A case of epididymal sarcoidosis

We reported a case of epididymal sarcoidosis. The patient was a 13-year-old boy with a chief complaint of right scrotal mass. On physical examination, a firm, nontender 7 mm mass was palpable in the right hemiscrotum and appeared to involve the head of the epididymis. Ultrasonography showed a highly echogenic mass in the epididymis. A routine chest X-ray revealed lymphadenopathy of the mediastinum and reticular shadows in bilateral lung fields. Because the lesion might be confined to the epididymis, a partial epididymectomy was performed. The histopathologic specimen showed noncaseating granulomas consistent with sarcoidosis. Lung biopsies also revealed noncaseating granulomas. Subsequent pulmonary function studies revealed a mild obstructing ventiratory defect, therefore therapy was instituted with systemic steroids. There were no further recurrent scrotal masses. Although sarcoidosis is known to affect many organs, involvement of the genital system is relatively rare. Most of the patients with intrascrotal sarcoid lesions have an abnormal chest X-ray. We need to differentiate these lesions from advanced testicular cancer. This is the 5th case of intrascrotal sarcoidosis in Japanese literature.     

Muscular sarcoidosis: apropos of a case

We report the case of a 75-year old woman presenting sarcoid myopathy with pseudohypertrophy and skin involvement. Muscular biopsy confirmed the diagnosis of sarcoidosis. Symptomatic muscle involvement in sarcoidosis is rare. Three forms are described: myopathic, myositic and nodular. The relevance of imaging techniques is reviewed. Treatment is based on corticotherapy which is less efficient in myopathic form and in this case we had to use methotrexate with success.     

Cutaneous sarcoidosis treated with methotrexate

Sixteen patients with cutaneous sarcoidosis, 15 of whom also had involvement of other organs, were treated with methotrexate (MTX) orally once a week in an open study. The treatment period was from 1 to 72 months (mean 23 months). In 12 patients the skin lesions cleared, and in 3 of 4 patients who had sarcoid uveitis this cleared as well. The chest X-ray of 6 patients showed no corresponding improvement in pulmonary changes or in hilar adenopathy. Ten patients suffered side effects, usually nausea on the day MTX was taken. Two had transiently increased transaminase levels. Treatment was discontinued in 2 patients due to nausea. It is concluded that MTX is a useful alternative to systemically administered glucocorticoids in the treatment of disfiguring cutaneous sarcoidosis and sarcoid uveitis. The effect of MTX on hilar adenopathy and pulmonary sarcoidosis is uncertain.     

Mutations of the RET-GDNF signaling pathway in Ondine''s curse

Sarcoidosis is a multi-systemic granulomatous disease of unknown cause. It commonly involves lymph nodes, lungs, eyes, and skin. Cardiac sarcoid may be isolated, or associated with systemic involvement. Cardiac involvement is found in 20-50% of autopsied patients with sarcoidosis. However, it only gives rise to clinical manifestations in about 5% of patients. Cardiac involvement by sarcoid has been reported to manifest as complete heart block, papillary muscle dysfunction, congestive heart failure, pericarditis and/or effusion, conduction abnormality or arrhythmia, chest pain, and sudden death. The most common site of involvement is the interventricular septum base, which when involved may lead to heart block or arrhythmia. We report a case of sudden death in a 33-year-old male with a history of surgically repaired congenital heart disease. Although his congenital heart disease was originally postulated to be important in his death, autopsy examination revealed cardiac sarcoid with prominent involvement of the conduction system.     

Failure to detect the presence of Chlamydia pneumoniae in sarcoid pathology specimens

The pathogenesis of sarcoidosis is not yet known. On the basis of seroepidemiological data, an association between Chlamydia pneumoniae infection and sarcoidosis has been suggested, but so far no study has addressed the direct detection of this agent in the affected tissues. The aim of the present study was to detect C. pneumoniae deoxyribonucleic acid (DNA) within sarcoid tissue specimens by means of a two-step polymerase chain reaction. Lung biopsy specimens of 33 patients with histologically confirmed pulmonary sarcoidosis and 21 control lung biopsies or pathology specimens of patients with pulmonary carcinoma or emphysema were retrospectively analysed. A nested polymerase chain reaction was applied using two sets of primers designed to detect a fragment of the 16 strand ribosomal ribonucleic acid (rRNA) gene of C. pneumoniae. The results of the study failed to demonstrate the presence of C. pneumoniae in biopsy specimens of sarcoid tissue and in the control lung biopsies or pathology specimens. Our results, therefore, tend to rule out the possibility of a direct involvement of Chlamydia pneumoniae in the pathogenesis of sarcoidosis.     

