Presence Of Epithelioid Granulomas Research Articles

Isolated cervical lymph node sarcoidosis: a diagnostic challenge of a case report

Sarcoidosis is a granulomatous disorder involving multi-systemic organs. Patients invariably have lung involvement but some may have extrapulmonary disease. Rarely, cervical lymphadenopathy is the only sign without mediastinal or pulmonary abnormalities. We report a Malay male who complained of neck swelling exclusively. On imaging, multiple enlarged cervical lymph nodes deep to the sternocleidomastoid muscle were seen. An excision biopsy revealed non-caseating granulomas with epithelioid macrophages. Extensive investigations led to the diagnosis of isolated cervical lymph node sarcoidosis. Sarcoidosis can present as cervical lymphadenopathy alone, without mediastinal or lung disease. The presence of epithelioid granulomas on histopathology warrants the exclusion of other granulomatous diseases. Isolated cervical lymph node sarcoidosis is only diagnosed in the presence of consistent clinical and radiological findings. In this case, close monitoring for systemic sarcoidosis is important as it can manifest later in life.

Upper Gastrointestinal Tract Involvement in Inflammatory Bowel Diseases: Histologic Clues and Pitfalls.

The upper gastrointestinal (UGI) manifestations of inflammatory bowel diseases (IBDs) are frequently obscured by classic ileal and colonic symptoms and are reported to involve only 0.5% to 4% of adult patients. However, because of the improvement of endoscopic techniques and the growing use of esophagogastroduodenososcopy with biopsy, both asymptomatic and clinically significant esophageal, gastric, and duodenal manifestations are increasingly recognized. The UGI involvement in IBD was historically synonymous with Crohn’s disease (CD), but the doctrine of ulcerative colitis (UC) being limited to the colon has been challenged, and UC-related gastroduodenal lesions have been reported. The diagnosis of UGI IBD should ideally rely on a combination of the clinical history, endoscopic picture, and histologic features. Although endoscopic changes such as aphthoid or longitudinal ulcers and bamboo-joint-like pattern are suggestive of CD, histologic evaluation increases the sensitivity of the IBD diagnosis since histologic alterations may be present in endoscopically unremarkable mucosa. Conversely, in many cases, the histologic findings are nonspecific, and the knowledge of clinical history is vital for reaching an accurate diagnosis. The presence of epithelioid granuloma is highly suggestive of CD but is present in a minority of CD cases; thus, pathologists should be aware of how to diagnose UGI IBD in the absence of granulomata. This article reviews the most important clinical, endoscopic, and histologic features of IBD-associated esophagitis, gastritis, and duodenitis, as well as the IBD-related manifestations in the biliary tract and the postcolectomy setting.

SCROFULA: ANALYZING THE ASPIRATE TO AID IN EARLY DIAGNOSIS

<h3>Background</h3> Tuberculosis is a commonly occurring mycobacterial pulmonary infection that can lead to chronic lymph node enlargement. Scrofula is cervical lymphadenopathy due to tuberculosis. Conventional methods are used to detect the active pulmonary component of the disease. However, tuberculous lymphadenopathy is often difficult to establish routinely; hence, fine-needle aspiration cytology (FNAC) can prove to be a useful aid in diagnosing tuberculous lymphadenopathy. <h3>Objective</h3> To analyze cytomorphological patterns of tuberculous lymphadenopathy by using FNAC and to analyze the presence of acid-fast bacilli (AFB) in different patterns of tuberculous lymphadenopathy by using Ziehl-Neelsen staining. <h3>Methods</h3> One hundred cases of cytologically proven cases of tuberculous lymphadenitis were analyzed, first using Giemsa staining to evaluate and categorize the cytomorphological patterns, then using Ziehl-Neelsen staining to screen of AFB in lymph node aspirate. <h3>Results</h3> Four cytomorphological patterns were seen, which were described as type 1 (primary), presence of neutrophils and suppuration (15%); type 2 (secondary), presence of necrosis, scattered lymphocytes, and degenerated cells (46%); type 3 (tertiary), presence of necrosis, epithelioid cells, and lymphocytes (30%); and type 4 (quaternary), presence of epithelioid granuloma, necrosis, with or without giant cells. AFB positivity was seen in 76% of cases: type 1 (10%), type 2 (39%), type 3 (25%), and type 4 (2%). <h3>Conclusions</h3> FNAC is a quick and economical aid in clinical diagnosis for lymphadenopathies. The cytomorphological pattern for tuberculous lymphadenopathy in the initial phases of the disease shows a reactive response; hence, in cases of suspicion, it is highly advisable for detecting AFB in order to diagnose the cervical lymphadenopathy as scrofula.

