present a case of nodular muscular sarcoidosis of the right calf in a 52-yr-old woman which was diagnosed by thin-needle aspiration biopsy (TNAB). In this patient, a calf mass was the initial manifestation of sarcoidosis. Contrast-enhanced computed tomographic scans of the calf showed a mass with peripheral ring-like enhancement. T2-weighted magnetic resonance images demonstrated a mass with central hypointensity and marked peripheral hyperintensity. TNAB revealed noncaseating epithelioid cell granulomas in association with multinucleated giant cells. Combined with the radiologic findings, TNAB is considered a useful modality for the diagnosis of nodular muscular sarcoidosis.     

Matrix metalloproteinases and their tissue inhibitors in the lesions of cardiac and pulmonary sarcoidosis: an immunohistochemical study

The pathogenesis of the tissue damage and fibrosis in sarcoidosis is poorly understood. The matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) must be considered in this regard, because they control the lysis of connective tissue components. Immunohistochemical studies (peroxidase and dual labeling for confocal microscopy) of reactivity for MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and the 4 membrane-type-MMPs were made on tissues from patients with cardiac (n = 4) and pulmonary (n = 5) sarcoidosis. The granulomas were histochemically similar in both organs. The multinucleated giant cells (MGCs) showed moderate reactivity for MMP-1 and MMP-9 and variable reactivity for MMP-2 and MMP-3; in addition, they showed colocalization of MT-1-MMP, which activates MMP-2. The reactivity of epithelioid cells (ECs) was moderate for MMP-2 and mild for other MMPs. Macrophages showed weaker reactivity for MMPs than did MGCs and ECs. All 3 types of cells showed very low reactivity for TIMPs. Staining for type IV collagen showed focal damage to the basement membranes of cardiac myocytes and pulmonary alveoli near the granulomas. The cells in sarcoid granulomas contain an abundance of MMPs and a paucity of TIMPs. The MGCs also contain MT-1-MMP and thus can activate MMP-2 in the granulomas. The MMPs can cause damage to adjacent cardiac myocytes and pulmonary alveoli, leading to the interstitial fibrosis produced by sarcoidosis.     

Therapeutic response to thalidomide in Melkersson-Rosenthal syndrome: a case report.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown etiology characterized by a triad of symptoms: recurrent orofacial swelling, relapsing facial palsy. and a fissured tongue. A differential diagnosis must be made with other granulomatous diseases, such as sarcoidosis and oral Crohn disease; however, the histologic findings of noncaseating, sarcoidal granulomas support the diagnosis of MRS. RESULTS: Many therapeutic modalities have been described for this disease. In this case report, we present a patient with MRS that was treated with thalidomide because of the identification of tumor necrosis factor a in the lesion by immunohistochemical analysis. This is the first reported detection of tumor necrosis factor a in an MRS lesion, as well the first reported use of thalidomide to treat this clinical condition.     

A case of sarcoidosis revealed in the course of IgA nephropathy

A 36 year old man, who had been proteinuric for 14 years due to immunoglobulin A (IgA) nephropathy, was admitted because of an acute exacerbation in renal dysfunction with hypercalcemia. He had presented with aortic regurgitation and increased pulmonary marking by chest X-ray, but laboratory examinations had failed to make an exact diagnosis, On admission, noncaseating epithelioid granulomas were disclosed by muscle and skin biopsies. Ophthalmological evaluation revealed old uveitis and retinal changes conslstent with sarcoidosis. In this case, IgA nephropathy was thought to be the initial manifestation of sarcoidosis that developed latently. Sarcoidosis should be considered in a differential diagnosis of IgA nephropathy.     

Sarcoidosis presenting initially as breast mass: report of two cases

The cases of two patients who presented with breast masses suggesting carcinoma and no other clinical features of sarcoidosis are reported. Biopsies in both patients revealed noncaseating, epithelioid granulomas. Mycobacteria, fungi, and foreign material were not identified. In one of the patients, other sites of involvement were discovered five years later. These cases illustrate that sarcoidosis should be considered in patients with granulomatous breast disease, even without evidence of disease elsewhere.     

Intrahepatic bile duct destruction in a patient with sarcoidosis and chronic intrahepatic cholestasis

An autopsy case of sarcoidosis with chronic intrahepatic cholestasis for 2 and a half years was presented. Generalized distribution of noncaseating epithelioid granulomas and positive Kveim test were consistent with sarcoidosis. Histological examination of the liver revealed extensive bile duct destruction similar to that seen in the liver of primary biliary cirrhosis. Destructive cholangitis found in the liver appeared to be responsible for long term intrahepatic cholestasis, and no sarcoid granulomas in the liver were found to destroy any bile duct. The possible relation in pathogenesis of the bile duct destruction between primary biliary cirrhosis and sarcoidosis was discussed.     