Migration of the dominant pacemaker region in the rat sinoatrial node

"Early onset sarcoidosis" is a chronic granulomatous disease occurring in children younger than 5 years of age, and characterized by a classic symptom triad consisting of skin, eye and joint lesions, with on rare occasion pulmonary involvement. The disorder often goes unrecognized because of its rarity and, since polyarthritis and uveitis are the predominant symptoms, most of these children are misdiagnosed as having juvenile chronic arthritis (JCA). A child with erythema nodosum at 7 months of age, later diagnosed as JCA and definitively recognized as "early onset sarcoidosis" is reported. This case shows that, whenever possible, a biopsy showing the typical picture of sarcoid granulomas is crucial to distinguish these clinical conditions.     

The case for a heroin substitution treatment trial in Canada

A patient with malaise, uveitis and a nodular infiltrate in the left lower lobe of the lung is described. An open lung biopsy established the diagnosis of necrotizing sarcoid granulomatosis. The differential diagnosis of necrotizing sarcoid granulomatosis with sarcoidosis and angiocentric granulomatosis (Wegener's disease) is extensively discussed. Our case illustrates that NSG and sarcoidosis could be pathogenetically related.     

Cutaneous involvement in sarcoidosis. Relationship to systemic disease

Sarcoidosis is an antigen-mediated disease defined by granuloma formation in different organs. It involves mainly the mediastinal and peripheral lymph nodes, lungs, eyes, skin, liver, and spleen. Cutaneous lesions of sarcoidosis may be specific, showing histologically noncaseating granulomas, or nonspecific, most typically erythema nodosum. Frequently, both types of skin lesions are the means of presentation of the disease and may contribute to the diagnosis. A workup for systemic sarcoidosis should be undertaken in every patient with sarcoid cutaneous granulomas. Some types of cutaneous lesions have prognostic significance. Lupus pernio and plaques are associated with more severe systemic involvement and more chronic course, while erythema nodosum is the hallmark of acute and benign disease.     

Nuclear imaging. 67Gallium, 201thallium, 18F-labeled fluoro-2-deoxy-D-glucose positron emission tomography

67Gallium scan has been used for years in sarcoidosis as a marker of activity, a determiner of the extent and distribution of the disease, a diagnostic support, and an aid in therapeutic management. Because of its limited sensitivity and specificity for sarcoidosis, however, it is currently used mainly to assist in diagnosis in difficult cases, particularly in those with isolated extrathoracic sarcoidosis. The finding of the typical lambda or panda patterns supports the diagnosis and reinforces the indication to perform an appropriate biopsy or Kveim-Siltzbach test. In addition, the detection of clinically silent extrathoracic uptake may provide sites for biopsy. 67Gallium scans' routine use in the follow-up of pulmonary sarcoidosis under treatment has decreased because that is best accomplished by means of serial chest radiographs and PFT. 201Thallium scintigraphy studies the myocardial perfusion and is complementary to echocardiography and 24-hour electrocardiographic monitoring in the assessment of sarcoid cardiac involvement. It typically shows segmental areas of decreased uptake in the ventricular myocardium that disappear or decrease in size during stress or after intravenous administration of dipyridamole. That reverse distribution is not specific for cardiac sarcoidosis, however, because it may also occur in other cardiomyopathies. PET is based on the increase of glucose metabolism in inflamed tissues. It may have great potential to assess sarcoidosis activity, but it is still largely experimental and is not routinely employed.     

Etiology of sarcoidosis

Since sarcoidosis was first recognized as a distinct clinical entity, investigators have speculated that a transmissible agent may cause sarcoidosis. Recent attempts at directly isolating infectious organisms or indirectly detecting microbial DNA or RNA from sarcoid tissue have led to inconclusive results. Studies on the immunopathogenic origins of sarcoidosis have provided evidence of persistent antigenic stimulation at sites of inflammation that are associated with dysregulated cytokine production. To date, however, the challenge of defining the cause of sarcoidosis remains unmet.     