Histology and Immunohistochemistry Localization of ESAT6 Expression on Caseous and Non-caseous Granuloma of Extrapulmonary Tuberculosis

Background: TB diagnosis by histopathological examination is based on the presence of epithelioid granuloma with caseous necrosis. The absence of caseous necrosis will make it difficult to distinguish between TB and non-TB granulomas. The use of ESAT-6 as a confirmative examination of TB immunohistochemically has not been fully used nor are there sufficient data showing the features of ESAT-6 immunolocalization in a granuloma. The purpose of the study was to identify differences in ESAT-6 expression in caseous and noncaseous EPTB granulomas.Methods: A cross sectional study using 66 samples of formalin fixed paraffin embedded tissues from several anatomical lesions.The samples previously diagnosed as tuberculous granuloma were evaluated histologically and immunohistochemically. Mann Whitney tests were used for statistical analysis. Result: There were no significant differences in histological findings and immunohistochemical staining of ESAT-6 on macrophages of caseous and non-caseous granuloma of EPTB. ESAT-6 protein was expressed on cytoplasm of epithelioid macrophages, foamy macrophages, Langhans type giant cells and some necrosis areas in the granulomas.Conclusions: This study showed that macrophages of caseous and non-caseous granuloma of EPTB expressed ESAT-6 protein in the same way. This finding supports the use of the anti ESAT-6 antibody as a complementary diagnostic test in diagnosing granuloma of EPTB.

Parathyroid gland hyperplasia associated with tuberculous granulomatous inflammation manifesting as primary hyperparathyroidism

ObjectivesInflammatory disorders of the parathyroid gland are poorly defined. Only seven cases of granulomatous infection have been reported in the literature. Patients and methodsA 68-year-old woman presented with parathyroid hormone level at 277pg/mL and calcium level at 10.8mg/dL, considered as primary hyperparathyroidism. Parathyroidectomy was performed, normalizing analytical values. ResultsNormal-size gland with chief cell hyperplasia, focal pseudofollicular changes, and presence of epithelioid granulomas with Langhans giant cells and caseous necrosis areas, and a positive PCR for M. tuberculosis complex was identified. Chronic granulomatous inflammation could provoke a cascade of immune system activation, resulting in hyperplasia with the consequent increase in parathyroid function, and therefore primary hyperparathyroidism. ConclusionsIn populations with a high incidence of tuberculosis, the coexistence of these pathologies must be kept in mind. This theory needs further biomolecular studies to be confirmed, but it provides a new perspective within the possible etiologies of hyperparathyroidism.

Comparative pathologic analysis of mediastinal B-cell lymphomas: selective expression of p63 but no GATA3 optimally differentiates primary mediastinal large B-cell lymphoma from classic Hodgkin lymphoma

BackgroundInterpretation of mediastinal biopsy is often challenging even for experienced pathologists especially when a hematolymphoid neoplasm is suspected. Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphomas of the mediastinum. Although PMLBCL and mediastinal CHL share many clinicopathologic characteristics, their treatment strategies and responses are remarkably different. We therefore aimed to find distinctive histologic or protein markers to better differentiate these two lesions.MethodsSearch for primary mediastinal B-cell lymphomas found 52 consecutive cases from 3 university hospitals of Korea during 2005 to 2012. Among them, 32 cases that were available for additional immunohistochemistry (IHC) assessment were enrolled in this study. These cases consisted of the following: CHL (N = 13), PMLBCL (N = 16), and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (gray zone lymphoma, N = 3). Along with the clinicopathologic findings, the expression of p63, GATA3 and cyclin E was investigated by IHC in the three categorized lesions mentioned above.ResultsMost clinical features overlapped between PMLBCL and CHL except for the increased disease progression and mortality found in PMLBCL. In the pathologic review, the presence of epithelioid granuloma favored a diagnosis of CHL, whereas reticulated or alveolar patterns of fibrosis were characteristic of PMLBCL. For protein markers, p63 was predominantly positive in PMLBCL (15/16) compared with CHL (2/13), which indicates that p63 is a marker of the highest diagnostic accuracy when calculated by the area under the ROC curve. GATA3 was expressed in the majority of CHL cases (10/13) compared with PMLBCL (0/16), while the expression of cyclin E was only rarely present in a minor population of PMLBCL.ConclusionsP63 expression in tumor cells, even focal expression, and no GATA3 is the most helpful feature in distinguishing PMLBCL from mediastinal CHL.

