Tuberculosis mimicking cancer—A reminder

Tuberculosis Mimicking Cancer-A

SILVIO

D. PITLIK,

M.D.*

VICTOR

FAINSTEIN,

M.D.

GERALD

P. BODEY,

M.D.

Houston, Texas

From the Section of Infectious Diseases, Division of Medical Services, University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas. Requests for reprints should be addressed to Dr. Victor Fainstein, Infectious Disease, Box 47, M. D. Anderson Hospital, 6723 Bertner Avenue, Houston, Texas 77030. Manuscript accepted October 27, 1963. * Current address: Department of Medicine, Beilinson Hospital, Petah Tikva, Israel.

A continuing medical education quiz on this article (one hour of Category 1 credit) appears on page Al29 of this issue.

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Reminder

The charts of 26 patients who were referred with a presumptive diagnosis of neoplasms and who were ultimately found to have only tuberculosis were reviewed. Twenty-one patients (61 percent) were born in the United States, and only three patients had a history of exposure to tuberculosis. Most patients had few symptoms, and the average duration of symptoms was 2.6 f 1.5 months. Classic symptoms of tuberculosis, like fever, hemoptysis, and weight loss, were uncommon. Chest roentgenographic abnormalities were present in 62 percent of the patients. Although some of the patients had undergone nondiagnostic biopsy procedures before referral, none had had skin tests for tuberculosis. Underlying conditions were found in eight patients, and alcoholism was the most common. Laboratory abnormalities were rare with the exception of increased platelet counts, which were found in eight patients. The most common form of tuberculosis was pulmonary (14 patients) followed by lymphadenitis (nine patients). Tuberculosis remains an elusive disease even in countries with advanced medical technology. In some cases, its presentation may suggest the presence of malignancy. Tuberculosis is a protean disease that can resemble other pathologic conditions [ 1,2]. Its diagnosis is frequently delayed [3,4], especially in areas of the world with a low prevalence of infection [5,6]. Before the 19th century, tuberculosis and cancer were considered a single disease [7]. The previously interchangeable use of the word “tubercle” for either cancer or tuberculosis [7] clearly demonstrates this diagnostic confusion. We have reviewed the medical literature of the last decade and found that the issue of tuberculosis misdiagnosed as cancer has generally been documented by isolated case reports [8-261. In the last IO years, 26 patients with tuberculosis were referred to our institution with a presumptive diagnosis of malignant disease. We report on the spectrum of disease in these patients, who had active tuberculosis masquerading as cancer. PATIENTS AND METHODS The University of Texas M. D. Anderson Hospital and Tumor Institute is a referral center for patients with presumed or proved malignant diseases. We reviewed the records of patients who had Mycobacterium tuberculosis isolated from culture specimens submittedto the clinical microbiology laboratory from 1973 to 1982. During that period of time, more than 70,000 patients were admitted to our institutionand more than 50 patients were found to have tuberculosis in association with neoplasms. The records of patients with microbiologically proved tuberculosis were reviewed and those who had no

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evidence of cancer were included in this report. The microbiologic and histologic diagnoses of tuberculosis were made by routine procedures [ 271.

moptysis (two), and a mass in the breast (two). Odynophagia, dysphagia, chest pain, and skin lesions were present in one patient each. The mean length of symptoms before hospital admission was 2.8 f 1.5 months. Only three patients had a history of exposure to tuberculosis. One of them was a nurse who took care of patients with tuberculosis, and in two patients, there was a family history of this disease. Underlying conditions were found only in eight patients. Seven were alcoholic, four had chronic obstructive pulmonary disease, two were diabetic, and one had undergone gastrectomy. The initial and final diagnoses in the 26 patients, as well as the radiologic, bacteriologic, and skin testing results, are shown in Table I. The most frequent diagnosis on admission was lung cancer (11 patients, 42 percent), followed by lymphoma (six patients, 23 percent), nasopharyngeal carcinoma (three patients, 12 percent), and breast cancer (two patients, 8 percent). A diagnosis of thyroid or esophageal carcinoma and bone or liver metastasis was suspected, each in one