Human herpesvirus 8 variants in sarcoid tissues

BACKGROUND: The cause of sarcoidosis is unknown, although mycobacteria have been implicated. We examined sarcoid tissues for human herpesvirus 8 (HHV-8) in addition to mycobacterial genomic sequences. METHODS: Biopsy samples from 17 patients with sarcoidosis were studied (eight transbronchial, 27 lymph node, two skin, and two oral mucosa). We used tissues (n = 137) from 96 patients without sarcoidosis as negative controls. A nested PCR was applied to amplify a segment of open reading frame (ORF) 26 of the HHV-8 genome, and a heminested PCR was to amplify a segment of ORF 25 of HHV-8 and of the 16 S rRNA gene of mycobacteria. Differences in base sequences of the amplified fragments were resolved with single-strand conformation polymorphism and dideoxy sequencing. FINDINGS: HHV-8 ORF 26 DNA was detected in significantly higher proportions of sarcoid than of non-sarcoid tissue samples from lung (8/8 vs 0/54; p < 0.0001), lymph nodes (26/27 vs 6/29; p < 0.0001), skin (2/2 vs 0/17; p = 0.006), and oral tissues (2/2 vs 1/13; p = 0.029). 31 (82%) of the 38 ORF 26 DNA-positive sarcoid specimens were also positive for ORF 25 DNA. For mycobacteria-like 16 S rRNA DNA, the proportion positive was significantly higher in sarcoid than non-sarcoid tissues for lymph node samples (11/27 vs 2/29; p = 0.003) but not for other tissues (lung 3/8 vs 22/54; skin 2/2 vs 15/17; and oral tissues 1/2 vs 0/13). Overall, the prevalence of HHV-8 ORF 26 sequences was higher in sarcoid tissues than in non-sarcoid tissues (p < 0.0001). When patients whose tissues were included in a masked phase of the study were treated as units of analysis, eight of eight sarcoidosis patients were positive for HHV-8 ORF 26 DNA, compared with three of 56 control patients (p < 0.0001); for mycobacteria-like sequences, three of eight sarcoidosis patients were positive, compared with four of 56 controls (p = 0.0464). The HHV-8 ORF 26 sequences, ten of which were unique, could be segregated into four groups according to peptide motifs. In seven of nine patients from whom biopsy samples were taken from various sites, different sequences were recovered. The mycobacterial sequences amplified from sarcoid tissues were also varied, but none was homologous to those of known species. INTERPRETATION: Variant HHV-8 DNA sequences are found in a wide range of sarcoid but not non-sarcoid tissues. Mycobacteria-like 16 S rRNA sequences are more frequently present in sarcoid lymph nodes and not in other tissue types, but do not indicate infection by a particular mycobacterial species.     

Involvement of the IP-10 chemokine in sarcoid granulomatous reactions

The accumulation of T cells and monocytes at sites of ongoing inflammation represents the earliest step in the series of events that lead to granuloma formation in sarcoidosis. In this study, we evaluated the pulmonary production of IFN-inducible protein 10 (IP-10), a CXC chemokine that stimulates the directional migration of activated T cells. Striking levels of IP-10 were demonstrated in the bronchoalveolar lavage (BAL) fluid of 24 patients with pulmonary sarcoidosis and lymphocytic alveolitis, as compared with patients with inactive disease or control subjects. A positive correlation was demonstrated between IP-10 levels and the number of sarcoid CD45R0+/CD4+ cells in the BAL. Immunochemistry, performed with an anti-human IP-10 polyclonal Ab in lymph nodes displaying prominent sarcoid granulomas, showed that cells bearing IP-10 were mainly epithelioid cells and CD68+ macrophages located inside granulomatous areas. Macrophages recovered from the BAL of sarcoid patients stained positive for IP-10 protein. Furthermore, alveolar macrophages isolated from sarcoid patients with T cell alveolitis and cultured for 24 h in presence of IFN-gamma secreted definite levels of IP-10 capable of inducing T cell chemiotaxis. Interestingly, alveolar lymphocytes recovered from patients with active sarcoidosis were CD4+ T cells expressing Th1 cytokines (IL-2 and IFN-gamma) and high levels of CXCR3. Taken together, these data suggest the potential role of IP-10 in regulating the migration and activation of T cells toward sites of sarcoid inflammatory process and the consequent granuloma formation.     

Neurosarcoidosis or Guillain-Barre syndrome complicating sarcoidosis

We described a young male with severe Guillain-Barré syndrome in whom pulmonary sarcoidosis was also detected. Based upon the results of diagnostic procedures (nerve biopsy, CSF examination, electrophysiological study) we postulate that this was a Guillain-Barré syndrome coexisting with sarcoidosis, and not the case of sarcoid neuropathy.     

