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1.  Tuberculosis of the entheses 
International Orthopaedics  2012;36(11):2373-2378.
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.
doi:10.1007/s00264-012-1657-8
PMCID: PMC3479276  PMID: 22976594
2.  Progressive ocular inflammation following anti-tubercular therapy for presumed ocular tuberculosis in a high-endemic setting 
Eye  2013;27(5):657-662.
Purpose
To analyze the incidence and clinical course of patients developing progressive ocular inflammation following anti-tubercular therapy (ATT) for presumed ocular tuberculosis (TB).
Methods
Retrospective analysis of medical records of patients who received ATT for presumed ocular TB and completed at least 12 months follow-up after initiation of ATT. The diagnosis of presumed ocular TB was based on presence of ocular signs suggestive of TB, evidence of past tubercular infection, and exclusion of mimicking clinical entities. All patients received a combination of ATT and corticosteroid therapy. Primary outcome measure was progression (worsening) of ocular inflammation, defined as a two-step increase in level of inflammation (anterior chamber/ vitreous) or the appearance of new lesions following initiation of ATT.
Results
A total of 106 patients (64 male, 42 female) received ATT for presumed ocular TB. Twenty-six (24.5%) patients developed progressive intraocular inflammation following ATT. Primary diagnoses in these patients were: anterior uveitis (n=1), intermediate uveitis (n=9), retinal vasculitis (n=3), serpiginous-like choroiditis (n=7), multifocal choroiditis (n=2), and pan-uveitis (n=4). Following progressive inflammation, diagnosis was revised in two patients (7.7%)—both responded to alternative therapy. Of the rest, majority (n=16; 61.5%) resolved with escalation of corticosteroid therapy. Five patients (19.2%)—all having intermediate uveitis—required therapeutic vitrectomy for resolution. Three patients (11.5%) had persistent inflammation at end of follow-up period.
Conclusion
Progressive inflammation following ATT for presumed ocular TB is common. It generally resolves on escalation of corticosteroid therapy. Cases not responding to increased immunosuppression need to be re-investigated to rule out a nontubercular cause.
doi:10.1038/eye.2013.5
PMCID: PMC3650289  PMID: 23449506
inflammation; tuberculosis; ocular; anti-tubercular therapy; progressive inflammation
3.  Autoantibody with Cross-Reactivity between Insulin and Ductal Cells May Cause Diabetic Mastopathy: A Case Study 
Case Reports in Medicine  2012;2012:569040.
Lymphocytic mastopathy or diabetic mastopathy is a benign breast disease characterized by dense fibrosis, lobular atrophy, and aggregates of lymphocytes in a periductal and perilobular distribution. The condition usually affects women with a long history of diabetes mellitus (DM) and also those with autoimmune disorders. While the pathogenesis is unknown, a particular type of class II human leukocyte antigen has been associated with this disease. Herein, we report a case of diabetic mastopathy which clinically and radiologically mimicked primary breast neoplasms. The patient was a 74-year-old woman with a 31-year history of DM type II who presented with multiple firm lumps in bilateral breasts. Findings from mammography, ultrasonography, and magnetic resonance imaging of the breasts revealed an abnormal appearance which suspiciously resembled malignancy. An aspiration cytology specimen showed atypical accumulation of lymphoid cells, leading us to suspect lymphoma. Histology of an excisional biopsy showed the characteristic appearance of lymphocytic mastopathy, which predominantly consisted of B-lymphocytes. Autoantibodies in her serum reacted positively against her ductal epithelium as well as other diabetic and nondiabetic breast ductal cells. An antigen absorption test with insulin revealed attenuating intensity according to insulin concentration. These anti-insulin antibodies produced in the DM patient may cause ductitis because of antigen cross-reactivity.
doi:10.1155/2012/569040
PMCID: PMC3346992  PMID: 22577391
4.  Medical imaging. 
Postgraduate Medical Journal  1991;67(786):334-346.