RESULTS

During the lo-year period, 26 patients had bacteriologically proved tuberculosis and no evidence of malignancy. The total number of patients seen during this period of time was equally divided per year. The mean age was 54 f 20 years, and the age range was 15 to 85 years. There were 14 males and 12 females. Twenty-one patients were born in the United States, four in Latin-American countries, and one in Asia. Twenty patients were Caucasian, five were black, and one was Oriental. Four patients were asymptomatic. The remaining 22 presented with few symptoms. The mean number of symptoms in those patients was 2.4. The most common symptoms were cough (10 patients), followed by anorexia (eight), cervical mass (seven), and weight loss (seven). Less common symptoms were dyspnea (five), night sweats (four), fever (three), he-

TABLE

I

Clinical, Radiographic, and Bacteriologic Findings PPD-!YJ

Patient Number

Initial Diagnosis Lymphoma Lung carcinoma Breast carcinoma Lung carcinoma Thyroid carcinoma Breast carcinoma Lymphoma Lung carcinoma

9 10

Lung carcinoma Hepatic metastasis

11

Nasopharyngeal carcinoma Bone metastasis Lymphoma Lung carcinoma Lung carcinoma

12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

Lymphoma Esophageal carcinoma Lymphoma Lung carcinoma Lung carcinoma Lung carcinoma Lymphoma Lung carcinoma Lung carcinoma Nasopharyngeal carcinoma Nasopharyngeal carcinoma

Chest Roentgenographic Findings No infiltrate Pleural effusion No infiltrate “Coin lesion” RUL No infiltrate No infiltrate Right hilar mass ML infiltrate, pleural effusion ML infiltrates, cavitation Pleural effusion

Tuberculin Teal Results -

(mm) ND 12 ND ND 15 ND 15 ND 0 ND

Isolation Site of M. Tuberculosis

Final Diagnosis

Lymph node Pleural fluid Lymph node Sputum Breast Breast Lymph node Sputum

Tuberculous lymphadenitis Pulmonary tuberculosis Tuberculous mastitis Pulmonary tuberculosis Tuberculous mastitis Tuberculous mastitis Tuberculous lymphadenitis Pulmonary tuberculosis

Sputum Sputum, pleural fluid Sputum, urine

Pulmonary tuberculosis Miliary tuberculosis

No infiltrate No infiltrate RUL infiltrate RUL infiltrate, pleural effusion No infiltrate ML infiltrates No infiltrate ML infiltrates LUL infiltrate RUL infiltrate RML infiltrate RLL infiltrate RUL infiltrate No infiltrate

ND ND 0 ND

Bone Lymph node Sputum Sputum

Pharyngeal, pulmonary, and tuberculosis Potts disease Tuberculous lymphadenitis Pulmonary tuberculosis Pulmonary tuberculosis

ND ND 22 ND 0 ND 20 ND ND ND

Lymph node Sputum Lymph node Sputum Sputum Sputum Sputum Lung Sputum Lymph node

Tuberculous lymphadenitis Pulmonary tuberculosis Tuberculous lymphadenitis Pulmonary tuberculosis Pulmonary tuberculosis Pulmonary tuberculosis Pulmonary tuberculosis Pulmonary tuberculosis Pulmonary tuberculosis Tuberculous lymphadenitis

No infiltrate

ND

Lymph node

Tuberculous lymphadenitis

ML infiltrates

15

I

ND = not done: RUL = right upper lobe; ML = multiple lobes; LUL = left upper lobe: RML = right middle lobe: RLL = right lower lobe.

