Sarcoid-like Lesions Research Articles

Cathepsin K – a marker of macrophage differentiation?

Cathepsin K is a cysteine protease with high matrix-degrading activity. Initially, cathepsin K was described as being expressed exclusively by osteoclasts. It was suggested that cathepsin K expression is a specific feature of cells involved in bone remodelling. The aim of this study was to investigate the hypothesis that cathepsin K is expressed not only in bone-resorbing macrophages, but also more generally in specifically differentiated macrophages, such as epithelioid cells and multinucleated giant cells in soft tissues. Specimens obtained from different organs and anatomical locations of patients suffering from sarcoidosis, tuberculosis, granulomas caused by foreign materials, and sarcoid-like lesions were investigated for the expression of cathepsins B, K, and L. Immunohistochemistry and in situ hybridization showed cathepsin K in epithelioid cells and multinucleated giant cells irrespective of the pathological condition and anatomical location, but not in normal resident macrophages. By immunoelectron microscopy, cathepsin K was discovered in cytoplasmic granules of multinucleated giant cells. In contrast, cathepsin B and cathepsin L were expressed ubiquitously in CD68-positive tissue macrophages, epithelioid cells, and multinucleated giant cells. The results demonstrate that cathepsin K, but not cathepsin B or cathepsin L, differentiates specific phenotypes of macrophages independently of the anatomical site. Its enzymatic characteristics, particularly its high matrix-degrading activity, suggest that cathepsin K-positive epithelioid cells and multinucleated giant cells are characterized by an enhanced specific proteolytic capability. Copyright © 2001 John Wiley & Sons, Ltd.

Cathepsin K--a marker of macrophage differentiation?

Cathepsin K is a cysteine protease with high matrix-degrading activity. Initially, cathepsin K was described as being expressed exclusively by osteoclasts. It was suggested that cathepsin K expression is a specific feature of cells involved in bone remodelling. The aim of this study was to investigate the hypothesis that cathepsin K is expressed not only in bone-resorbing macrophages, but also more generally in specifically differentiated macrophages, such as epithelioid cells and multinucleated giant cells in soft tissues. Specimens obtained from different organs and anatomical locations of patients suffering from sarcoidosis, tuberculosis, granulomas caused by foreign materials, and sarcoid-like lesions were investigated for the expression of cathepsins B, K, and L. Immunohistochemistry and in situ hybridization showed cathepsin K in epithelioid cells and multinucleated giant cells irrespective of the pathological condition and anatomical location, but not in normal resident macrophages. By immunoelectron microscopy, cathepsin K was discovered in cytoplasmic granules of multinucleated giant cells. In contrast, cathepsin B and cathepsin L were expressed ubiquitously in CD68-positive tissue macrophages, epithelioid cells, and multinucleated giant cells. The results demonstrate that cathepsin K, but not cathepsin B or cathepsin L, differentiates specific phenotypes of macrophages independently of the anatomical site. Its enzymatic characteristics, particularly its high matrix-degrading activity, suggest that cathepsin K-positive epithelioid cells and multinucleated giant cells are characterized by an enhanced specific proteolytic capability.

Incidence and prognostic significance of epithelioid cell reactions and microcarcinoses in regional lymph nodes in stomach carcinoma

The frequency and prognostic relevance of sarcoid-like lesions and microcarcinosis in regional lymph nodes in gastric cancer (n = 113; pT1-3, pN0-1, pM0, R0) were investigated; the prognostic value was compared with pT and pN stage, grading and Laurén's tumor classification with Cox's multivariate regression-model. Sarcoid like lesions were found in 34% of the cases (n = 113). Statistical analysis did not indicate that they had any prognostic value or showed whether or not microcarcinosis or metastasis was present; they were independent of pT stage, histological tumor type, tumor grading, and the clinical course of disease. Microcarcinosis (defined as scattered carcinoma cells within lymph node sinuses or pulp without adjacent stromal reaction) was revealed by immunohistochemistry in 90% of pN0 cases; the presence of 3 or more tumor cells per lymph node section in over 10% of sampled lymph nodes per case carried a significant prognostic value. In microcarcinosis without evidence of metastasis, the number of tumor cells and the number of involved lymph nodes are of prognostic value. In pN1 cases microcarcinosis was found as well as the metastases in 97% and had no additional prognostic value. Microcarcinosis alone has a different significance from lymph node metastasis for prognosis.