Enfermedad granulomatosa hepática.

Granulomas are circumscribed lesions mainly composed of mononuclear cells that arise in response to poorly degradable antigenic stimuli. They are found in 2-15 % of liver biopsies and the meaning of their finding can range from an incidental phenomenon to the manifestation of a systemic disease of infectious, autoimmune or neoplastic origin. Clinical presentation usually points at the underlying pathology; however, the list of associated conditions is extensive, and differs based on patient epidemiological history and baseline characteristics. The most useful element for their study is a thorough medical history, with an emphasis on recent trips, exposures and consumption of drugs or raw or exotic foods. Detailed histopathological analysis may help identify the etiology. For example, the presence of epithelioid granulomas with caseous necrosis indicates tuberculosis and, its absence, sarcoidosis; eosinophil abundance can be associated with drug reactions or parasitic infections; and the presence of foreign bodies can be the cause of granulomatous liver disease (GLD). In this article, we describe the basic clinical-pathological aspects of GLD, and provide a brief summary of the most common etiologies, with an emphasis on the Latin-American region.

Crohn's disease of esophagus, stomach and duodenum.

Crohn’s disease with involvement of the esophagus, stomach and duodenum has a prevalence of 0.5% to 4% in symptomatic adult patients, but some studies have shown that these results may be underestimated, since upper gastrointestinal endoscopy is not performed routinely in the initial evaluation of the disease in adult patients, as it is in the pediatric population. In general, involvement of the upper gastrointestinal tract in Crohn’s disease occurs concomitantly with involvement of the lower gastrointestinal tract. The diagnosis depends on clinical, endoscopic, histological and radiological evaluation. The presence of aphthoid ulcers, longitudinal ulcers, bamboo-joint-like appearance, stenoses and fistulas are endoscopic findings suggestive of the disease, and it is important to exclude the presence of Helicobacter pylori infection. The primary histological findings, which facilitate the diagnosis, are the presence of a chronic inflammatory process with a predominance of lymphoplasmacytic cells and active focal gastritis. The presence of epithelioid granuloma, although less frequent, is highly suggestive of the disease in the absence of chronic granulomatous disease. Treatment should include the use of proton pump inhibitors associated with corticosteroids, immunomodulators and biological therapy according to the severity of the disease.

DC-SIGN and VDR polymorphisms are associated with chronic form of paracoccidioidomycosis with oral manifestations.

Paracoccidioidomycosis (PCM) is a granulomatous disease caused by fungi of the species complex of the Paracoccidioides genus. One of the main clinical manifestations of PCM is the presence of oral lesions with the presence of epithelioid granulomas. In this work, we aimed to evaluate the frequency of SNPs in the TNF-α, JAK1, VDR, DC-SIGN and FcγRIIa genes in patients with chronic PCM and verify possible association of these SNPs with the organisation pattern of the granulomas in the oral lesions. A total of 66 samples of DNA were obtained from oral lesions biopsies and 106 DNA samples were obtained from healthy individuals. The individuals were genotyped for SNPs in DC-SIGN (rs4804803), FcγRIIa (rs1801274), JAK1 (rs11208534), TNF-α (rs1800629) and VDR (rs7975232) by real-time PCR and allele discrimination method. Granulomas were classified as loose or dense according to the histological pattern. In the VDR (rs7975232), the CC genotype (P<0.001, OR=5.94, 95% CI=2.07-17.05), and the C allele (P=0.027, OR=2.71, 95% CI=1.07-6.86), as well as the GG genotype in DC-SIGN (rs4804803) (P=0.032, OR: 3.76, 95%, I=1.06-13.38) are associated with an increased risk of oral PCM. Our data indicate that VDR and DC-SIGN genetics variations are related to the susceptibility of oral PCM in the group of patients analysed.