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patient. In four patients, biopsy specimens were taken before their referral to our institution (lymph nodes in three patients and breast in one patient). None of these specimens was submitted for microbiologic studies, and pathologic results were inconclusive. Ten patients had normal findings on chest roentgenography. This group included seven patients with tuberculous lymphadenitis, two patients with tuberculous mastitis, and one patient with tuberculous spondylitis. The most common abnormality on chest roentgenography among the other 16 patients was multilobar infiltrations (six), followed by right upper lobe infiltrates (five), and pleural effusions (four). Infiltrates in the right middle lobe and upper left lobe were observed each in one patient. One of these patients also had a hilar mass. Cavitation was seen in only one patient, and a “coin” lesion was found in another. No abnormal roentgenographic result was interpreted outside the hospital as indicating tuberculosis. None of the 26 patients was subjected to a PPD skin test before admission. At our institution, skin testing for tuberculosis was performed in only nine patients (Table I). Six patients had induration of greater than IO mm, and three patients had no induration. M. tuberculosis was cultured from only one site in 24 patients and from two different sites in the remaining two. The most frequent site of isolation was the sputum (13 patients). Two of these specimens were obtained by bronchoscopy. The organism was isolated from lymph node biopsy specimens in nine patients and from breast, bone, and lung biopsy specimens in one patient each. M. tuberculosis was cultured from pleural fluid of two patients and from urine of one patient. Acid-fast smears of sputum showed positive findings in only three patients who had positive culture results. Acid-fast bacilli were seen on microscopic examination of five lymph node biopsy specimens and in none of the biopsy specimens obtained from other sites. The final sites of infection were the lungs in 14 patients, lymph nodes in nine, breast in two, and kidney, spine, and salivary gland in one each. Laboratory abnormalities were found in only nine patients. A decreased hemoglobin level (below 10 g/dl) was observed in only one patient. Eight patients had a platelet count greater than 4.5 X 106/mm3, and two patients had a white blood cell count greater than 10 X 104/mm3. Three patients had elevated alkaline phosphatase levels (above 110 units). On admission to our hospital, the possibility of tuberculosis was entertained in 17 patients (62 percent). The average time elapsed from admission until diagnosis of tuberculosis was 12 days and ranged from two to 60 days. None of the patients received antineoplastic chemotherapy or radiation therapy during this time. All patients except one began antituberculosis therapy at our institution and were subsequently followed by their referring physicians.

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COMMENTS Tuberculosis and cancer have been confused and easily misdiagnosed for centuries [7]. Moreover, the association of these two diseases has been recognized for many years [28-301. Despite major improvements in methods of diagnosis, tuberculosis continues to be an elusive disease [5,6]. Paradoxically, in countries with advanced medical technology, the diagnosis of tuberculosis is frequently missed [ 1,2,30]. Occasionally, it is discovered only at autopsy [5,6]. The capability of tuberculosis to mimic cancer has been documented in several isolated case reports [8-261. Most of these reports deal with uncommon forms of extrapulmonary tuberculosis involving the head and neck [8-l I], breast [12,13], gastrointestinal tract [14-181, central nervous system [ 19,201, lymph nodes [ 21,221, or urogenital tract [23-261. Interestingly, when dealing with the most common form of tuberculosis, i.e., pulmonary tuberculosis, more emphasis has been placed on its association with lung carcinoma than on the difficulty in the differential diagnosis [31,32]. Prytz and Hansen [33], however, reported on a large series of patients who underwent thoracotomy for presumed lung cancer but were found to have tuberculosis. Although operative mortality was low, they found a decreased survival rate 10 years after surgery. In clinicians’ minds, especially in countries with low incidence of tuberculosis, the possibility of mycobacterial infection is usually raised in the setting of prolonged febrile illnesses occurring in presumably predisposed groups. Epidemiologically, it is of interest that among our patients, the majority were American-born and had no history of exposure to tuberculosis or foreign travel. In contrast to previously described patients in whom the diagnosis of tuberculosis was delayed until autopsy, most of our patients were afebrile, had few symptoms, and had short-lived disease. Classic symptoms of tuberculosis like anorexia, weight loss, and hemoptysis were uncommon. Interestingly, no roentgenographic abnormalities related to tuberculosis could be recorded in 38 percent of the patients. Laboratory abnormalities, as expected in patients with chronic granulomatous infection, were unusual. However, elevated platelet counts were seen in almost one third of the patients. Worthy of mention is the fact that skin tests for tuberculosis were not performed in any of the patients before admission. The diagnosis of tuberculosis was established in most of the patients with relatively simple procedures. An earlier diagnosis could have avoided the patients’ anxiety related to the erroneous diagnosis of neoplasms and could have decreased the expense of complicated workups. Physicians must be aware of the possibility that this disease may mimic many other disease entities, especially cancer, and institute the appropriate diagnostic tests.

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