Diagnosis and Management of Urethral Sarcoidosis

We report on a woman with urethral sarcoidosis with obstructive urinary symptoms and previously known systemic sarcoidosis. The diagnosis of this rare lesion and management are discussed, and the genitourinary manifestations of sarcoidosis are reviewed.

Sarcoidlike granulomas as an early manifestation of Whipple's disease

Whipple's disease is often accompanied by a long, preintestinal phase of vague symptoms, such as weight loss, fever, and migratory arthralgia, which may delay diagnosis and proper treatment. We report a patient who presented with sarcoidlike granulomas in the lung 1.5 yr before the development of gastrointestinal symptoms. He was treated with prednisone and his lung lesions improved dramatically. However, steroids could not be discontinued until the diagnosis of Whipple's disease was made and he was started on antibiotic treatment. Whippie's disease was diagnosed from a small intestinal biopsy specimen by electron microscopic demonstration of characteristic bacillary bodies. Liver biopsy specimens also demonstrated a few Kupffer cells containing degenerative bacillary bodies. Based on this case and other reported cases of Whipple's disease with sarcoidlike lesions in various organs, we suggest that sarcoidlike tissue reaction can be an early manifestation of Whipple's disease, recognition of which may have practical value in facilitating an early diagnosis and treatment.

Lymph node reactions to cancer.

Histological, histomorphometrical and histochemical data on the response of regional lymph nodes to tumor development, as recorded in experimental and clinical studies, were coordinated and supplemented by recent findings in experimentally induced autochthonous carcinomas in the rat gastrointestinal tract. The attempted correlation led to the definition of several prognostic parameters: 1) The development of germinal centers and the plasmocytic reaction in tumor draining nodes are morphological expressions of active humoral immune responses that may be specifically directed against the tumor. These reactions attain their maximum usually during late stages of tumor development. Their incidence and prognostic significance may vary depending upon the stage and the type of tumor. 2) Sinus histiocytosis is an immunologically nonspecific lymph node response with debatable prognostic significance. 3) Granulomatous sarcoid-like lesions may be understood as signs of an immunologically mediated antitumor response of macrophages activated by T lymphocytes. They are indicative of a favorable prognosis. 4) Paracortical hyperplasia, characterized by an increased population of lymphocytes and eventually immunoblasts, is an expression of an active T-cell reaction. This reaction occurs typically during early stages of experimental tumors. Correspondingly, it is of favorable prognostic significance in human tumors. 5) Lymphocytic depletion and nodular alteration of T-cell areas, with increased histiocytic infiltration, are reactions most often seen in the draining nodes of an advanced tumor. Both seem to coincide with depression of the cell-mediated immune reactivity. The present assessment of the reactive behavior of diverse lymph node compartments may serve as a first pointer to the proposed histologic immunostaging of malignant tumors.

'Sarcoidosis' and Sarcoid-like Lesions

• Mediastinal, paratracheal, and hilar adenopathy developed in two patients during or shortly after adjunctive cytotoxic or radiation therapy for nonseminomatous testis cancer. Lymph nodes obtained by mediastinoscopy contained multiple noncaseating granulomas with no histologic evidence of testis cancer. A Kveim test in one patient was positive. These patients were believed to have sarcoidosis with mediastinal lymphadenopathy that resolved without specific therapy. The temporal relationship between the administration of antineoplastic therapy and the development of granulomatous mediastinal adenopathy in these two patients and in one patient previously described suggests a relationship between such therapy and sarcoidosis. (Arch Intern Med141:37-38, 1981)

Epithelioid cell granulomata in the mucosa of the small intestine in Whipple's disease

This report is the first description of sarcoid-like epithelioid cell granulomata in the mucosa of the small intestine in a case of Whipple's disease. The epithelioid cells do not contain PAS-positive material or products of bacterial degradation. Their ultrastructural features characterize them as histiocytes which have become secretory rather than phagocytic. These sarcoid-like lesions are considered to be a morphological manifestation of an immunological process in Whipple's disease and not to represent evidence of sarcoidosis as a concomitant or associated disorder.

