Tuberculosis cutánea esporotricoide en la Amazonía peruana: reporte de caso / Sporotrichoid cutaneous tuberculosis in the peruvian amazon: case report

RESUMEN La tuberculosis cutánea es una presentación rara de la infección por Mycobacterium tuberculosis. Se presenta el caso de una mujer sin antecedentes médicos de importancia, con un tiempo de enfermedad de año y medio, caracterizado por lesiones tipo esporotricoide, con diseminación linfocutánea en miembro superior derecho, de evolución lentamente progresiva. Se realizó un estudio histopatológico encontrándose células gigantes tipo Langhans y escasa necrosis. El paciente recibió terapia de esquema sensible antituberculoso, con evolución favorable.

ABSTRACT Cutaneous tuberculosis is a rare presentation of Mycobacterium tuberculosis infection. We present the case of a woman without important medical history, with a disease period of one year and a half, characterized by sporotrichoid-like lesions, with lymphocutaneous dissemination in the right upper limb, and with slowly progressive evolution. The histopathological tests revealed Langhans type giant cells and scarce necrosis. The patient received therapy with a sensitive antituberculous scheme, and evolved favorably.

Cystic neutrophilic granulomatous mastitis: an update.

Cystic neutrophilic granulomatous mastitis (CNGM) is a rare subtype of granulomatous mastitis with a highly distinct histological pattern often associated with Corynebacterium species. CNGM is characterised by suppurative lipogranulomas that are composed of central lipid vacuoles rimmed by neutrophils and an outer cuff of epithelioid histiocytes. Some of the lipid vacuoles may contain sparse, rod-shaped, gram-positive bacilli that can be easily missed or dismissed. The surrounding mixed inflammatory infiltrate contains Langhans-type giant cells, lymphocytes and neutrophils. CNGM occurs in reproductive age women with a history of pregnancy and typically presents as a palpable mass that can be painful. CNGM has many mimickers, most significantly breast carcinoma. In many cases, CNGM has significant pathological and clinical overlap with other forms of granulomatous mastitis. Given the association with Corynebacterium species, early diagnosis of CNGM is essential in offering patients the most appropriate treatment. Prolonged antibiotic therapy specifically directed to corynebacteria is required, sometimes even beyond resolution of clinical symptoms. This comprehensive review of the existing literature on CNGM describes clinical-pathological features, microbiological findings, challenges associated with the microscopic differential diagnosis, clinical implications of this diagnosis and emerging treatment options. Morphological criteria and suggested comments to convey the degree of diagnostic certainty are also proposed for standard pathology reporting.

Interleukin-22 receptor 1 is expressed in multinucleated giant cells: A study on intestinal tuberculosis and Crohn's disease.

BACKGROUND: It is challenging to distinguish intestinal tuberculosis from Crohn's disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)-23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM: To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS: We analysed 133 patients with intestinal tuberculosis, 128 with Crohn's disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1ß rs1143627, TGFß rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS: The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION: High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.

Low levels of alpha-synuclein in peripheral tissues are related to clinical relapse in relapsing-remitting multiple sclerosis: a pilot cross-sectional study.

The protein alpha-synuclein (α-Syn) has been linked to neuroinflammatory conditions. We investigated whether the presence of α-Syn in peripheral tissues is a surrogate of brain inflammatory status in a small group of relapsing-remitting multiple sclerosis (RRMS) patients in a pilot cross-sectional study. Skin biopsies and peripheral blood were sampled from 34 healthy controls and 23 MS patients for measurement of α-Syn levels. Within the RRMS group 15 patients were in remission, and 8 patients were in the relapsing phase. The protein α-Syn was evaluated by means of immunohistochemistry and flow cytometry in skin and nucleated blood cells, respectively. In the skin, α-Syn levels were lower in relapsing MS than in the other groups, both in positive area (p = .021) and staining intensity (p = .004). In blood, the percentage of α-Syn-positive lymphocytes and monocytes were not statistically different between study groups. Moreover, the use of systemic steroids did not affect α-Syn positivity in MS-relapse patients. Finally, epidermic Langerhans cells did not stain positively for α-Syn. Overall, the levels of α-Syn positivity were lower in inflammatory relapse of RRMS patients when measured in peripheral tissues. We discuss the role of α-Syn levels in inflammation according to the obtained results.