There is now a wide choice of medical imaging to show both focal and diffuse pathologies in various organs. Conventional radiology with plain films, fluoroscopy and contrast medium have many advantages, being readily available with low-cost apparatus and a familiarity that almost leads to contempt. The use of plain films in chest disease and in trauma does not need emphasizing, yet there are still too many occasions when the answer obtainable from a plain radiograph has not been available. The film may have been mislaid, or the examination was not requested, or the radiograph had been misinterpreted. The converse is also quite common. Examinations are performed that add nothing to patient management, such as skull films when CT will in any case be requested or views of the internal auditory meatus and heal pad thickness in acromegaly, to quote some examples. Other issues are more complicated. Should the patient who clinically has gall-bladder disease have more than a plain film that shows gall-stones? If the answer is yes, then why request a plain film if sonography will in any case be required to 'exclude' other pathologies especially of the liver or pancreas? But then should cholecystography, CT or scintigraphy be added for confirmation? Quite clearly there will be individual circumstances to indicate further imaging after sonography but in the vast majority of patients little or no extra information will be added. Statistics on accuracy and specificity will, in the case of gall-bladder pathology, vary widely if adenomyomatosis is considered by some to be a cause of symptoms or if sonographic examinations 'after fatty meals' are performed. The arguments for or against routine contrast urography rather than sonography are similar but the possibility of contrast reactions and the need to limit ionizing radiation must be borne in mind. These diagnostic strategies are also being influenced by their cost and availability; purely pragmatic considerations are not infrequently the overriding factor. Non-invasive methods will be preferred, particularly sonography as it is far more acceptable by not being claustrophobic and totally free of any known untoward effects. There is another quite different but unrelated aspect. The imaging methods, apart from limited exceptions, cannot characterize tissues as benign or malignant, granulomatous or neoplastic; cytology or histology usually provides the answer. Sonography is most commonly used to locate the needle tip correctly for percutaneous sampling of tissues. Frequently sonography with fine needle aspiration cytology or biopsy is the least expensive, safest and most direct route to a definitive diagnosis. Abscesses can be similarly diagnosed but with needles or catheters through which the pus can be drained. The versatility and mobility of sonography has spawned other uses, particularly for the very ill and immobile, for the intensive therapy units and for the operating theatre, as well in endosonography. The appointment of more skilled sonographers to the National Health Service could make a substantial contribution to cost-effective management of hospital services. Just when contrast agents and angiography have become safe and are performed rapidly, they are being supplanted by scanning methods. They are now mainly used for interventional procedures or of pre-operative 'road maps' and may be required even less in the future as MRI angiography and Doppler techniques progress. MRI will almost certainly extent its role beyond the central nervous system (CNS) should the equipment become more freely available, especially to orthopaedics. Until then plain films, sonography or CT will have to suffice. Even in the CNS there are conditions where CT is more diagnostic, as in showing calculations in cerebral cysticercosis. Then, too, in most cases CT produces results comparable to MRI apart from areas close to bone, structures at the base of the brain, in the posterior fossa and in the spinal cord. Scintigraphy for pulmonary infarcts and bone metastases and in renal disease in children plays a prominent role and its scope has increased with new equipment and radionuclides. Radio-immunoscintigraphy in particular is likely to expand greatly not only in tumour diagnosis but also in metabolic and infective conditions. Whether the therapeutic implications will be realized is more problematic. The value of MRS and NM for metabolic studies in clinical practice is equally problematical, although the data from cerebral activity are extremely interesting. While scanning has replaced many radiographic examinations, endoscopy has had a similar effect on barium meals and to a lesser extent on barium enemas. The combined visual/sonographic endoscope is likely to accelerate this process. There is no doubt that over the last 2 decades medical imaging has changed the diagnostic process, but its influence on the outcome of disease other than infections is less certain and probably indefinable. Data concerning the comparative efficacy in terms of patient outcome for each of the imaging techniques would be of considerable interest and a great help in determining diagnostic strategies.
PMCID: PMC2398810  PMID: 2068025
5.  FURTHER STUDIES ON THE OPHTHALMO-TUBERCULIN REACTION IN CATTLE 
Our conclusions differ in a few points from those of our first work on this subject. We are able to sum up our observations in this series of experiments as follows: 1. The ophthalmo-tuberculin test is of limited value in the diagnosis of tuberculosis in cattle. In some cases the reaction is very slight (hyperæmia). In others more pronounced congestion with profuse exudates are noted. Accuracy of observation is important. We are inclined to rely primarily on the results of the first instillation of tuberculin. Second instillations in a few instances elicit reaction in non-tubercular animals. 2. In the majority of animals tested the reaction increased in its intensity with each subsequent instillation of tuberculin. This fact indicates the development of a local hypersusceptibility or anaphylaxis associated with a partial immunity; von Pirquet calls this condition "allergie" (9). 3. It is possible in some cases to create a condition of "allergie" in healthy cattle, when spaced instillations of tuberculin are made. It is evident, therefore, that the result of the first instillation of tuberculin should be made the only basis of diagnosis. Rosenau and Anderson (II) have recently called attention to this point in regard to the human subject. 4. When repeated instillations of tuberculin are made on the conjunctiva at short intervals (twenty-four hours, etc.) a local immunity results (No. 3D et al.). If the instillations are separated two weeks or more anaphylaxis results. 5. We, therefore, hold that if tuberculin (0.1 cubic centimeter) is carefully instilled into the conjunctival sac and if careful comparison of the instilled eye with the opposite eye shows that a reaction of varying intensity results in from ten to twelve hours after the first instillation, a tubercular lesion is present. 6. In our first report (7) we were inclined to believe that subcutaneous tubercular injection given previous to the ocular test would slightly inhibit it. We have since become convinced that this is true only to a limited extent, and that in some cases the ophthalmo-reaction is exaggerated by a subcutaneous injection of tuberculin. 7. The primary ophthalmo-tuberculin reaction is in direct proportion to the extent of the tubercular processes in the body. The more extensive the tubercular processes, the more anaphylactic the animal is. This is in direct variance with the condition in the usual subcutaneous tuberculin test. (See Necropsy Report.) 8. We are inclined to believe that the ophthalmo-tuberculin test will reveal tuberculosis at as early a state as the usual subcutaneous test. 9. The ophthalmo-reaction is of no value in determining whether vaccinated cattle are actively tubercular or not, or in demonstrating any hypersusceptibility in the offspring of tubercular cattle. 10. The cutaneous test from our brief series of experiments does not seem to be as accurate as the ophthalmic test. This conclusion has been reached by several investigators.