Morphology and therapeutic chances of interstitial lung disease.

101 cases of idiopathic interstitial lung disease diagnosed by lung biopsy, were reviewed according to clinical and X-ray appearance and especially to their response to steroid therapy. Four morphological inflammatory reactions are distinguished: (1) alveolitis; (2) onion-like mesenchymal proliferation; (3) sarcoid-like lesions, and (4) lymphofollicular reactions. Especially type 1 and/or type 2 show immediate response to steroid therapy. Only a few cases showed spontaneous improvement. Once a fibrosis exists, a 'restitutio ad integrum' cannot be expected any where. From this group of idiopathic interstitial lung diseases the conclusion seems to be justified that also other types of interstitial lung reactions should be treated with steroids to avoid it turning into lung fibrosis.

Sarcoid-Like Lesions in the Lung by Selective Intrabronchial Instillation of Antigen in Previously Sensitized Rabbits

Sarcoid-like lesions were observed in the lung after selective intrabronchial instillation of antigen in previously sensitized rabbits. These lesions consisted of an early exudative phase, an intermediate phase of interstitial pneumonia and a late proliferative phase. Sarcoid-like granulomas, similar to granuloma, in human lung developed during the late phase.

Tuberculoid granulomata in regional lymph nodes of malignant cutaneous melanoma.

In the surgical specimen of a unilateral complete neck dissection by cervicallymph nodes in malignant cutaneous melanoma in the neck, histological examination and later complementary research made possible a diagnosis of <i>paraneoplastic tuberculoid granulomata (‘sarcoid-like lesions’) in regional lymph nodes</i>.

Sarcoid-like lesions (epithelioid cell granulomatosis) of regional lymph nodes in association with carcinoma of the cervix.

Sarcoid-like lesions (epithelioid cell granulomatosis) of regional lymph nodes in association with carcinoma of the cervix.

SCALENE NODE "SARCOIDOSIS": BENIGN OR MALIGNANT?

Biopsy of the scalene lymph nodes is frequently done inan attempt to diagnose pulmonary disease. 1 While this procedure is often rewarding, uncritical acceptance of a diagnosis based on such a biopsy can lead to error. The case reported here, a patient with pulmonary carcinoma in whom the histology of the scalene lymph node was compatible with sarcoid, illustrates this hazard. We would like to emphasize in this report that sarcoid-like lesions occur in scalene lymph nodes in association with lung carcinomas, and the clinician who is unaware of this association may fail to diagnose an underlying malignancy. Report of Case A 48-year-old Negro female was admitted to Detroit Receiving Hospital on Jan 11, 1962, with a chief complaint of loss of appetite of five weeks' duration. She had lost 27 pounds in five weeks. She developed shortness of breath and wheezing four weeks prior to admission. She denied cough,

The significance of sarcoid-like lesions in association with malignant neoplasms

1. 1. The literature concerning Boeck's sarcoid and sarcoid-like lesions in association with malignant neoplasms is reviewed. 2. 2. Three cases illustrating the association of sarcoid-like lesions in the regional lymphatics draining a primary malignant neoplasm of the lung are presented. 3. 3. The association may occur more often than is generally appreciated or reported. 4. 4. Regional lymph nodes draining a primary malignant tumor site may at times contain sarcoid-like lesions. Failure to recognize this fact may lead to failure of diagnosis of an underlying malignant neoplasm. 5. 5. Awareness of this complex is especially important in view of the frequent use of scalene lymph node biopsy in the evaluation of intrathoracic disorders. It is likewise important when lymph node biopsy is performed at other sites for diagnostic purposes.