Tuberculosis of the Cheek: A Rare Presentation.

Tuberculosis (TB) typically attacks the lungs. The oral lesions either primary or secondary are rarely seen and often overlooked by the clinician. More so, their atypical presentations make the diagnosis challenging; especially when they are present before the systemic symptoms become apparent. We report a case of primary tuberculosis in a 4 year old female child in a very uncommon location, the cheek. The timely diagnosis and antitubercular therapy resulted in complete resolution of the swelling within 6 months.

Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection.

Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.

Abdominal tuberculosis: utility of laparoscopy in the correct diagnosis.

INTRODUCTION: Abdominal tuberculosis is one of the most prevalent form of extra-pulmonary disease, and the diagnosis is difficult because of non-specific clinical features. METHOD: We presented a case of a Tunisian woman with cough, nausea, decreased appetite and pelvic-abdominal pain. CT scan showed peritoneal thickening, peritoneal tiny nodules and enlarged mesenteric lymph nodes ascitic fluid. Sputum analysis was negative. Abdominal paracentesis was performed, and no malignant cell was detected. The Ziehl staining revealed a negativity for acid-fast bacilli. RESULTS: Diagnostic laparoscopy was performed. Biopsy specimens of peritoneum, liver, omentum and diaphragm showed omental epithelioid granulomas with a centrale caseous necrosis and Langhans giant cells. The patient received anti-tubercular treatment. CONCLUSIONS: In case of suspicion of tuberculosis, when bacteriologic and cytologic analysis is negative, laparoscopy with biopsies is helpful for correct diagnosis and appropriate management.

The T-SPOT.TB Test for Diagnosis of Breast Tuberculosis.

OBJECTIVE: To assess the diagnostic value of the T-SPOT.TB test in cases of breast turberculosis (BTB) in China. METHODS: We enrolled 13 female patients with primary BTB as the BTB test group and 10 healthy volunteers as the control group. The 2 groups underwent T-SPOT.TB tests and tuberculin skin tests (TSTs) before receiving a core-needle biopsy or excision biopsy. We then collected and analyzed T-SPOT.TB and TST data. RESULTS: The sensitivity of the T-SPOT.TB test for detection of BTB (84.6%) was significantly greater than that of TST (53.8%) (P <.05); the specificity of each test (80.0% and 60.0%, respectively) for BTB was not significantly different (P >.05). CONCLUSION: The T-SPOT.TB test could be a useful adjunct to current tests for diagnosis of BTB and could be used for early diagnosis of this condition.

Tuberculosis of the entheses.

PURPOSE: Tuberculosis of the osteoarticular system usually manifests as joint arthritis. There is no available English literature on the tubercular involvement of the enthesis (tendon-bone junction). METHODS: We performed a retrospective analysis on 14 patients with tuberculosis of the tendon-bone junction. Patients presenting with a sinus with or without presence of radiological evidence of bone destruction around the enthesis, and pain unresponsive to a trial of analgesics and physical therapy, were evaluated by closed or open biopsy for tuberculosis. A staging system is proposed for biopsy-proven tuberculosis of the enthesis. RESULTS: Between 2006 and 2010, we treated 14 patients with tuberculosis of the tendon-bone junction. Biopsy-proven cases of tuberculosis of the enthesis were administered anti-tubercular drugs for a period of one year. Sequestrectomy was performed in advanced lesions. The tendon-bone junction was rested until the features of its healing were clinically evident. The patients aged between 18 and 52 years were followed up for an average of 1.7 years after cessation of anti-tubercular drug therapy. They responded favourably, and none had recurrence of the disease. CONCLUSIONS: This study describes the tubercular involvement of the entheses, which heretofore has not been described in the literature. The rarity of its occurrence and lack of suspicion of an infectious aetiology in these locations frequently results in late diagnosis and incorrect initial treatment. This study also supports the "microtrauma theory" in the genesis of osteoarticular tuberculosis.

Frequent upregulation of cyclin D1 and p16 expression with low Ki-67 scores in multinucleated giant cells.