Selection of T lymphocytes bearing limited TCR-Vbeta regions in the lung of hypersensitivity pneumonitis and sarcoidosis

Hypersensitivity pneumonitis (HP) and sarcoidosis are interstitial lung disorders (ILD) characterized by a lymphocytic alveolitis that, in the active phase of the disease, is sustained by different T-cell subsets, i.e., CD8+ cells in HP and CD4+ lymphocytes in sarcoid patients. To address the question of whether a bias in T-cell selection occurs in the lung of patients with HP and sarcoidosis, we analyzed the T-cell receptor beta chain variable region (TCR-Vbeta) repertoire by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 14 HP and 25 sarcoid patients. To verify whether these cells can be activated in vitro through the TCR, blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins, including SEA, SEB, SEC1, SEC2, SED, and SEE. Flow cytometry and PCR analyses demonstrated an overexpression of cells bearing Vbeta2, Vbeta3, Vbeta5, Vbeta6, and Vbeta8 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments were overrepresented in the lung rather than in the blood. Both in HP and sarcoid patients almost all T cells bearing the dominant Vbeta segment belonged to the T-cell subset that sustains the alveolitis, i.e., CD8 in HP patients and CD4 in sarcoid subjects. Follow-up studies demonstrated that the recovery of the alveolitis was characterized by the disappearance of cells bearing a limited T-cell repertoire. Interestingly, T-lymphocyte response to different superantigens demonstrated that the proliferation elicited by different staphylococcal toxins was more pronounced in the lung than in the blood. Taken together, our findings indicate a compartmentalization of cells bearing discrete Vbeta gene products in the pulmonary microenvironment and suggest that the expansion of specific Vbeta region subsets occurring in the lung might result from triggering by a specific antigen. In fact, the removal from exposure in HP patients or specific treatment in sarcoidosis resulted in the decrease of the overrepresented cell population accounting for the lymphocytic alveolitis.     

Pulmonary sarcoidosis

Sarcoidosis involves the bronchi or lung in more than 90 percent of patients. Intrathoracic manifestations are protean, ranging from asymptomatic bilateral hilar lymphadenopathy to chronic, progressive, (ultimately fatal), respiratory insufficiency. The clinical course is highly variable, and optimal management and treatment are controversial. We review the salient radiographic, physiologic, and histopathologic features of pulmonary sarcoidosis and discuss rare intrathoracic complications (e.g., bronchostenosis, mycetomas, nodular sarcoidosis, necrotizing sarcoid angiitis and granulomatosis, pulmonary vascular and pleural involvement). We discuss the chest radiographic staging system and the role of ancillary diagnostic modalities including high resolution thin section computed tomographic scans (HRCT), bronchoalveolar lavage, radionuclide scan, and serum angiotensin enzyme converting enzyme. Indications for therapy and an overview of therapeutic options are outlined.     

Corticosteroid therapy in cardiac sarcoidosis

Corticosteroid treatment of cardiac sarcoidosis is not conclusive, although sarcoid granulomas in the heart may be more responsive to steroid therapy than in other organs. Healing of sarcoidosis lesions in the heart results in fibrosis and sinning of the myocardium, which may lead to aneurysm formation causing congestive heart failure or sudden death. Congestive heart failure is the leading cause of death in patients with cardiac sarcoidosis in Japan. It is reasonable to initiate steroid therapy as soon as the diagnosis of cardiac sarcoidosis is established in order to prevent fibrosis. Early initiation of steroid therapy with conventional treatment for specific cardiac manifestations (antiarrhythmic therapy, pacemaker implantation and heart failure medication) should bring improvement in the left ventricular systolic and diastolic function with prevention from malignant arrhythmias. Systemic disorder represents a contraindication to organ transplantation, but heart transplantation is now a feasible treatment for patients with end-stage cardiac sarcoidosis with congestive heart failure.     

