Background
Tuberculosis is a special type of bacterial infection caused by a strain known as Mycobacterium tuberculosis. In spite of significant advances in prevention and drug treatment, it still remains a major public health threat. It is estimated that 1/3 of the world's population is infected and about 3 million people die from the disease each year. The advent of AIDS as well as multi-drug resistant strains has brought this disease to the forefront of medicine.
OUTLINE
PATHOGENESIS CHARACTERIZATION Facial granulomatous diseases Am J Dermatopathol 2001;23:8-15
Four cases examined with nested PCR
2/4 positive
Poor correlation between PCR results and clinical outcome
DISEASE ASSOCIATIONS CHARACTERIZATION TUBERCULOUS EPIDIDYMO-ORCHITIS
Department of Pathology, Nelson R Mandela School of Medicine, University of KwaZulu Natal and National Health Laboratory Services, Durban, KwaZulu Natal, South Africa.
J Cutan Pathol. 2007 Nov;34(11):830-6. Abstract quote
Background: Tuberculids are rarely associated with male genital tract tuberculosis (TB). Tuberculous epididymo-orchitis (TBEO) has been associated rarely with papulonecrotic tuberculid (PNT) but not with erythema induratum (EI) or the simultaneous occurrence of different tuberculids.
Methods: A retrospective assessment of tuberculids that occurred with underlying TBEO was carried out.
Results: Five patients, four with one and one with two skin biopsies, with clinical diagnoses of PNT (two), EI (one), impetigo (two) and calf ulcer (one), formed the study cohort. Histopathological evaluation confirmed PNT and EI in four and two skin biopsies, respectively. Two patients who returned for follow-up were commenced on anti-tuberculous therapy. All patients sought medical attention 3-34 months later for tender right-sided (two) and left-sided (three) testicular masses. Orchidectomy was undertaken following a poor clinical response to empirical treatment with trimethoprim sulfamethoxazole. Pathological examination of the testis and epididymis confirmed TBEO. The patients were initiated on anti-tuberculous therapy. There was dramatic healing of the skin lesions.
Conclusion: Tuberculids are a sentinel cutaneous manifestation of visceral TB and a valuable external audit of treatment compliance and response. Heightened recognition of and more rigorous genitourinary tract investigation are necessary to identify occult or asymptomatic TBEO as the underlying cause of tuberculids.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION General VARIANTS SKINJ Am Acad Dermatol 1995;33:433-440
Occurs by exogenous inoculation, endogenous spread, and lymphatic or hematogenous dissemination
Primary inoculation tuberculosisAccounts for <5% of total cases of primary tuberculosis
Nodule develops within 2-4 weeks after inoculation leading to a well-demarcated ulcer that heals with scarring
May have associated lymphadenitis
Acute miliary tuberculosis
(Tuberculosis cutis miliaris disseminata)Clin Infect Dis 1996;23:706-710
Rare and usually fatal
More common in infants and childrenIncreased association with AIDS patients
Frequent on trunk, buttocks, genitalia, and thighs
Small papules with capped vesicles that rupture, crust, and heal with scarring Lupus vulgarisReinfection tuberculosis in previously sensitized patients
Presents with plaques, hypertrophic, ulcerative, vegetating, and papulonodular
May involve mucous membranes with destruction of cartilageSolitary or multiple small soft brownish papules with characteristic apple-jelly color on diascopy
Papules enlarge and become infiltrative with central atrophy
Tuberculosis verrucous cutisReinfection tuberculosis that occurs at sites of trauma in previously infected patients
Usually asymptomatic, erythematous papules that develop into verrucous plaque with fissures draining pus
Not usually associated with lymphadenopathy
Scrofuloderma
(Tubercullosis colliquativa cutis)Reactivation form of tuberculosis
Sinus tract in subcutaneous tissue, usually overlying a lymph node
- Multiple metastatic tuberculosis abscesses in a patient with Pott disease and lung tuberculosis: a case report.