PMCID: PMC2124543  PMID: 19867152
6.  Primary Tuberculosis in Soft Palate: Case Report of a Rare Entity 
A 40-year-old male patient presented to our clinic with history of dysphagia and ulceration in the palate for two months. After history-taking and thorough clinical examination, investigations like routine blood parameters, chest skiagram, sputum for acid-fast bacilli, ultrasonography of the abdomen, and biopsy from the palatal lesion were performed. No evidence in support of pulmonary or abdominal tuberculosis was found. Histopathological examination of the biopsy revealed granulomatous inflammation with Langhans giant cells and caseation necrosis. Diagnosis of primary tuberculosis of soft palate was made. Anti- tubercular regimen (CAT I) for 6 months was prescribed, and we got a dramatic response noted within 15 days. As isolated tuberculosis of soft palate is a very rare entity, one should, therefore, consider it in any case of chronic ulcer of the soft palate. Response to CAT 1 was excellent in our case.
doi:10.4103/0019-5154.135543
PMCID: PMC4103304  PMID: 25071287
Granuloma; primary tuberculosis; soft palate
7.  A CONTRIBUTION TO THE CHEMOTHERAPY OF TUBERCULOSIS  
Judging from the macroscopic and microscopic study of the animals treated with the liquid, its action upon the tubercular lesions seems to be about as follows: The effect of a single injection upon the lesions is either negative or inconspicuous. But after repeated injections of the preparation the congestion and leukocytic infiltration about the lesions are markedly decreased, the cheesy material resulting from degeneration of the lesions and other degeneration products are in process of absorption, and young connective tissue is being actively produced in the periphery. While these changes are taking place the number of the bacilli is also being reduced until finally they can no longer be detected on microscopic examination. Hence it appears that while the preparation may lack bactericidal action in vivo powerful enough to destroy all the bacilli at one injection, yet repeated infusions may nevertheless bring about the destruction of all the bacilli and the modification of the tubercular lesion into that of the suspended stage or even into the healed condition. Whether, therefore, the preparation brings about these results directly by killing the bacilli or indirectly by favoring the healing processes of the body, nevertheless it has power to inhibit the growth of or annihilate entirely the bacilli in vivo. The experiments reported leave no doubt that Liquid D is capable of bringing about the healing of experimental tubercular lesions; but thus far that most important problem in chemotherapeutics, namely, the extent of the cure produced, has not been solved. The experiments indicate that sterility of the tissues as far as microscopic examinations go has been secured; but microscopic examination is not after all an absolute test of sterility. In order to test this point, emulsions were made of the lungs, liver, spleen, and other organs of Treated Animals 134 and 135 (Table VII), and they were inoculated into the abdominal cavity of guinea pigs. Some of the animals receiving the emulsion developed tuberculosis, and therefore absolute sterility of the treated animals had not been obtained in these instances. The problem of the destination and distribution of the preparation in the body of the treated animal, as well as its action against the tubercle bacilli, lesions, and the tubercular organs of the infected guinea pigs, is now being studied further with results to be reported at some future time.
PMCID: PMC2125458  PMID: 19868032
8.  Fulminant holocord intramedullary tubercular abscess with enigmatic presentation 
Background:
Intramedullary and subarachnoidal tubercular abscesses are rare forms of spinal tuberculosis as compared with extradural collections secondary to vertebral tuberculosis.
Case Description:
We herein present a 33-year-old, apparently healthy male patient who presented clinically as transverse myelitis, with a lesion at detected at conus cauda, developing fulminant holocord intramedullary tubercular abscess, treated with surgical evacuation and much later with anti-tubercular drugs. Atypical clinical, serological, imaging findings in addition to lack of knowledge of occurrence of fulminant intramedullary tuberculosis led to the delay in starting anti-tubercular treatment.
Conclusion:
Early diagnosis requires a high index of suspicion, search for a primary focus of tubercular infection, investigation with magnetic resonance imaging (MRI) of spinal cord, biopsy, and confirmation with microscopy and culture, even in immunocompetent individuals. Early diagnosis, prompt treatment with surgical evacuation of abscess, and anti-tubercular drugs can lead to a good neurological recovery.
doi:10.4103/2152-7806.109506
PMCID: PMC3622373  PMID: 23607054
Filum terminale; intramedullary; spinal tuberculosis; subarachnoidal; tubercular abscess
9.  Hemiplegic/monoplegic presentation of cervical spine (C1-C2) tuberculosis 
European Spine Journal  2014;10(6):540-544.
Abstract.