INTRAHEPATIC BILE DUCT DESTRUCTION IN A PATIENT WITH SARCOIDOSIS AND CHRONIC INTRAHEPATIC CHOLESTASIS

An autopsy case of sarcoidosis with chronic intrahepatic cholestasis for 2 and a half years was presented. Generalized distribution of noncaseating epithelioid granulomas and positive Kveim test were consistent with sarcoidosis. Histological examination of the liver revealed extensive bile duct destruction similar to that seen in the liver of primary biliary cirrhosis. Destructive cholangitis found in the liver appeared to be responsible for long term intrahepatic cholestasis, and no sarcoid granulomas in the liver were found to destroy any bile duct. The possible relation in pathogenesis of the bile duct destruction between primary biliary cirrhosis and sarcoidosis was discussed.     

伴反应性肉芽肿的乳腺癌

目的：研究伴反应性肉芽肿的乳腺癌的临床病理特点。方法：观察5例伴反应性肉芽肿的乳腺癌的形态学改变。结果：5例病人都没有全身性肉芽肿性疾病。癌组织内均可见非干酪性肉芽肿,肉芽肿沿癌细胞分布,其内有朗汉斯多核巨细胞区域性淋巴结内没有反应性肉芽肿。结论：伴反应性肉芽肿的乳腺癌需要和乳腺伴破骨细胞样巨细胞的瘤、伴破骨细胞样巨细胞的化生性癌、肉芽肿性小叶性乳腺炎、间质反应性巨细胞、伴结节病或伴结核病的癌鉴别。     

Sarcoidosis diagnosed on fine-needle aspiration cytology of salivary glands: a report of three cases

Three female patients, two presenting with bilateral parotid gland enlargement and one with bilateral submandibular gland enlargement, were subjected to fine-needle aspiration cytology (FNAC). Smears showed noncaseating epithelioid cell granulomas with or without giant cells and salivary gland acini with varying degrees of degenerative changes. After excluding other granulomatous lesions, sarcoidosis was suggested and was subsequently proved in all three cases. FNAC, therefore, may be considered a useful diagnostic modality in cases of sarcoidosis presenting primarily with head and neck involvement.     

Renal insufficiency in sarcoidosis. A clinical and pathologic study

The relationship of sarcoidosis to renal insufficiency is not widely known by pathologists or clinicians. During an 8-year period beginning in 1980, we observed six patients with sarcoidosis and clinically significant renal insufficiency (serum creatinine, greater than 260 mumol/L). In one of these patients with long-standing sarcoidosis, renal insufficiency was attributed to unrelated primary renal disease until renal biopsy specimen showed interstitial noncaseating granulomas. The four patients with renal insufficiency at presentation differed from the typical patient with sarcoidosis because they were white men who lacked the usual clinical constellation of skin, eye, and pulmonary involvement. All four had noncaseating granulomas on their initial biopsy (bone marrow [3 patients], and lymph node [1 patient]), suggesting each had sarcoidosis, yet each had two or more follow-up biopsies before the diagnosis of sarcoidosis was accepted and appropriate therapy initiated. One of these four patients underwent long-term antifungal and antituberculous therapy. The major causes of renal insufficiency in these six patients were complications of hypercalcemia and interstitial granulomatous nephritis. Except in one patient with nephrocalcinosis, prednisone therapy resulted in a dramatic fall in serum creatinine level with resolution of hypercalcemia. Sarcoidosis is a rare, but treatable, cause of renal insufficiency. Early recognition by clinicians and pathologists may spare patients from undergoing unnecessary biopsies and result in more timely initiation of therapy.     

