—  SPECIALTY CONFERENCE  —

Infectious Disease Pathology

Case 4 - Tuberculosis (confirmed by microbial culture)

Andre Moriera
New York University
New York, New York


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Clinical History:
The patient is a 34 year-old woman from Central America, who presented to the hospital with mental alterations.


Case 4 - Figure A
Case 4 - Figure B


Case 4 - Figure C
Case 4 - Figure D - Acid-fast stain

The clinical history was collected from her husband who accompanied her to the hospital. He says that the patient had recently immigrated to New York City area and was previously in good health. Two weeks before, the patient complained of mild headaches. The husband noted that the patient was becoming increasingly forgetful and that she started to sleep more than usual. The day he decided to bring her to the hospital she could not be easily awakened. He denies fever or convulsions. He says the patient has been losing weight slowly but does not know how much. He also says that he is not aware of any significant family history for carcinoma or other diseases. He denies alcohol and tobacco abuse.

Laboratories tests were non-contributory. She had normochromic-normocytic anemia and slight leukocytosis. A computerized tomography (CT) scan of the head showed intracranial masses suggestive of metastasis. Subsequent CT scan of the abdomen and pelvis showed a 12 cm cystic septate mass in the pelvis, posterolateral to the uterus, suggestive of a cystic adnexal neoplasm. There was no associated lymphadenopathy and intra-abdominal organs were within normal limits. A chest X-ray showed two nodules in the lung.

A transvaginal aspiration biopsy of the pelvic mass was performed.

Cytologic Findings:
The aspirated biopsy material was composed of necrotic debris and neutrophils, in the absence of epithelioid histiocytes and giant cells. Ziehl-Neelsen stains revealed acid-fast bacilli.

Diagnosis: Tuberculosis (confirmed by microbial culture)

Discussion:
Tuberculosis is the worldwide leading cause of death as the result of a single infectious agent, with an estimated 10 million new cases and 2 million deaths each year.1  Although commonly regarded as an ongoing health problem in developing countries and in immunosuppressed individuals, tuberculosis can affect all sections of the population. Several factors have been attributed to an increase in the number of cases reported in the United States in the last two decades, namely concomitant HIV infection and increased immigration from countries where tuberculosis is endemic.

Tuberculosis continues to be an important public health problem worldwide despite efforts at eradication and control. In the US, the downward trend in the incidence of new tuberculosis cases was reversed in 1985, with an increase in reported cases. The increases have been significant in racial and ethnic minorities, in immigrants, and in children younger than 15 years old. In 1993, 29.6% of people infected with M. tuberculosis were born outside of the US, compared with 22% in 1986.1 

In addition, changes have occurred not only in the demographic distribution of tuberculosis cases, but also in the anatomic distribution of disease. The number of pulmonary cases had decreased from 1963 to 1986 by an annual average of 5%; the number of extra-pulmonary cases of tuberculosis had declined only by 0.9% annually.12  In analysis of reported cases of tuberculosis in 1986, 17.5% of all tuberculosis cases were extrapulmonary. Of those, 71.2% occurred in racial/ethnic minorities and people who were not born in the US. In a different study,13  where cases were analyzed according to HIV status, 60% of HIV positive patients with pulmonary tuberculosis, also had extrapulmonary disease; 26% of HIV positive patients had extrapulmonary disease only. In HIV negative patients with pulmonary tuberculosis, 28% also had extrapulmonary disease, and 28% had only extrapulmonary disease.

One of the key components in eradication of tuberculosis is timely diagnosis. This facilitates early treatment, as well as prophylaxis for exposed social and household contacts. The diagnosis of pulmonary lesions is relatively uncomplicated, regardless of HIV status. When a biopsy is recommended, the finding of pulmonary necrotizing granulomatous inflammation with acid-fast bacilli confirms the diagnosis. In cases of extra-pulmonary tuberculosis, the diagnosis can be difficult since tuberculosis may have not been considered in the differential diagnosis. But if necrotizing granulomas are identified in a biopsy specimen, the search for acid-fast bacilli will be initiated.

Diagnostic difficulty is encountered when extrapulmonary tuberculosis mimics neoplastic processes clinically and radiographically,2-5  and a biopsy of the mass does not show the classical findings of M. tuberculosis infection, such as necrotizing granulomas. The combination of atypical presentation and atypical findings on biopsy of an immunocompetent patient may lead to misdiagnosis and delay in treatment, such as exemplified in the case presented here.

The aspirated biopsy material represented a diagnostic challenge in this case because necrotic debris and neutrophils, in the absence of epithelioid histiocytes and giant cells, mislead the cytopathologist into making the diagnosis of an abscess or necrosis of tumor. Although cases of tuberculosis presenting as suppurative inflammation have been described, these are favored to occur in the setting of severe immunodeficiency 6,7 or in the course of tuberculous lymphadenitis.8,9 

A careful search of the medical literature showed that a few cases of atypical presentations of extra-pulmonary tuberculosis have been described but only in one case 3 the disease manifested as suppurative inflammation in a solid organ (liver).

Another pitfall in these cases is the presence of atypical cells on the smears. These atypical cells are large cells with vacuolated cytoplasm, enlarged irregular nuclei and prominent nucleoli. Some resembled signet-ring cells with a distended cytoplasmic vacuole, which causes indentation of the nucleus. Immunostains on sections of cells block demonstrates reactivity to CD68, a monocytic marker in these atypical cells. Reactive macrophages have been described in cytological and histological preparation to mimic neoplastic cells.9-11 

The case presented herein underscore the importance of having a high index of suspicion for tuberculosis in certain patient groups (i.e. immigrants), even in patients who are HIV negative or whose clinical diagnosis is carcinoma. A search for acid-fast bacilli should be included in the investigation of all masses where aspiration biopsy yields necrotic debris with neutrophils to avoid unnecessary and inappropriate diagnostic and therapeutic procedures.

References

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