Tuberculosis of the craniovertebral region is very rare. Neural deficit in this region is reported in between 24% and 64% of cases, and mainly takes the form of quadriparesis. Hemiplegic and monoplegic presentation among this set of patients is rarer. Out of 32 patients treated at our institution between May 1989 and February 2001, only one had hemiplegia, while two had monoplegia. These three cases are discussed. Case 1 involved a 45-year-old woman who presented with hemiplegia following a trivial fall. Plain radiographs and computed tomographic (CT) scans of the skull appeared normal, but CT scans of C1-C2 and the craniovertebral junction revealed destruction of the dens and atlantoaxial subluxation. The patients in cases 2 and 3 had monoplegia. Plain radiographs in both cases showed an increased prevertebral soft tissue shadow in front of C1-C2. CT in case 2 and magnetic resonance imaging (MRI) in case 3 revealed destruction of the arch of C1 and the dens, with subluxation. All three patients were successfully treated with rest, skull traction, anti-tubercular drugs and suitable braces. Case 3 required stabilization. All three patients achieved complete neural recovery. Patients 1, 2 and 3 had 22, 48 and 4 months' follow-up respectively. Patient 3 was subsequently transferred to a neurosurgery ward for stabilization of the occipito-C3 vertebrae. Hemi/monoplegic presentation is extremely rare; no author in the literature is able to give reason for the rarity or the pathomechanics of the condition. We believe that if medullary cervical junctional involvement extends slightly higher (in rare circumstances), with involvement of one of the branches of the vertebral or lower basilar artery, medial medullary syndrome will occur, sparing medial lemniscus and emerging hypoglossal nerve fibres. Thus the pyramids will be involved, causing contralateral hemiparesis, and if the pyramids are selectively involved, it will cause contralateral monoparesis.
doi:10.1007/s005860100340
PMCID: PMC3611535  PMID: 11806397
Hemiplegia Monoplegia Tuberculosis of spine Cervical spine Atlanto axial junction
10.  Diagnosis and treatment of hepatic tuberculosis: report of five cases and review of literature 
Hepatic tuberculosis is uncommon, lack of specific clinical manifestations and imaging features, so it can easily be misdiagnosed in clinical. Herein, we discuss variety of its forms and summarize the diagnosis and treatment of hepatic tuberculosis in this paper. Five cases of hepatic tuberculosis are described. The diagnosis, treatment and outcome of the patients are discussed. Image examination associated with image-guided fine needle aspiration biopsy is the best diagnostic method. In our center, three patients underwent needle biopsy and confirmed hepatic tuberculosis. In addition, two patients preoperative misdiagnosed as cholangiocarcinoma were confirmed hepatic tuberculosis by postoperative pathology. Three patients underwent surgical procedures along with anti-tubercular drug therapy, two patients received only anti-tubercular drug therapy. The renal post-transplantation patient with hepatic tuberculosis eventually died of multiple organ failure (MODS). The other four patients were followed for 48~120 months, yielding no recurrence of hepatic tuberculosis. In conclusion, hepatic tuberculosis usually associated with atypical clinical manifestations. Image examination associated with image-guided fine needle aspiration biopsy is the best diagnostic method. Anti-TB treatment is effective in most of cases. However, if there are indications for surgery or difficult to diagnose, surgical procedures along with anti-tubercular drug therapy could be adopted.
PMCID: PMC3798224  PMID: 24179582
Liver mass; tuberculoma; tuberculosis; TB; anti-TB
11.  THE OPHTHALMO-TUBERCULIN REACTION IN CATTLE 
The conclusions to be deduced from this brief series of experiments are as follows: 1. The ophthalmo-tuberculin reaction is of some value for diagnosis of tuberculosis in cattle. A characteristic conjunctivitis with fibrinous exudation coming on from six to eight hours, reaching a maximum in from sixteen to twenty-four hours and disappearing in forty-eight hours, is noted in tubercular animals. 2. The reaction is more pronounced in those animals which have not been recently tested with tuberculin. With this reaction as with the usual tuberculin test one injection and reaction probably inhibit a second reaction during a period from six weeks to a year. The ordinary tuberculin test does not seem to interfere to any great extent with the ophthalmo-tuberculin test at least within four weeks. Class B, though recently tested, showed the reaction, although not to the extent of Class A, which was tested some time ago. The tuberculin test occasionally prevents absolutely a second reaction, and usually no second reaction occurs within six weeks to a year, as before stated. 3. In cattle recently tested with tuberculin by the subcutaneous method the ophthalmo-tuberculin reaction is only slightly reduced in its intensity. The ophthalmic test may possibly serve as a means of diagnosis of tuberculosis in cattle which have been tested with tuberculin by the ordinary method and will not react a second time, or where tuberculin has been injected into cattle in order that they may clear a second test. Another possibility must not be overlooked in this connection. It is well known that animals which have a slight tubercular infection often show a very marked and typical reaction to the tuberculin test as it is usually made, and those animals which show themselves clinically to be in the advanced stages of tuberculosis often show only a very slight reaction. The animals in Class B are in the advanced stages of tuberculosis and this fact might perhaps account for the lower intensity of the reaction. The exact cause of the lower reaction in these cattle can only be determined by further experimentation. 4. No constitutional disturbance being noticed in any of the cattle tested, that is, no rise in temperature, loss of appetite or falling off in the production of milk, it is evident that the instillation of tuberculin into the eye does not produce the general reaction which attends in some cases the subcutaneous injection of tuberculin, and is therefore decidedly advantageous. The exudate disappears and leaves the eye perfectly normal in forty-eight hours after injection. 5. If the ophthalmo-tuberculin test proves as efficacious as the foregoing experiments seem to indicate we have in it a comparatively rapid and easy means of diagnosing tuberculosis in cattle. Such being the case the method cannot fail to come into general use superseding the present laborious method of applying the test. Cattle can be injected and then inspected sixteen to twenty-four hours afterward. There are many problems in connection with the reaction which must necessarily be studied. The following are a few of the propositions: 1. Is it possible to tell by the reaction how far the tubercular process has progressed in the body? 2. Is there any relationship between the intensity of the reaction and the number and severity of the tubercular lesions? 3. Will the test prove to be more accurate than the ordinary tuberculin test which is said to reveal all but four per cent. of the cases ? 4. Will the test reveal tuberculosis after a subcutaneous tuberculin injection? 5. Will animals react a second time if the first tuberculin is placed in the eye and the second given by the ordinary subcutaneous method and conversely? These and many more points must be thoroughly investigated before the efficiency of the test is proven. The opththalmo-tuberculin test will be repeated on other cattle, and also on the cattle used in these experiments. Experiments are being made to determine the efficiency of the cutaneous tuberculin reaction in cattle. We wish in this paper to give only the preliminary findings.