Sarcoidosis

Sarcoidosis is a systemic disorder of unknown aetiology characterised by noncaseating granulomas leading principally to bilateral hilar lymphadenopathies, pulmonary infiltration and skin and eye lesions. Sarcoidosis may involve other organs, including peripheral lymph nodes, liver, spleen, nervous and musculoskeletal systems, heart, ear, nose and kidney. Although the clinical involvement of liver and heart is relatively uncommon, hepatic and cardiac granulomas are present at autopsy in about 70 to 80% and 25 to 50%, respectively, of patients with this disease. The diagnosis of sarcoidosis includes compatible clinical and/or radiological presentations and histological evidence of noninfectious and noncaseating epitheloid cell granulomas in the absence of other identifiable agents responsible for such histological lesions. Disease course is variable and usually characterised by frequent remissions, but it may become progressive and chronic in a small percentage of patients. The optimal treatment of sarcoidosis remains poorly defined. In patients with progressive pulmonary dysfunction as well as in those with severe extrapulmonary localisations, systemic corticosteroids usually represent the first approach, limited by long term toxicity and frequent relapses after treatment interruption. In the presence of refractory or corticosteroid-dependent forms of the disease, antimalarial drugs or low dosage methotrexate may be used with prolonged benefit. The indications for immunosuppressive agents such as azathioprine, chlorambucil, cyclophosphamide and cyclosporin are uncommon and limited because of potentially serious adverse effects and lack of information on their long term efficacy. In the case of ocular and limited cutaneous manifestations, local corticosteroid therapy may be useful.     

Sarcoidosis with pulmonary hypertension exacerbated by Takayasu-like large vessel vasculitis

A 72-year-old male visited the hospital with a complaint of dyspnea. Under the diagnosis of pulmonary hypertension (PH) due to chronic thrombotic and/or embolic disease, this patient received anti-coagulant therapy. Unfortunately, the respiratory state deteriorated and died 34 days after admission. At autopsy, noncaseating granulomas, which were diagnostic of sarcoidosis, were found in bilateral enlarged hilar lymph nodes, lungs, heart, liver, spleen, testis and epididymis. In pulmonary vasculature, the following three kinds of lesions were observed; (i) sarcoid granulomatous vasculitis at the peripheral arteries and veins, (ii) intimal fibrous lesions ubiquitously found in proximal and peripheral arteries which were thought to be organized thromboemboli, (iii) Takayasu-like large vessel vasculitis with a huge fresh mural thrombus narrowing the lumen of most proximal portion of right pulmonary artery. Autopsy findings indicate that chronic sustained PH state in this patient was attributable to thrombotic and/or thromboembolic disease, and Takayasu-like vasculitis with thrombus played a role in the final deterioration of respiratory state through exacerbation of PH. In sarcoidosis patients, vasculitic lesions which can be formed in both small and large pulmonary arteries must be raised as the differential diagnosis for the initial cause of PH as well as the accelerating factor of PH.     

Cardiac sarcoidosis: a comprehensive review

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas in involved organs. Organs involved with sarcoidosis include lymph nodes, skin, lung, central nervous system, and eye. Only 40-50% of patients with cardiac sarcoidosis diagnosed at autopsy have the diagnosis made during their lifetime. Cardiac sarcoidosis can manifest itself as complete heart block, ventricular arrhythmias, congestive heart failure, pericardial effusion, pulmonary hypertension, and ventricular aneurysms. Diagnostic tests such as the electrocardiogram, two-dimensional echocardiography, cardiac magnetic resonance imaging, positron emission tomography scan, radionuclide scan, and endomyocardial biopsy can be helpful in the early detection of cardiac sarcoidosis. Considering the increased risk of sudden death, cardiac sarcoidosis is an indication for early treatment with corticosteroids or other immunosuppressive agents. Other treatments include placement of a pacemaker or implantable defibrillator to prevent sudden death. In refractory cases, cardiac transplantation should be considered.     

Hepatic granulomas: a clinicopathologic analysis of 86 cases

The aim of this study was to determine the prevalence and histopathological characteristics of hepatic granulomas.All records of liver biopsies/resections evaluated in our pathology department between 2002 and 2009 were retrospectively reviewed. Specimens with hepatic granulomas were reexamined by a designated pathologist. Type and localization of granulomas, size of granulomas and epithelioid histiocytes, and the morphological findings of surrounding liver tissue were recorded in an attempt to establish a correlation with relevant clinical, laboratory and radiological findings.Out of 1420 liver biopsy/resected specimens evaluated at our institution during the study period, 86 cases of epithelioid cell granulomas (6.05%) were observed. Of the 86 cases, 23 were men and 63 were women. The most common underlying etiology was PBC in 38 patients, infections in 34, malignancies in five, sarcoidosis in four, and foreign bodies in three patients. One case (1.2%) of a drug-induced hepatic granuloma was encountered, while another case was deemed idiopathic (of unknown etiology). Contrary to common belief, granulomas were observed not only in early stage PBC but also in cases with stage 3 disease. Out of all the PBC cases with granulomas, 55.6% had stage 3 disease, and besides periductal granulomas, intraacinar granulomas were also seen. For sarcoidosis, intra- and peri-granulomatous fibrosis was observed in as many as 75% of cases. A large majority of granulomas (82.4%) associated with infections were of the necrotizing type.Extensive evaluation of the morphological characteristics of hepatic granulomas and surrounding liver tissue along with clinical, radiological, and other laboratory findings may help arrive at an accurate diagnosis in a majority of cases. Rather than being a final diagnosis, the presence of hepatic granulomas entails the need for further investigations towards identifying the underlying etiology, with a pathologist being at the center of the diagnostic process.     