Saral Y, Coskun BK, Ozturk P, Bulut Y, Cobanoglu B.
Department of Dermatology, Firat University, Elazig, Turkey.
J Cutan Pathol. 2005 Oct;32(9):629-33. Abstract quote
The incidence of tuberculosis in Western countries is rising, and continued vigilance together with an awareness of its protean manifestations is essential. Cutaneous tuberculosis is a relatively rare manifestation of the disease, accounting for only 1% of extrapulmonary cases of tuberculosis and 0.14% of all reported cases of tuberculosis.
A 19-year-old male patient was admitted to our clinic with skin lesions both at the front and at the back of his body. With clinical findings, histopathology, polymerase chain reaction, PA lung graph, and computerised tomography, the patient was diagnosed with metastatic tuberculosis abscess associated with lung tuberculosis and Pott's disease. Antituberculosis drugs were administered.
An increased awareness of the re-emergence of cutaneous tuberculosis will allow for the proper diagnosis and management of this increasing common skin disorder.
HISTOLOGICAL TYPES CHARACTERIZATION General VARIANTS Tuberculids Represent hypersensitivity response to circulating antigens of the tubercule bacillus Micropapular Papulo-necrotic Nodular Lichen scrofulosorumVariant of micropapular form
Grouped scaly follicular tiny 1-2 mm papules
Small tuberculoid granulomas in periadnexal or focally lichenoid pattern
Superficial and deep perivascular and periadnexal, slight to moderately dense lymphocytic infiltrate with epithelioid histiocytes
Epidermis may show slight spongiosis and parakeratosis
Neutrophils may collect in epidermis above the granulomasMYCOBACTERIUM SPINDLE CELL PSEUDOTUMOR
Pseudotumor resulting from atypical mycobacterial infection: a "histoid" variety of Mycobacterium avium-intracellulare complex infection.Wood C, Nickoloff BJ, Todes-Taylor NR.
Am J Clin Pathol 1985 Apr;83(4):524-7 Abstract quote A 54-year-old immunosuppressed cardiac transplant recipient with a six-month history of progressive swelling of the hand, with nodules and linear lymph node chain enlargement, diagnosed as a sporotrichoid Mycobacterium avium-intracellulare pseudotumor is described. The microscopic features closely resembled the previously described histoid variety of lepromatous leprosy.
Routine hematoxylin and eosin staining suggested a spindle cell neoplasm rather than an infectious or inflammatory process. An infectious etiology was pursued on the basis of the clinical setting.
Mycobacterial spindle cell pseudotumor of lymph nodes.
Chen KT.
Department of Pathology, Saint Agnes Medical Center, Fresno, California 93720.
Am J Surg Pathol 1992 Mar;16(3):276-81 Abstract quote Two cases of spindle cell pseudotumor in the lymph nodes of patients with acquired immunodeficiency syndrome caused by mycobacterial infection are reported and the literature reviewed.
The lesions mimicked neoplasms because they were composed predominantly of spindle cells arranged in a storiform pattern. Most of the spindle cells were phagocytic cells that contained large amounts of mycobacteria.
It is important for the pathologist to recognize the lesion so that a prompt tissue diagnosis can be provided because specific therapy is available.
Fine needle aspiration cytology of mycobacterial spindle cell pseudotumor. A case report.Corkill M, Stephens J, Bitter M.
Department of Pathology, University of Colorado Health Sciences Center, Denver.
Acta Cytol 1995 Jan-Feb;39(1):125-8 Abstract quote We report a case of mycobacterial spindle cell pseudotumor (MSP) in a lymph node from an acquired immunodeficiency syndrome patient diagnosed by fine needle aspiration (FNA). The FNA cytology was characterized by spindle cell proliferation without the typical foamy histiocytes usually seen in mycobacterial infections and mimicked a mesenchymal neoplasm, particularly Kaposi's sarcoma.