PMCID: PMC2124517  PMID: 19867128
12.  Evaluation of inadequate, indeterminate, false-negative and false-positive cases in cytological examination for breast cancer according to histological type 
Diagnostic Pathology  2012;7:53.
Background
We previously investigated the current status of breast cytology cancer screening at seven institutes in our area of southern Fukuoka Prefecture, and found some differences in diagnostic accuracy among the institutions. In the present study, we evaluated the cases involved and noted possible reasons for their original cytological classification as inadequate, indeterminate, false-negative and false-positive according to histological type.
Methods
We evaluated the histological findings in 5693 individuals who underwent cytological examination for breast cancer (including inadequate, indeterminate, false-negative and false-positive cases), to determine the most common histological types and/or features in these settings and the usefulness/limitations of cytological examination for the diagnosis of breast cancer.
Results
Among 1152 cytologically inadequate cases, histology revealed that 75/173 (43.6%) cases were benign, including mastopathy (fibrocystic disease) in 38.6%, fibroadenoma in 24.0% and papilloma in 5.3%. Ninety-five of 173 (54.9%) cases were histologically malignant, with scirrhous growing type, invasive ductal carcinoma (SIDC) being significantly more frequent (49.5%) than papillotubular growing type (Papi-tub) (P < 0.0001), solid-tubular growing type (P = 0.0001) and ductal carcinoma in situ (DCIS) (P = 0.0001). Among 458 indeterminate cases, 54/139 (38.8%) were histologically benign (mastopathy, 30.0%; fibroadenoma, 27.8%; papilloma, 26.0%) and 73/139 (52.5%) were malignant, with SIDC being the most frequent malignant tumor (37.0%). Among 52 false-negative cases, SIDC was significantly more frequent (42.3%) than DCIS (P = 0.0049) and Papi-tub (P = 0.001). There were three false-positive cases, with one each of fibroadenoma, epidermal cyst and papilloma.
Conclusions
The inadequate, indeterminate, false-negative and false-positive cases showed similar histological types, notably SIDC for malignant tumors, and mastopathy, fibroadenoma and papilloma for benign cases. We need to pay particular attention to the collection and assessment of aspirates for these histological types of breast disease. In particular, several inadequate, indeterminate and false-negative cases with samples collected by aspiration were diagnosed as SIDC. These findings should encourage the use of needle biopsy rather than aspiration when this histological type is identified on imaging. Namely, good communication between clinicians and pathological staff, and triple assessment (i.e., clinical, pathological and radiological assessment), are important for accurate diagnosis of aspiration samples.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7349809170055423
doi:10.1186/1746-1596-7-53
PMCID: PMC3502405  PMID: 22607447
Breast cytology; False-negative; False-positive; Indeterminate; Inadequate
13.  Diabetic Mastopathy as a Radiographically Occult Palpable Breast Mass 
Case Reports in Medicine  2011;2011:162350.
Diabetic mastopathy is an uncommon, benign disease of the breast that can occur in women with diabetes and clinically mimic breast cancer. We describe a patient with long-standing type 1 diabetes who presented with a palpable breast mass with negative imaging findings on mammography, ultrasonography, and breast MRI. Surgical biopsy and histopathology confirmed diabetic mastopathy. We use this case to highlight the recognition, radiographic features, pathology, and management of this benign breast condition and emphasize that, in diabetic patients, the differential diagnosis of a new breast mass should include diabetic mastopathy.
doi:10.1155/2011/162350
PMCID: PMC3216295  PMID: 22110508
14.  Axillary lymphadenopathy as a first symptom of diabetic mastopathy 
BMJ Case Reports  2009;2009:bcr03.2009.1703.
Diabetic mastopathy is an unusual fibroinflammatory breast lesion that characteristically presents in premenopausal women with long-standing type 1 diabetes mellitus.