A case of sarcoid reaction associated with papillary thyroid carcinoma

Sarcoid reaction, a granulomatous lesion similar to those seen in sarcoidosis, has been reported to be associated with various disorders. Here we describe a 54-year-old woman, who was diagnosed with sarcoid reaction associated with papillary carcinoma of the thyroid. Her history included total thyroidectomy with radical neck dissection for a papillary carcinoma of the thyroid. She was found to have a right subclavian mass. Dissection of the mass was performed for the diagnosis of metastatic papillary carcinoma to the lymph node, but the pathological examination showed granuloma without caseation as well as metastasis to the lymph node. Polymerase chain reaction (PCR) of the specimen excluded a possibility of Mycobacterium infection. There was no supporting evidence for systemic sarcoidosis in this patient; the patient showed no skin, eye, or lung lesions, or bilateral hilar lymphadenopathy, and she did not show increase in serum gamma-globulin or in plasma angiotensin-converting enzyme (ACE) levels, or increased CD4/CD8 ratio of lymphocytes obtained from bronchoalveolar lavage. These findings suggest that the present case had sarcoid reaction associated with papillary carcinoma. Although sarcoid reaction has been reported to be associated with various malignancies, only five cases, to our knowledge, are reported in the literature, which were associated with papillary carcinoma.     

Primary lung cancer associated with diffuse granulomatous lesions in the pulmonary parenchyma

A 60-year-old man was admitted to our hospital for productive cough. Chest roentgenography and CT scan disclosed a left hilar tumor invading the mediastinum, with mediastinal lymphadenopathy and diffuse micronodular shadows in both lung fields. A biopsied sample of the tumor revealed squamous cell carcinoma, while noncaseating epithelioid cell granulomas were observed in the samples obtained by transbronchial lung biopsy. The granulomas in the pulmonary parenchyma were determined to be sarcoid reactions secondary to lung cancer, since there was no evidence of sarcoidosis. Combination chemotherapy was effective for the tumor, and the granulomas disappeared after completion of the chemotherapy. These findings suggest the presence of a relationship between sarcoid reactions and lung cancer in this case.     

A methodologic issue for ophthalmic telemedicine: image quality and its effect on diagnostic accuracy and confidence

Sarcoid reactions in lymph nodes with or without metastasis from a primary malignant neoplasm are well-known. However, it is extremely rare to find these reactions associated with cutaneous solid tumors; only one such case has appeared in the literature. Here we describe a case of an 83-year-old man with cutaneous squamous cell carcinoma accompanied by sarcoid reactions and metastatic foci in the regional lymph nodes. The possibilities of systemic sarcoidosis and tuberculosis were excluded after extensive examinations specific for these diseases. Some authors regard the sarcoid reaction to be a sign of a good prognosis on the basis of studies of a few patients with solid tumors. In our case, however, the patient died of pulmonary metastasis with pleuritis carcinomatosa shortly after surgery. Systematic analysis of a sufficient number of cases should be carried out to evaluate the clinical significance of this type of reaction.     

Intraspinal epidural sarcoidosis: case report

OBJECTIVE AND IMPORTANCE: A rare case of lumbar intraspinal epidural sarcoidosis is identified. The rarity of this condition and its clinical presentation are stressed. CLINICAL PRESENTATION: A young Caucasian man presented with the progressive onset of cauda equina syndrome as a result of an expanding mass in the lumbar epidural space compromising the lumbar dural tube from L1 to S1. The patient presented with motor, sensory, and sphincteric dysfunction as a result of this large intraspinal epidural mass. No evidence of systemic illness was noted concomitant with the patient's onset of neurological symptomatology. The patient underwent surgical extirpation of a lumbar intraspinal epidural mass, which was identified histopathologically as sarcoid granuloma. The postoperative work-up included the identification of a mediastinal adenopathy, which was subsequently biopsied and confirmed the diagnosis of sarcoid disease. The patient was treated postoperatively with oral prednisone over a 4-month period. At 7 months postoperatively, the patient had regained gainful employment, the results of his neurological examination were normal, and he was pain-free. INTERVENTION: The patient underwent a multilevel bilateral lumbar laminectomy with facet preservation, extending from L1 to S1, allowing for a gross total removal of the epidural mass. Postoperative oral prednisone was administered as adjuvant therapy for the treatment of multisystem sarcoid disease. CONCLUSION: Aggressive surgical management involving the removal of an extensive epidural mass of the lumbar canal, which was diagnosed as sarcoid disease, coupled with the adjuvant use of oral prednisone has resulted in an excellent outcome for the patient. The results of his clinical examination are now normal, and postoperative radiological imaging reveals no evidence of recurrent or residual disease in the lumbar epidural space. In the unusual case of intraspinal epidural sarcoidosis, the surgical resection of accessible intraspinal epidural masses is recommended, as is the use of oral prednisone postoperatively.