The co-existence of bronchial carcinoma and sarcoidosis

Summary A case of bronchial carcinoma with co-existent sarcoidosis is presented. The significance of sarcoid-like lesions in association with malignant disease and in the glands draining the malignant areas is discussed, with reference to similar changes observed in association with chronic inflammatory and granulomatous lesions.

Histoplasmosis; three fatal cases with disseminated sarcoid-like lesions.

THE THREE fatal cases of histoplasmosis with disseminated sarcoid-like lesions which are reported in this paper serve as evidence for the view that subacute or chronic histoplasmosis may, in some instances, exhibit certain clinical and pathologic features often regarded as diagnostic of sarcoidosis. In recent years it has become clear that the clinical manifestations evoked by Histoplasma capsulatum are as protean as those of tuberculosis. Histoplasmosis may be localized or generalized; often it is localized for months or years, eventually becoming generalized. It may be acute, subacute, recurrent, or chronic, and it may be severe, mild, or completely asymptomatic. 1 Almost any organ or tissue may be involved, but lesions are most frequently seen in the lungs, lymph nodes, spleen, liver, intestine, adrenal glands, bone marrow, skin, and naso-oral cavity. The lesions of histoplasmosis are almost as varied as the clinical picture. They show every gradation of granulomatous reaction from

Pathological and experimental studies of Boeck's sarcoid; report of a case with panarteritis, periarteritis, terminal-hypertension and uremia, and the reproduction of a sarcoid-like lesion in guinea pigs.

Pathological and experimental studies of Boeck's sarcoid; report of a case with panarteritis, periarteritis, terminal-hypertension and uremia, and the reproduction of a sarcoid-like lesion in guinea pigs.

The Osseous Lesions of Sarcoidosis

In the fifty years which have passed since Caesar Boeck (1) first described an apparently rare dermatologic condition which he chose to call “multiple benign sarkoid of the skin,” this disease has come to be recognized as a generalized systemic disorder of interest and importance not only to dermatologists but to physicians in virtually all branches of medical practice. On occasion sarcoid lesions apparently confined to the skin are encountered, but the consistency with which deep-seated sarcoidosis occurs with or without skin alterations warrants thorough investigation of all organ-systems of patients in whom the disease is suspected. The evolution of sarcoidosis as we now recognize it has been carefully documented by many writers, notably Hunter (2) and Longcope and Pierson (3). Their accounts of Hutchinson's “Mortimer's malady,” Besnier's lupus pernio, Boeck's multiple benign sarcoid, Heerfordt's uveoparotid fever, Schaumann's lymphogranuloma benignum, Jüngling's osteitis tuberculosa multiplex cystica, and certain instances of the Mikulicz syndrome, and how all these apparently specific diseases were gradually recognized as different manifestations of a single clinicopathologic entity constitute one of the most fascinating chapters in the history of medicine. Nor has the chapter yet ended, for not only do each few years bring reports of sarcoidosis involving portions of the body in which it has not hitherto been described and new tests for the determination of its presence (4, 5), but the etiology of the condition never has been satisfactorily established. Schaumann (6, 7), who made the first real attempt to correlate the various clinical and pathological manifestations of sarcoidosis, insists that the disease is primarily one of the lymphohematopoietic system, with or without involvement of the skin, and that the reporting of lesions in other portions of the body represents a failure to distinguish “what is essential and what is accidental.” Like Besnier (8), Boeck (1), and Jüngling (9), as well as the majority of modern authorities, Schaumann has consistently maintained that sarcoidosis is a peculiar manifestation of tuberculosis. One can find considerable support for this theory in the contributions of various laboratory research workers. For example, Jadassohn (10) has produced sarcoid-like lesions in the skin of rats by injection of tubercle bacilli, and Florence Sabin (11) and her co-workers have obtained non-caseating “hard” tubercles typical of sarcoid by injecting only the lipoid fraction of tubercle bacilli into laboratory animals. On the other hand, it has been found that sarcoid-like lesions can be produced locally by the injection of other organisms (12) as well as by numerous inert substances such as grass (12) and silica (13).