Patients present with clinically suspicious breast masses or axillary lymph nodes with imaging characteristics indistinguishable from malignancy. Fine needle aspiration is often inadequate and a core biopsy should be performed. Excisional biopsy is not necessary, and annual follow-up is recommended. Recognition of diabetic mastopathy should lead to better care of patients with breast nodules or axillary masses who are diabetic, avoiding surgery for this benign condition.
doi:10.1136/bcr.03.2009.1703
PMCID: PMC3027411  PMID: 21686971
15.  Primary Labial Tuberculosis: A Rare Presentation 
Tuberculosis is one of the oldest scorches of mankind that has not left this world even today. The disease is more common in the developing countries. Oral tuberculosis has been considered in 0.1-5% of all tuberculous infections. Mostly, the oral tuberculous lesions are secondary to pulmonary tuberculosis, but rarely primary lesions may occur. Primary lesions occur due to direct inoculation of the microorganism into the oral mucosa and mainly seen in the young individuals. Tongue is the most common oral site involved. Of all the sites involved, labial involvement is extremely rare. This case report intends to throw light on one such unique case, where a young male patient presented with a primary tubercular lesion of the lip. The lesion resolved immediately after anti tubercular therapy.
doi:10.4103/2141-9248.126623
PMCID: PMC3952285  PMID: 24669346
Granulomatosis; Labial; Oral; Tuberculosis
16.  Breast Tuberculosis- Clinical Spectrum and Management 
The Indian Journal of Surgery  2010;72(6):433-437.
Objective of the study was to report the clinical spectrum, investigative profile and management of breast tuberculosis patients attending a tertiary care hospital. Breast tuberculosis is an uncommon form of tuberculosis. Knowledge of its varied clinical presentation and diagnostic modalities help in diagnosing this easily treatable disease. Retrospective data of 63 consecutive patients with breast tuberculosis was analyzed and information regarding demographic details, clinical presentation, cytology, histopathology and management was noted. Breast tuberculosis is essentially a disease of females (98.41%). 49.20% patients were below 30 years of age and 68.25% were from rural areas. Incidence of tubercular mastitis increases with parity (71.42% with p > 2). Commonest presentation was with painless lump (73%). Nodulocaseous tubercular disease was found in 74.60% patients whereas, 6.3% were of disseminated variety. Primary focus was detected in lungs in 11.1% patients, while 46.03% presented with loco-regional lymph nodes. FNAC was found to be a sensitive tool of diagnosis in 74.60% patients; however 25.39% cases were diagnosed with biopsy. ATT remained mainstay of treatment with surgical intervention as and when required. Breast tuberculosis despite being uncommon is not rare. Although diagnosis is not difficult but one should know where to suspect. Once confirmed treatment outcome is often rewarding.
doi:10.1007/s12262-010-0166-5
PMCID: PMC3077198  PMID: 22131650
Breast tuberculosis; Cytology; Biopsy
17.  Closing–opening wedge osteotomy for severe, rigid, thoracolumbar post-tubercular kyphosis 
European Spine Journal  2010;20(3):343-348.
Childhood spinal tuberculosis, especially when associated with severe vertebral destruction of more than two vertebral bodies can end up in severe deformity. These children show progressive deformity throughout the period of growth and can develop severe kyphosis of >100°. Such kyphosis is severely disabling with significant risk of neurological deficit and respiratory compromise. Surgical correction of these deformities by both anterior and posterior approaches has been described but each have serious limitations of approach, correctability and safety. We describe here a technique of posterior closing–anterior opening osteotomy, which allowed us to correct a rigid post-tubercular deformity of 118° in a 13-year-old boy with neglected spinal tuberculosis. The patient was a 13-year-old boy, who had contracted spinal tuberculosis at the age of 6 years. Although the disease was cured by anti-tubercular chemotherapy, he continued to deteriorate in deformity and presented to us with severe thoracolumbar kyphosis (118°). He was neurologically intact but was beginning to show shortness of breath on exertion. Patient also had fore shortening of the trunk with impingement of the rib cage on the iliac crest. Radiographs revealed complete destruction of T12, L1 and L2 vertebral bodies with the T11 vertebra fusing with L3 anteriorly. CT scans and MRI revealed severe collapse of the vertebral column and the spinal cord being stretched over the ‘internal gibbus’, which was formed by the remnants of the destroyed vertebrae. A single stage closing–opening osteotomy was done by a midline posterior approach with continuous intraoperative spinal cord monitoring. The procedure involved extensive laminectomy of T11–L2, pedicle screw fixation of three levels above and three levels below the apex, a wedge osteotomy at the apex of the deformity from both sides, anterior column reconstruction by appropriate-sized titanium cage and gradual correction of deformity by closing the posterior column using the cage as a fulcrum. This allowed us to achieve a correction to 38° (68% correction). There was no intraoperative or perioperative adverse event and patient had good functional and radiological outcome at 1-year follow-up. In this Grand Rounds case presentation, we have also discussed the aetiology and evolution of severe post-tubercular kyphosis, which is the most common cause of spinal deformity in the developing world. Early identification of children at risk for severe deformity, the time and ideal methods of prevention of such deformities are discussed. The pros and cons of the available options of surgical correction of established deformity and the merits of our surgical technique are discussed.
