Invasive mucinous adenocarcinoma with lepidic-predominant pattern coexisted with tuberculosis: a case report

Abstract

We observed a rare case of invasive mucinous adenocarcinoma (IMA) with a lepidic-predominant pattern accompanied by pulmonary tuberculosis. An 85-year-old man with repeated cough and sputum was admitted to Xinhua Hospital. T-SPOT test result was 212 pg/ml (reference value of negative is<14 pg/ml), Mycobacterium tuberculosis culture was positive, and tuberculin skin test (PPD) was negative (skin induration<5 mm). The patient was treated with several courses of antibiotics and anti-tuberculosis treatments. Repeated chest CT scans showed disease progression. Bronchoscopy yielded negative results. PET-CT scans showed negative results. A percutaneous lung biopsy revealed mucin-secreting cells lining the alveolar walls. IMA with a lepidic-predominant pattern was diagnosed after invasiveness was found after experimental treatments. Simultaneous occurrence of pulmonary tuberculosis and lung cancer are common; however, the present case of IMA having a lepidic-predominant pattern and coexisting with active tuberculosis has not been reported yet.

Keywords

invasive mucinous adenocarcinoma / lepidic-predominant / tuberculosis

Introduction

Invasive mucinous adenocarcinoma (IMA) is a new category of lung adenocarcinoma characterized by well-differentiated cellular features with scattered tumor cells in large mucin pools that grow along alveolar walls [¹].

The diversity of clinical manifestations and image performances complicate the diagnosis of IMA, especially with a lepidic-predominant growth pattern, which refers to the tumor progress along the alveolar wall and causing no parenchymal damage. Tuberculosis is a common disease that can cause sustained inflammation and leads to fibrosis, scarring, and bronchiectasia. Moreover, this disease shares the same symptoms with IMA [²]. Lung adenocarcinoma and tuberculosis comorbidity is a clinical problem that is rare; moreover, it presents a challenge for diagnosing and treating both diseases [³,⁴]. In this study, we describe a case of IMA with lepidic-predominant pattern accompanied by active tuberculosis, and discuss the potential correlation between them.

Presentation of case

An 85-year-old man was referred to Xinhua Hospital with complaints of repeated cough and phlegm production for nearly a month. He indicated no fever, chest pain, joint pain, muscle pain, dyspnea, night sweats, skin rash, mouth ulcers, dry eyes, and weight loss. The patient has a history of tuberculosis with non-standard anti-tuberculosis treatment (Rimifon). Medical examination indicated that all vital signs were within normal range. The both lungs were clear upon auscultation, with scattered crackles in the right lung, no wheezes, rales, or rhonchi. The examination of other organs did not yield any findings of interest.

Pertinent laboratory findings included: (1) Mycobacterium tuberculosis culture was positive in the sputum specimens, (2) T-SPOT test result was 212 pg/ml (reference value of negative is<14 pg/ml), and (3) tuberculin skin test (PPD) was negative (skin induration<5 mm). Screening tests, such as repeated sputum cytology, did not find tumor cells. The amount of CA242 was 47.43 U/ml (reference value is 0–20 U/ml) and CA199 was 25 U/ml (reference value is 0–39 U/ml). The erythrocyte sedimentation rate, carcinoembryonic antigen (CEA), and neuron-specific enolase levels in the blood were normal. The chest CT scans performed on August 30, 2014 showed patchy consolidations with multiple fibrosis lesions in the bilateral pulmonary and cavernous foci in the lower lobe of the right lung (Fig. 1A).

Upon admission (August 30, 2014), the patient was treated with a combination of antibiotics, ofloxacin, and aztreonam for approximately six weeks. Chest CT scans on October 13, 2014 following treatment demonstrated the persistence of the consolidation (Fig. 1B). Sputum culture was repeated and two strains of fungi (Candida albicans and Candida glabrata) were isolated. Anti-fungal treatment of tazocin combined with voriconazole was administered for nearly 10 days. Despite these treatments, no improvements were observed in the chest images (Fig. 1C) obtained on October 24, 2014. A bronchoscopy performed in November 2014 found stenosis in the basal and dorsal segments of the lower right lobe. Then, PET-CT was performed in December 2014 (Fig. 2). Moreover, the repeat bronchoscopy was inconclusive.