Sarcoidosis of the testis: a case report

A left testicular mass was found in a 34-year-old black man with a history of multisystem sarcoidosis of 7½ years duration. Microscopic examination of the excised testicle revealed noncaseating granulomas throughout, as well as a few such lesions in the epididymis. This is the seventh reported, microscopically proven case of sarcoidosis of the testis without significant epididymal involvement occurring in a living individual.     

Treatment of Pulmonary Sarcoidosis

More than a century ago, Jonathan Hutchingson, a surgeon-dermatologist, identified the first case of sarcoidosis at King's College, London. The disease is now known as a commonplace multi-system disorder characterised by the formation of noncaseating granulomata. The diagnosis of sarcoidosis is established by recognising clinicoradiological findings and providing histological evidence of noncaseating granuloma. Serum angiotensin converting enzyme levels are high in about two-thirds of the patients and hypercalcaemia is a feature in 1 of every 10 patients with sarcoidosis. Immunological abnormalities include depression of cutaneous delayed-type hypersensitivity, hyperactive B cells and the presence of circulating immune complexes. The course and prognosis of the disease usually correlate with the mode of onset. An acute onset with erythema nodosum indicates a good prognosis and spontaneous resolution, whereas an insidious onset may be followed by relentless, progressive fibrosis. Mortality and morbidity are caused by pulmonary fibrosis, cardiac arrhythmias, renal failure, neurological involvement and blindness. Corticosteroids and choloroquine relieve symptoms and suppress inflammation and granuloma formation.     

A case of Sj?gren's syndrome complicated by polymyositis and sarcoidosis with HLA-B7 and DR 8: common causes of susceptibility for these diseases]

We describe a case of a Japanese patient initially presenting with Sj?gren's syndrome who later developed polymyositis and sarcoidosis. A 67-year-old woman with a 4 month history of myalgia was admitted in April 1998 for examination. The patient had a 10 year history of symptoms consistent with Sj?gren's syndrome. A diagnosis of polymyositis was made based on a biopsy of the muscle and an electromyogram. Positive Shirmer and Rose Bengal tests and results of a minor salivary gland biopsy were all consistent with Sj?gren's syndrome. Chest computed tomography detected a bilateral hilar lymphadenopathy. Microscopic examination of a mediastinal lymph node demonstrated multiple noncaseating granulomas with multiple epithelioid cells and Langhans-like giant cells. A diagnosis of sarcoidosis was made based on these findings. Hepatitis C infection was also detected by elevated antibody levels. The patient was given 40 mg/day of oral prednisolone and a remission of her myositis and lymphadenopathy was obtained. The patient exhibited HLA-B7 and HLA-DR 8. HLA-DR 8 is commonly associated with these three disorders, and HLA-B7 is also associated with overlap syndrome in Japanese patients. The present case suggested the possibility of a common etiological background for these three disorders. Furthermore, the importance of genetic background, including HLA phenotype, in determining susceptibility to these disorders was demonstrated.     

Multiple myeloma in association with sarcoidosis

The association of sarcoidosis with Hodgkin disease and non-Hodgkin lymphoma is well known. However, multiple myeloma also can occur rarely in association with sarcoidosis. We describe a patient with sarcoidosis who subsequently developed multiple myeloma. The patient was a 49-year-old woman with a 4-year history of severe, chronic, active sarcoidosis involving her lungs, lymph nodes, eyes, and bone marrow. During the initial clinical workup, a serum monoclonal paraprotein was detected and bone marrow examination revealed a slight increase in plasma cells (4%), in addition to noncaseating granulomas. Thus, the diagnoses of monoclonal gammopathy of undetermined significance and sarcoidosis were established simultaneously. She sought medical attention for her current illness when she developed low back pain and weakness of her lower extremities. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin (Ig) G kappa type, and quantification revealed an IgG level of 46.67 g/L (normal, 5.88--15.73 g/L). Bone marrow aspiration and biopsy revealed multiple myeloma and sarcoidosis. Including this patient, 11 cases of sarcoidosis and multiple myeloma have been reported to date, including 3 patients with monoclonal gammopathy of undetermined significance preceding the onset of multiple myeloma. In this case, as in most of the cases reported previously, sarcoidosis preceded the development of multiple myeloma.