Unusual presentation of a skull base mass lesion in sarcoidosis mimicking malignant neoplasm: a case report

BackgroundSarcoidosis is a multi-organ disease of unknown etiology characterised by the presence of epithelioid granulomas, without caseous necrosis. Systemic sarcoidosis is rare among children, while neurosarcoidosis in children is even rarer whether it is systemic or not.Case presentationWe described the case of a 12-year-old boy who presented with monocular vision loss accompanied by unusual MRI features of an extensive meningeal infiltrating mass lesion. The patient underwent surgical resection (biopsy) via a frontotemporal craniotomy to establish a definitive diagnosis based on the histopathology, since neurosarcoidosis remains a very difficult diagnosis to establish from neuroradiogenic imagings. Based on the histopathology of the resected mass lesion, neurosarcoidosis was diagnosed. On follow-up after 3 months of steroid therapy, the patient displayed a good response on the imaging studies. MRI revealed that the preexisting mass lesion had regressed extremely. We also conducted a small literature review on imaging studies, manifestations, appropriate treatments, etc., in particular neurosarcoidosis including children.ConclusionAlthough extremely rare, neurosarcoidosis, even in children, should be considered in the differential diagnosis of skull base mass lesions to avoid unnecessary aggressive surgery and delay in treatment, since surgery may have little role in the treatment of sarcoidosis.

Pathological and computed tomography findings of lymphoepithelioma-like gastric carcinoma with epithelioid granulomas: A case report

Lymphoepithelioma-like carcinoma is a distinct entity among Epstein-Barr virus (EBV)-associated gastric carcinomas, characterized by the presence of a lymphoid stroma with small nests of cancer cells uniformly distributed throughout. Epithelioid granulomas with multinucleated giant cells are extremely rare in the tumor tissue. The presence of epithelioid granulomas with prominent lymphocyte infiltration is associated with a favorable prognosis. This lesion tends to form a bulging mass in the submucosa. In the present study, we report a lymphoepithelioma-like carcinoma of the stomach with epithelioid granulomas which appeared as a bulging mass in CT scanning and correlate it with the pathology. Clinicians and radiologists should recognize the features of such tumors.

Experimental epithelioid cell granuloma formation in Lewis rats induced by injection of cell wall fragments derived from alpha-streptococcus--etiologic relationship between bacterial cell wall and sarcoid granuloma

We observed the presence of epithelioid granulomas in follicles near lacunae in the tonsils from patients with active sarcoidosis. Bacteria isolated in these tissues were mostly alpha-streptococci. The present study was undertaken to determine whether alpha-streptococcus can induce granuloma formation. Streptococcal cell wall (SCW) fragments were injected into the foot pads of female Lewis rats. Epithelioid granulomas were abundantly formed in popliteal lymph nodes when SCW aqueous suspension was injected four times. SCW antigens were detected in macrophages in the granuloma but not in epithelioid cells, by immunoperoxidase method. These findings suggest that macrophages transform into epithelioid cells after phagocytosis and digestion of SCW, and that components of bacterial cell wall such as SCW may induce the granuloma formation in sarcoidosis.

Primary Tubercular Osteomyelitis Of The Sternum: Report of Two cases

Tubercular involvement of the sternum, leading to osteomyelitis, is a rarely described entity even in countries where tuberculosis is endemic. Frank Presentation of this entity is even more uncommon. We describe two cases who presented with discharging sinuses with erythematous lesion over the sternum with constitutional symptoms like fever, loss of appetite and significant weight loss, but without features of pulmonary tuberculosis like cough, hemoptysis. Plain Radiographs demonstrated eroding cortex of the manubrium with lytic lesion. Tubercular etiology was suggested by presence of epithelioid granulomas and acid fast bacilli in the Ziehl-Neelsen staining of the aspirate from the lesion. Both patients responded well to antitubercular treatment.

Pathology of Naturally Occurring Paratuberculosis in Water Buffaloes (Bubalus bubalis)

Gross and histologic lesions of paratuberculosis were studied in water buffaloes. Small intestines and associated mesenteric lymph nodes of 405 water buffaloes were examined. Of these, 20 animals having visible changes of intestinal thickening, mucosal corrugations, and enlargement of mesenteric lymph nodes exhibited histologic alteration characteristics of mild to moderate granulomatous inflammation. The histologic lesions observed in these animals were classified into 3 grades on the basis of type of cellular infiltration, granuloma formation, and presence of acid-fast bacilli. Grade-1 lesions observed in 8 animals were marked by the presence of scattered epithelioid macrophages amid large number of lymphocytes in the intestinal villi and in the paracortical regions of the associated mesenteric lymph nodes. Another 8 animals classified under grade-2 revealed microgranulomas, infiltration with a larger number of epithelioid macrophages besides lymphocytes in the intestinal villi, and granulomas in the mesenteric lymph nodes. Grade-3 lesions observed in 4 animals were characterized by the presence of epithelioid granulomas and giant cells in the intestines and the mesenteric lymph nodes. The Ziehl-Neelsen's stained tissue sections revealed acid-fast bacilli in grade-3 and -2 animals and acid-fast granular debris in grade-1 animals. Among these 20 buffaloes, 14 (70%) were positive in the IS900 specific polymerase chain reaction and 6 (30%) were positive in the bacterial culture.