This case illustrates the importance of including MSP in the differential diagnosis of lymph node FNAs from immunocompromised patients, particularly those that show spindle cell proliferation suspicious for Kaposi's sarcoma or another mesenchymal neoplasm.
Spindle cell tumors associated with mycobacteria in lymph nodes of HIV-positive patients: 'Kaposi sarcoma with mycobacteria' and 'mycobacterial pseudotumor'.Logani S, Lucas DR, Cheng JD, Ioachim HL, Adsay NV.
Department of Pathology, Harper Hospital, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan 48201, USA.
Am J Surg Pathol 1999 Jun;23(6):656-61 Abstract quote Patients infected with HIV often have unusual manifestations of common infections and neoplasms. One such example is "mycobacterial pseudotumor," an exuberant spindle cell lesion induced in lymph nodes by mycobacteria. Kaposi sarcoma also produces a spindle cell proliferation in lymph nodes of HIV-positive patients. These two entities must be differentiated from one another because of differences in treatment and prognosis.
We report here, however, three cases of intranodal Kaposi sarcoma with simultaneous mycobacterial infection, the occurrence of which has not been clearly documented. For comparison, we also studied three cases of mycobacterial pseudotumor, of which 14 cases have been described to date. There was considerable histologic overlap between these two lesions. Acid-fast bacilli were present in all cases, predominantly in the more epithelioid histiocytes in the cases of Kaposi sarcoma, and in spindle and epithelioid cells in the cases of mycobacterial pseudotumor.
The morphologic features that favored Kaposi sarcoma over mycobacterial pseudotumor were the prominent fascicular arrangement of spindle cells and slitlike spaces, the lack of granular, acidophilic cytoplasm, and the presence of mitoses. Immunohistochemistry was a reliable adjunct study in the differential diagnosis, as the spindle cells in mycobacterial pseudotumor were positive for S-100 protein and CD68 whereas those of Kaposi sarcoma were CD31- and CD34-positive but negative for S-100 protein and CD68. Awareness that Kaposi sarcoma may coexist with mycobacterial infection in the same biopsy specimen is important because these lesions may be misdiagnosed as mycobacterial pseudotumor.
The clinical impact of distinguishing between Kaposi sarcoma with mycobacteria and mycobacterial pseudotumor is significant because the presence of Kaposi sarcoma alters treatment and prognosis.
Mycobacterial spindle cell pseudotumor of the brain: a case report and review of the literature.Morrison A, Gyure KA, Stone J, Wong K, McEvoy P, Koeller K, Mena H.
Armed Forces Institute of Pathology, Department of Neuropathology, Washington, DC 20306-6000, USA.
Am J Surg Pathol 1999 Oct;23(10):1294-9 Abstract quote Spindle cell pseudotumors found in the skin, lymph nodes, bone marrow, spleen, lungs, and retroperitoneum have been reported recently in immunosuppressed patients, including those with acquired immunodeficiency syndrome.
The authors report a similar lesion limited to the brain in a 38-year-old human immunodeficiency virus-negative man receiving steroid therapy for treatment of sarcoidosis. Histopathologically the lesions were composed of spindle and epithelioid histiocytes, small foci of necrosis, and numerous acid-fast bacilli. The acid-fast bacilli were determined by culture and polymerase chain reaction to be Mycobacterium avium intracellulare.
Because of the uncommon histologic appearance of this lesion and the potential for treatment if recognized, mycobacterial spindle cell pseudotumors should be included in the differential diagnosis of spindle cell lesions in the brain in immunosuppressed patients.
Mycobacterial spindle cell pseudotumor of the appendix vermiformis in a patient with aids.Basilio-de-Oliveira C, Eyer-Silva WA, Valle HA, Rodrigues AL, Pinheiro Pimentel AL, Morais-De-Sa CA.
Departments of Pathology and Clinical Immunology, Gaffre e Guinle University Hospital, Rio de Janeiro, RJ, Brazil.