BACKGROUND/AIMS: Multinucleated giant cells are formed from the fusion of macrophages and are classified into foreign body-type giant cells (FBGCs), osteoclast-type giant cells (OCGCs) and Langhans-type giant cells (LHGCs). OCGCs display upregulated cyclin D1 expression with low Ki-67 activity. However, little is known about the expression of cell cycle regulators in the other types of multinucleated giant cells. We aimed to investigate the cell cycle status of multinucleated giant cells. METHODS: The immunohistochemical expressions of cyclin D1, p16(INK4a) and Ki-67 were analyzed in a total of 127 cases showing multinucleated giant cells. RESULTS: Cyclin D1 was overexpressed in 45 (88%) of 51 FBGC cases, 25 (86%) of 29 OCGC cases and 22 (47%) of 47 LHGC cases. p16(INK4a) showed diffuse nuclear and/or cytoplasmic overexpression in 45 (88%) of 51 FBGC cases, 27 (93%) of 29 OCGC cases and 24 (51%) of 47 LHGC cases. Ki-67 immunostaining was negative in almost all FBGC, OCGC and LHGC cases. CONCLUSION: This study demonstrates that FBGCs and OCGCs frequently show upregulation of cyclin D1 and p16(INK4a) expression with low Ki-67 scores. This suggests that multinucleated giant cells are arrested in the G1/S cell cycle transition.

Thalidomide prevents formation of multinucleated giant cells (Langhans-type cells) from cultured monocytes: possible pharmaceutical applications for granulomatous disorders.

Thalidomide is an effective drug for chronic inflammatory diseases, but the mechanism underlying its immunomodulatory action remains uncertain. Thalidomide has been reported to clinically improve chronic inflammatory granulomatous disorders. In such disorders, the granulomas consist of epithelioid cells, scattered lymphocytes and multinucleated giant cells (MNGC; Langhans-type cells). The present experimental approach permitted the reproduction of MNGC formation from peripheral blood monocytes and examination of thalidomides effect on it. MNGC can be effectively generated from monocytes cultured in the presence of interleukin-4 (IL-4) and macrophage colony-stimulating factor(M-CSF) for 14 days. Thalidomide can inhibit the formation of MNGC in a dose-dependent manner. MNGC formation was partly inhibited by the presence of neutralizing TNF-alpha antibody in the responses induced by IL-4 and M-CSF. Autocrinal TNF-alpha production and modulation of cadhelin expression to regulate cell adhesion might be involved in this inhibitory action of thalidomide. Our results support thalidomides clinical efficacy in the treatment of chronic granulomatous disorders (granulomatosis).

More experiences with the Tzanck smear test: cytologic findings in cutaneous granulomatous disorders.

BACKGROUND: Granulomatous dermatitis is a distinctive histopathologic cutaneous reaction pattern against various infectious and noninfectious agents. Cytologically, granulomatous dermatitis shows granulomas and multinucleated giant cells. Various etiologic agents of granulomatous diseases can also be identified. OBJECTIVE: We aimed to investigate Tzanck smear findings in granulomatous skin diseases. METHODS: Patients who had granulomas and/or multinucleated giant cells of Langhans, foreign body- and/or Touton type in Tzanck smear tests were included in the study. In these patients, Tzanck preparations were then further evaluated for additional cytologic findings. Samples stained with May-Grünwald-Giemsa stain were evaluated by the same dermatologist throughout the study. In some patients, methylene blue, Gram and/or Erlich-Ziehl-Nielsen stains were also performed. In all of the study cases, the final diagnosis was established after the evaluation of clinical and laboratory findings (including, when appropriate, potassium hydroxide examination; bacterial, leishmanial, and fungal cultures; histopathology; tuberculosis and leishmania polymerase chain reaction). We also calculated the sensitivity and specificity of the Leishman-Donovan body for cutaneous leishmaniasis. RESULTS: Over a 2-year period, 94 of 950 patients (9.9%) in whom Tzanck smear tests were performed had cytologic findings consistent with a granulomatous reaction. In 74 (78.7%) and 20 (21.3%) patients, the granulomatous reaction was due to infectious and noninfectious causes, respectively. Infectious causes included cutaneous leishmaniasis in 65 patients (87.8%), candidal granuloma in two patients, botyromycosis in two patients, and aspergillosis, blastomycosis, mucormycosis, leprosy, and cutaneous tuberculosis in one patient each. In 58 of 74 patients (78.4%) with infectious granulomatous dermatitis, the causes of the granulomas were identified. Noninfectious granulomatous reactions were due to granuloma annulare in 7 patients, sarcoidosis in 5 patients, a foreign body in 4 patients, necrobiosis lipoidica in 2 patients, and juvenile xanthogranuloma in 2 patients. In 17 of 20 patients (85%) with noninfectious granulomatous reactions, the cytologic findings were characteristic of the final diagnoses. The sensitivity and specificity of Leishman-Donovan bodies for cutaneous leishmaniasis were 76.9% and 100%, respectively. LIMITATIONS: All of the samples were evaluated by the same dermatologist throughout the study; therefore no comment could be made regarding the reliability of the Tzanck smear test. In addition, the sensitivity and specificity of Tzanck smear test findings for diseases other than cutaneous leishmaniasis could not be calculated because of an insufficient number of patients. CONCLUSION: The Tzanck smear test may be a useful diagnostic tool for certain granulomatous skin diseases.