Primary tubercular osteomyelitis of the sternum

Tubercular involvement of the sternum, leading to osteomyelitis, is a rarely described entity even in countries where tuberculosis is endemic. Presentation in pediatric age group is even more uncommon. We describe a 12 year old girl who presented with a mass over the manubruim sterni and fever. CT chest demonstrated a soft tissue mass in the anterior mediastinum, eroding the cortex of the manubrium. Tubercular etiology was suggested by presence of epithelioid granulomas and acid fast bacilli in the Ziehl-Neelsen staining of the aspirate from the lesion. The patient responded well to antitubercular treatment.

The presence of epithelioid granulomas in hepatitis C virus-related cirrhosis

We examined surgical liver specimens from 52 patients with hepatitis C virus-related cirrhosis. All patients underwent orthotopic liver transplantation at Paul Brousse Hospital. They were found to be seropositive for antibodies to hepatitis C virus by second-generation testing (RIBA 2, Ortho Diagnostic Systems Inc, Westwood, MA). We detected multiple granulomas in five (10%) of the cirrhotic livers. These granulomas were composed of epithelioid cells, sometimes associated with multinucleated giant cells, and were surrounded by small lymphocytes and fibrosis. The epithelioid granulomas were located within the cirrhotic nodules. They were not present within the portal tracts or within the fibrosis. These granulomas were diffusely distributed in the liver. None of the patients with diffuse hepatic epithelioid granulomas had evidence of tuberculosis or brucellosis before transplantation or during the follow-up period (range, 3 to 20 months). They had no detectable cause of granulomatous hepatitis. The role of hepatitis C virus as a cause of epithelioid granulomas is discussed.

Correlation of presence of granulomas with clinical and immunologic variables in Crohn's disease.

Approximately 50% of patients with Crohn's disease have epithelioid granulomas present in the diseased intestine. Some studies have associated the presence of granulomas with a good prognosis. In this prospective study, 44 patients with Crohn's disease requiring surgery were followed up for five years. Twenty-two patients (50%) had granulomas. Patients with granulomas were younger and had a shorter duration of disease. They also had more extensive disease and a greater degree of peripheral lymphopenia. Follow-up showed a trend toward greater recurrence rate in the patients with granulomas. It seems that patients with aggressive and extensive Crohn's disease are not protected from the development of symptomatic early recurrence by the presence of epithelioid granulomas.

Epithelioid Granulomas in Hodgkin Disease

Histologic sections of spleen and liver prepared from tissue obtained during exploratory laparotomy and splenectomy in 91 untreated patients with Hodgkin disease were reviewed to assess the incidence and possible implications of noncaseating, epitheliod, sarcoid-like granulomas. The 17 patients with granulomas and the 74 patients without granulomas did not differ appreciably with respect to pretreatment indexes. All patients were observed for at least 15 months following laparotomy or until the time of death (range, 15 to 67 months; median, 25 months). The 17 patients with granulomas tended to have fewer relapses, longer survival, and lower incidence of subsequent herpes zoster infection compared to the 74 without granulomas. The presence of epithelioid granulomas in association with Hodgkin disease may reflect a host response to the tumor with favorable prognostic implications.

Epithelioid granulomas in Hodgkin disease. A favorable prognostic sign?

Histologic sections of spleen and liver prepared from tissue obtained during exploratory laparotomy and splenectomy in 91 untreated patients with Hodgkin disease were reviewed to assess the incidence and possible implications of noncaseating, epithelioid, sarcoid-like granulomas. The 17 patients with granulomas and the 74 patients without granulomas did not differ appreciably with respect to pretreatment indexes. All patients were observed for at least 15 months following laparotomy or until the time of death (range, 15 to 67 months; median, 26 months). The 17 patients with granulomas tended to have fewer relapses, longer survival, and lower incidence of subsequent herpes zoster infection compared to the 74 without granulomas. The presence of epithelioid granulomas in association with Hodgkin disease may reflect a host response to the tumor with favorable prognostic implications. (<i>JAMA</i>233:886-889, 1975)