Braz J Infect Dis 2001 Apr;5(2):98-100 Abstract quote Mycobacterial pseudotumor (MP) is a rare pathologic presentation of both Mycobacterium tuberculosis and non-tuberculous mycobacterial disease, hitherto reported to occur only in immunosuppressed patients with or without human immunodeficiency virus infection. This lesion shares close pathologic resemblance to certain mesenchymal neoplasms, particularly Kaposi's sarcoma (KS), from which it must be properly differentiated due to distinct prognosis and therapy.
We report a case of MP obliterating the lumen of the appendix vermiformis in a 34-year-old patient who died of complications of AIDS at our hospital in Rio de Janeiro. A total of 24 cases of MP (including our patient) have been described in the literature. MP has been found especially in lymph nodes, but extranodal lesions have been described in the skin, spleen, lung, bone marrow, brain and, in our patient, the appendix vermiformis.
We offer a review of the other 23 published case reports of MP in both HIV-infected and uninfected patients and discuss the pathologic features that differentiate MP from KS.
PROGNOSIS CHARACTERIZATION
TREATMENT CHARACTERIZATION GENERAL BCG VACCINE
Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study.
Aronson NE, Santosham M, Comstock GW, Howard RS, Moulton LH, Rhoades ER, Harrison LH.
Department of Medicine, Infectious Disease Division, Uniformed Services University of the Health Sciences, Bethesda, Md 20814, USA.
JAMA. 2004 May 5;291(17):2086-91. Abstract quote
CONTEXT: The duration of protection from tuberculosis of BCG vaccines is not known.
OBJECTIVE: To determine the long-term duration of protection of a BCG vaccine that was previously found to be efficacious.
DESIGN: Retrospective record review using Indian Health Service records, tuberculosis registries, death certificates, and supplemental interviews with trial participants.
SETTING AND PARTICIPANTS: Follow-up for the period 1948-1998 among American Indians and Alaska Natives who participated in a placebo-controlled BCG vaccine trial during 1935-1938 and who were still at risk of developing tuberculosis. Data from 1483 participants in the BCG vaccine group and 1309 in the placebo group were analyzed.
MAIN OUTCOME MEASURES: Efficacy of BCG vaccine, calculated for each 10-year interval using a Cox regression model with time-dependent variables based on tuberculosis events occurring after December 31, 1947 (end of prospective case finding). RESULTS: The overall incidence of tuberculosis was 66 and 138 cases per 100 000 person-years in the BCG vaccine and placebo groups, respectively, for an estimate of vaccine efficacy of 52% (95% confidence interval, 27%-69%). Adjustments for age at vaccination, tribe, subsequent BCG vaccination, chronic medical illness, isoniazid use, and bacille Calmette-Guerin strain did not substantially affect vaccine efficacy. There was slight but not statistically significant waning of the efficacy of BCG vaccination over time, greater among men than women.
CONCLUSION: In this trial, BCG vaccine efficacy persisted for 50 to 60 years, suggesting that a single dose of an effective BCG vaccine can have a long duration of protection.
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
Acid Fast-This is a peculiar histologic staining pattern associated with the cell walls of mycobacteria. Common stains used are Fite and Ziehl-Nielson stains.
Ghon Complex-This is both a clinical and radiologic term identified as primary infection within a calcified scar in the lung associated with a hilar (adjacent to the lung) lymph node.
Miliary-This is a pattern of spread through the bloodstream of an infected patient. As it disseminates, it leads to hundreds of small yellow-white lesions studding many organs. The name derives from millet seeds, fed to birds.
Pott's Disease-A variant of the disease affecting the vertebral (spinal) column. Advanced disease may lead to considerable bony destruction with collapse and impingement of the spinal nerves. Fistulas or channels may form along the muscles which line the vertebral columns leading to abscesses.
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Last Updated November 15, 2007
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