Granuloma in sputum cytology of pulmonary tuberculosis: a case report.

BACKGROUND: Presence of epithelioid cell granuloma and Langhans' giant cells in sputum cytology in cases of pulmonary tuberculosis is of very uncommon occurrence. Only a few reports could be found in the English-language literature. CASE: A 73-year-old man, a chronic smoker for 50 years, reported to the medical out-patient department with complaints of cough and significant weight loss for the past 1 year. Routine sputum cytology revealed epithelioid cell granuloma along with Langhans' giant cells. Ziehl-Neelsen stain showed presence of multiple acid-fast bacilli (AFB). Chest radiography showed opacity of the airways and areas of cavitations in bilateral parahilar location and diffuse nodular opacity in bilateral lung fields. CONCLUSION: Albeit of very rare occurrence, presence of epithelioid cell granuloma and Langhans' giant cells, along with demonstration of AFB in routine sputum cytology, is capable of providing a conclusive diagnosis in appropriate clinical context, obviating the need of additional investigation.

A rare case of sarcoid-like reaction of lymph nodes associated with squamous cell carcinoma of alveolar mucosa.

Non-necrotizing granulomas are occasionally seen in patients with certain malignant disorders and are termed as "sarcoid-like reaction," which have many similarities with sarcoidosis. Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by organ involvement and interference of organ function by granuloma or fibrosis. Sarcoidosis is occasionally found in a variety of malignant diseases with an overall incidence of 4.4% in carcinoma patients. We present here a rare case of moderately differentiated squamous cell carcinoma of alveolar mucosa with regard to mandible associated with sarcoid-like reaction of cervical lymph nodes in a female patient in the absence of clinical evidence of systemic sarcoidosis. The relevant literature including pathogenesis is also discussed.

Generalized sarcoidosis in two horses.

Equine sarcoidosis is a rare disorder usually characterized by exfoliative dermatitis, moderate to severe wasting, and sarcoidal granulomatous inflammation of multiple organ systems. It has an unknown aetiopathogenesis. The condition is not related to equine sarcoid. This case report describes generalized cutaneous and systemic sarcoidosis in an 11-year-old Trakehner mare (case A) and in a 7-year-old Dutch Warmblood gelding (case B). Case A was presented with cutaneous sarcoidosis on the head and body and was diagnosed on the basis of histological examination of skin. Case B presented with multiple subcutaneous nodules (2-15 cm in diameter) and the diagnosis was established at postmortem examination. Both horses showed distinctive histology of the skin with extensive lymphohistiocytic infiltration and Langhans-type multinucleated giant cells. Haematology and biochemistry revealed a normal total white blood cell count with a right shift in both horses. Case B was anaemic and had a slightly elevated total protein concentration with hyperglobulinaemia. Both horses were unresponsive to corticosteroids and were euthanized.

Solitary intraventricular tuberculoma in adults.

Intracranial tuberculoma is typically located in the parenchyma. Lesions limited to the ventricular system are uncommon. It is difficult to make a differential diagnosis from other lesions if no systemic tuberculosis is present. This study investigates a case of solitary intraventricular tuberculoma in a 19-year-old female patient with an initial clinical symptom of progressive headache. Cranial computed tomography revealed a strongly enhanced lesion in the lateral ventricle. Histopathology of the tumor demonstrated chronic inflammation, caseous necrosis, epithelioid cells and Langhans' giant cell. The culture study grew M. Tuberculosis. Solitary intraventricular tuberculoma in adults is extremely rare. Medical treatment is the preferred management method of this disease, and surgical intervention should be considered in certain situations.