Electronic supplementary material
The online version of this article (doi:10.1007/s00586-010-1526-3) contains supplementary material, which is available to authorized users.
doi:10.1007/s00586-010-1526-3
PMCID: PMC3048222  PMID: 20717833
Post-tubercular; Kyphosis; Closing–opening wedge; Osteotomy
18.  Tuberculosis of the Testis: A Case Report 
A 45-year-old man visited our clinic with a painless swelling of the left scrotum and an ulcer as chief complaints. A hard and indurated mass was palpable with ulcerating foci that were proximal and distal, measuring 3 × 2 cm and 2 × 1 cm respectively and about 2 cm apart. Laboratory data were normal except for an elevated erythrocyte sedimentation rate (ESR), and white blood cell (WBC) differential showed neutropenia and lymphocytosis. A diagnosis of left testicular tumor was made and the patient had a left orchidectomy with fistulectomy. Histopathology results showed a stratified squamous epithelium with tuberculous granuloma and necrotic caseation. Patient is currently on anti-tubercular medication. The rarity of this condition makes these findings important to report.
doi:10.4137/CCRep.S9451
PMCID: PMC3528111  PMID: 23300353
left scrotal mass; tuberculosis; caseous necrosis; tuberculous granulomas
19.  Value of breast imaging in women with painful breasts: observational follow up study 
BMJ : British Medical Journal  1998;317(7171):1492-1495.
Objectives
To determine the value of breast imaging in patients with localised or diffuse pain in the breast in whom physical examination shows no abnormalities.
Design
Observational follow up study.
Setting
Radiology department of a teaching hospital in the Netherlands.
Subjects
Altogether 987 women referred for radiological breast imaging because of pain alone and a control group of 987 asymptomatic women referred for a screening mammogram.
Main outcome measures
Correlation of the radiological findings with clinical and pathological findings over two years of follow up.
Results
Radiological examination of the painful breast(s) showed the following: normal findings in 854 (86.5%) women, benign abnormalities in 85 (8.6%; mainly small cysts or mastopathy), abnormalities that were probably benign in 36 (3.6%), suspicious findings in 8 (0.8%), and malignancy in 4 (0.4%). Biopsy of the painful area was performed in 10 of the 939 women with normal findings or benign abnormalities, in two of 36 women with radiological abnormalities that were probably benign, and in all women with suspicious or malignant findings. Only the four lesions that had been classified radiologically as malignant were found to be malignant at surgery. The prevalence of breast cancer was similar in symptomatic and control women.
Conclusions
Breast imaging in women who present with pain alone is of value only in providing reassurance—no abnormalities are usually found in the painful area, radiological abnormalities classified as benign do not generally have any clinical consequences, and the prevalence of cancer is low in these women. Biopsy of the painful area should be performed only where radiological findings are suspicious.
Key messagesGeneral practitioners and hospital specialists often request a mammogram for women with localised or diffuse pain in the breast but no palpable abnormalitiesThe particular value of breast imaging in patients with breast pain alone is reassuranceBiopsy of the painful area is unnecessary where the radiological findings are not suspicious
PMCID: PMC28731  PMID: 9831579
20.  Bilateral Parotid Tuberculosis 
Tuberculosis of parotid is a rare clinical entity, and cases of bilateral tubercular parotitis are even rarer. We present a case of bilateral primary parotid tuberculosis in a 49-year-old female. The patient received anti-tuberculosis treatment for six months, resulting in complete resolution of the disease. We also review the theories related to the pathogenesis of tubercular parotitis, and propose a novel hypothesis about greater involvement of parotid gland as compared to other salivary glands in primary tuberculosis.
doi:10.4103/0974-777X.83543
PMCID: PMC3162820  PMID: 21887065
Mycobacteria; Parotid; Pathogenesis; Tuberculosis
21.  Can cytomorphology of granulomas distinguish sarcoidosis from tuberculosis? Retrospective study of endobronchial ultrasound guided transbronchial needle aspirate of 49 granulomatous lymph nodes 
CytoJournal  2013;10:19.
Background:
The differential diagnosis of tuberculosis (TB) and sarcoidosis on fine needle aspiration material is very challenging in tubercular endemic regions. We carried out a pilot study to explore cytomorphologic features of granulomas which could help in differentiation between sarcoidosis and TB. Final diagnoses in these patients were based on clinical, microbiologic and follow-up studies.
Materials and Methods:
Endobronchial ultrasound guided transbronchial needle aspiration smears of 49 consecutive patients with a final cytologic diagnosis of granulomatous lymphadenitis were reviewed. Based on cytologic features two cytologic categories were enunciated and the results were correlated with microbiologic studies and/follow-up of minimum of 6 months.
Results:
The cytologic categories did not correlate with the final clinical outcome of patients.
Conclusions:
Different patterns of granulomas observed in cytology smears do not help distinguish TB from sarcoidosis. The novel non-invasive techniques of mediastinal sampling though help in confirming granulomatous pathology, distinction between these entities and treatment decisions still depend upon correlating cytologic, microbiologic, clinical and radiological data in a large number of cases in tubercular endemic regions.
doi:10.4103/1742-6413.119008
PMCID: PMC3814850  PMID: 24228066
Endobronchial ultrasound guided transbronchial needle aspiration; granulomas; sarcoidosis; tuberculosis
22.  Pleural Tuberculosis Mimicking Inflammatory Pseudotumour 
A pseudotumour is a rare presentation of bronchopulmonary tuberculosis which occurs in immunocompetent patients, which can simulate malignancy, both clinically and radiologically, and may cause delay in its diagnosis and treatment. The incidence of bronchopulmonary pseudotumours was found to vary from 2-4%, as was seen in various studies. A mycobacterial pseudotumour of the pleura is a rare entity. We are reporting a case of a pleura based tubercular pseudotumour in a 59 years old patient who presented with a four month history of the nonspecific symptoms of cough and chest pain. The radiological investigations showed that a pleural based mass lesion was occupying the right lower hemithorax. The initial biopsy was suggestive of a hyalinizing variant of an inflammatory pseudotumour. The follow-up surgical resected mass was consistent with the features of a tubercular granuloma. The clinical presentation and the histopathological findings have been presented, with a brief review of the literature. Due to its varied and unusual presentation, bronchopulmonary tuberculosis should always be kept in mind when a patient with a similar clinical and a radiological picture is being evaluated.