M. tuberculosis was positive in the sputum and T-SPOT test result; thus, a diagnosis of TB recurrence was suspected. Anti-tuberculosis therapy was administered for two weeks, but the chest CT images on January 15, 2015 showed signs of continuing deterioration (Fig. 1D). The images showed diffuse opaque lesions along the alveolar walls in the lower right lobe, and several part-solid nodules in the lower left lobe indicated some adenocarcinoma features. Percutaneous lung biopsy on February 10, 2015 showed mucin-secreting cells lining the alveolar walls with lepidic growth (Fig. 3). Molecular data indicated negative results for the EGFR mutations. Immunohistochemical results were as follows: I15–739: TTF1(−), CK7(+), CK20(−), VILLIIN(−), CEA(+), CDX2(+), IV-collagen (+), and KI67 (+30%). This result led to a diagnosis of “invasive mucinous adenocarcinoma with lepidic-predominant pattern.” Thereafter, an experimental EGFR-TKI therapy was administered for a month. CT scans were performed on March 4, 2015 and showed signs of tumor invasion and metastasis (Fig. 1E). The patient was discharged without successful treatment or alleviation of symptoms.

Discussion

An interesting expression associated with this patient is the lepidic-predominant pattern, which is characterized by tumor cells that grow along pre-existing alveolar structures without destroying the lung parenchyma. Various presentations and the wide spectrum of imaging patterns [¹], which present the pattern either as a solitary pulmonary nodule or a mass, consolidation, and multifocal disease [⁵,⁶], render the pattern difficult to distinguish from pneumonia, tuberculosis, bronchiectasis, and other pulmonary infections [⁷]. Even in PET-CT, the pattern is often misdiagnosed as an inflammatory change [⁸].

The differential diagnosis of active tuberculosis and adenocarcinoma is important but difficult. The manifestations of this case are complicated and misleading. On the one hand, the patient had suffered from recurrent lung infections for a prolonged period without symptom relief after anti-inflammatory treatments. The CT scans indicated disease progression. CA242 was 47.43 U/ml (reference value is 0–20 U/ml); thus, a diagnosis of tumor was suspected. However, bronchoscopy and PET/CT yielded negative results, which disproved our hypothesis. On the other hand, considering that M. tuberculosis was positive in the sputum and the T-SPOT test result was 212 pg/ml (reference value of negative is<14 pg/ml) in addition to the patient’s history of pulmonary tuberculosis, a diagnosis of recurrent tuberculosis was suspected. Moreover, the patient showed no relief of symptoms even after anti-tuberculosis therapy, which again hindered our diagnostic process. Finally, this case was diagnosed by percutaneous lung biopsy as IMA with a lepidic-predominant pattern, a case that has not been reported yet.

Pulmonary tuberculosis and adenocarcinoma rarely occur simultaneously, but have been proven to be linked [⁹]. Pulmonary tuberculosis patients have an increased lung cancer risk [¹⁰], considering that tuberculosis may cause sustained inflammation that lead to fibrosis and host-tissue damage [⁹]. As a result, carcinogen deposition in the area is enhanced [⁴], and tuberculosis mycobacterial cell wall components may induce nitric oxide production and reactive oxygen species, both implicated in carcinogenesis [¹¹]. Another study suggested that carcinoma may cause reactivate tuberculosis [¹²]. We were unable to determine the disease chronology in this patient. However, in all the cases we have studied, none of the tumor cells have specifically addressed the same growth pattern as in this patient. The growth pattern observed in the patient led to a high degree of misdiagnosis of the tumor, especially when combined with other pulmonary infectious diseases, such as tuberculosis. In this case study, we reported this study to alert clinicians to the co-occurrence of tuberculosis and tumor in this growth pattern. Moreover, the diagnosis of this disease is a reminder of the diversity of imaging changes in this tumor. As such, a combination of different methods for pathology diagnosis is necessary. Our case indicated the possible link between pulmonary tuberculosis and lepidic growth pattern [¹³,¹⁴], which remains to be studied.

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