doi:10.7860/JCDR/2013/4382.2888
PMCID: PMC3644451  PMID: 23730653
Tuberculosis; Malignancy; Pseudotumour; Pleura
23.  Spontaneous atraumatic fracture of a cervical vertebra in tuberculosis: a case report 
Introduction
Spontaneous pathological fractures of the cervical spine due to tuberculosis are rare. But with escalating incidences of atypical presentations of tubercular disease, clinicians should exercise a high index of suspicion for early diagnosis of such cases.
Case presentation
We present a case of a 50-year-old Hindu man from northern India, who complained of pain and stiffness in his neck. His radiographs showed a fracture in his second cervical vertebral body. But further investigations raised the suspicion of an infective pathology, which was corroborated by magnetic resonance imaging and fine needle aspiration cytology. His symptoms improved and the fracture healed following antitubercular chemotherapy and immobilization.
Conclusion
In endemic regions like India, clinicians should be on the lookout for atypical presentations of tuberculosis. Any suspicious lesion should be evaluated with care for clinical, radiological and laboratory evidences of the infection. The affected spine should be protected and appropriate chemotherapy should be instituted at the earliest opportunity.
doi:10.1186/1752-1947-6-138
PMCID: PMC3419093  PMID: 22651918
24.  Improved diagnosis of central nervous system tuberculosis by MPB64-Target PCR 
Brazilian Journal of Microbiology  2008;39(2):209-213.
Central nervous system (CNS) tuberculosis is a serious clinical problem, the treatment of which is sometimes hampered by delayed diagnosis. Clearly, prompt laboratory diagnosis is of vital importance as the spectrum of disease is wide and abnormalities of the cerebrospinal fluid (CSF) are incredibly variable. Since delayed hypersensitivity is the underlying immune response, bacterial load is very low. The conventional bacteriological methods rarely detect Mycobacterium tuberculosis in CSF and are of limited use in diagnosis of tuberculous meningitis (TBM). This double blind study was, therefore, directed to the molecular analysis of CNS tuberculosis by an in-house-developed PCR targeted for amplification of a 240bp nucleotide sequence coding for MPB64 protein specific for Mycobacterium tuberculosis. Based on the clinical criteria, 47 patients with CNS tuberculosis and a control group of 10 patients having non-tubercular lesions of the CNS were included in the study. Analyses were done in three groups; one group consisting of 27 patients of TBM, a second group of 20 patients with intracranial tuberculomas and a third group of 10 patients having nontubercular lesions of the CNS acted as control. There were no false positive results by PCR and the specificity worked out to be 100%. In the three study groups, routine CSF analysis (cells and chemistry), CSF for AFB smear and culture were negative in all cases. PCR was positive for 21/27 patients (77.7% sensitivity) of the first group of TBM patients, 6/20 patients (30% sensitivity) of the second group with intracranial tuberculomas were positive by PCR and none was PCR-positive (100% specificity) in the third group. Thus, PCR was found to be more sensitive than any other conventional method in the diagnosis of clinically suspected tubercular meningitis.
doi:10.1590/S1517-83822008000200002
PMCID: PMC3768381  PMID: 24031203
CNS tuberculosis; tuberculous meningitis (TBM); intracranial tuberculomas; PCR; Mycobacterium tuberculosis
25.  Kyphosis in spinal tuberculosis – Prevention and correction 
Indian Journal of Orthopaedics  2010;44(2):127-136.
Spinal deformity and paraplegia/quadriplegia are the most common complications of tuberculosis (TB) of spine. TB of dorsal spine almost always produces kyphosis while cervical and lumbar spine shows reversal of lordosis to begin with followed by kyphosis. kyphosis continues to increase in adults when patients are treated nonoperatively or by surgical decompression. In children, kyphosis continues to increase even after healing of the tubercular disease. The residual, healed kyphosis on a long follow-up produces painful costopelvic impingement, reduced vital capacity and eventually respiratory complications; spinal canal stenosis proximal to the kyphosis and paraplegia with healed disease, thus affecting the quality and span of life. These complications can be avoided by early diagnosis of tubercular spine lesion to heal with minimal or no kyphosis. When tubercular lesion reports with kyphosis of more than 50° or is likely to progress further, they should be undertaken for kyphus correction. The sequential steps of kyphosis correction include anterior decompression and corpectomy, posterior column shortening, posterior instrumentation, anterior bone grafting and posterior fusion. During the procedure, the spinal cord should be kept under vision so that it should not elongate. Internal kyphectomy (gibbectomy) is a preferred treatment for late onset paraplegia with severe healed kyphosis.
doi:10.4103/0019-5413.61893
PMCID: PMC2856387  PMID: 20418999
Kyphotic deformity; late onset paraplegia; TB spine; kyphus correction; extrapleural anterolateral approach

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