A 44-year-old man with hemoptysis.

A 44-year-old man with background history of diffuse cutaneous systemic sclerosis and dilated cardiomyopathy receiving immunosuppressive medications, presented with a 2-month history of cough and streaky hemoptysis. Clinicoradiological features were consistent with an endotracheal mass. Subsequently, the patient developed nodular skin lesions and the tracheal mass increased in size causing central airway obstruction. This clinicopathologic conference discusses the clinical and radiological differential diagnoses of such a clinical presentation and their management options.

PRESENTATION OF THE CASE

Raju Pangeni

A 44-year-old man presented to the pulmonary outpatient clinic with a history of a dry cough and occasional streaky hemoptysis of 2 months' duration. He had no constitutional symptoms and denied having chest pain, wheezing, orthopnea, paroxysmal nocturnal dyspnea, hoarseness, dysphagia, or bleeding tendencies. He was diagnosed with diffuse cutaneous systemic sclerosis with polyserositis and cardiomyopathy (left ventricular ejection fraction 30%) 4 years ago and had been clinically stable on treatment with oral steroids and methotrexate. Other medications included diuretics, carvedilol, and aspirin. He was a lifetime never smoker and nonalcohol consumer with no recent exposure to a patient with active tuberculosis, occupational dusts, chemicals, and to birds/pets. He had received a course of antibiotics with no clinical improvement.

On physical examination, the vital signs and oxygen saturation while breathing room air were normal. Examination revealed digital pitting scars and sclerodactyly. Respiratory system examination was unremarkable. JVP was not elevated. On cardiovascular examination, third heart sound was audible and apex beat was palpable in 6th intercostal space lateral to the midclavicular line. His blood counts, renal and liver function tests and urine examination were within normal range. Sputum samples sent for Gram stain and culture, acid-fast stain, mycobacterial cultures were negative. HIV-ELISA was negative.

Initial chest radiograph demonstrated cardiomegaly along with narrowing of lower tracheal air shadow [Figure 1a]. Computerized tomographic (CT) scan of thorax revealed an endoluminal soft-tissue mass in the distal trachea along with few left upper lobe lung nodules [Figure 1b]. With the possible clinico-radiological diagnosis of a tracheal tumor, flexible bronchoscopy was performed which showed a polypoidal growth in the distal trachea, located 2 cm above the carina and was occupying approximately one-third of the cross-sectional tracheal lumen. The distal airways appeared normal. Multiple endobronchial biopsies and wash were taken and sent for pathological analysis.

Figure 1

(a) Chest radiograph demonstrating distal tracheal narrowing. (b) Computerized tomography thorax showing tracheal endoluminal growth

The patient was lost to follow-up and presented again to the outpatient department a month later with a fresh episode of streaky hemoptysis along with the appearance of skin nodules over the scalp and right inguinal region. Clinical examination revealed the presence of expiratory stridor. He had a nodular growth over the right frontotemporal region of the scalp [Figure 2c] and another on the right medial thigh [Figure 2b], which were well-defined, exophytic with undermined base, painless, nonpruritic, nonnecrotic, and nondischarging. A repeat bronchoscopy showed that the tracheal mass had enlarged in size to occupy nearly two-third of the distal tracheal lumen [Figure 2a]. An excisional biopsy of the nodules was performed. Positron-emission tomography CT scan was also performed which showed high FDG uptake from the tracheal as well as the cutaneous lesions along with a circumferential bowel thickening in the distal small bowel. Colonoscopy was planned but deferred in view of his poor cardiac reserve.

Figure 2

(a) Bronchoscopic view showing tracheal mass obstructing a significant part of the tracheal lumen. (b and c) Cutaneous nodules over inguinal regions and the scalp

SALIENT FEATURES OF THE CASE AND DIFFERENTIAL DIAGNOSIS

Karan Madan

This middle-aged man with the previous history of systemic sclerosis and dilated cardiomyopathy, apparently well controlled on medications, has now presented with a 2-month history of cough and streaky hemoptysis. As he had a longstanding cardiac disease and was on antiplatelets, these symptoms could easily be overlooked and be attributed to heart failure and drug-induced coagulopathy. However, the lack of characteristic symptoms and signs of heart failure, history of hemoptysis, absence of bleeding manifestations elsewhere and presence of distal tracheal narrowing in the chest radiograph prompted us to do a further workup. The lack of constitutional symptoms, CT findings and bronchoscopy point toward a localized airway involvement along with possible pulmonary parenchymal disease. We would like to review the differential diagnoses of tracheal tumors in this age group.

Saurabh Mittal

Malignant tracheal tumors

Primary tracheal tumors are rare entities, accounting for < 1% of all malignant tumors.[1] Most primary tracheal tumors are malignant with squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) accounting for >90% of the cases. SCC is common in smokers whereas ACC is more prevalent in nonsmokers. Carcinoma arising from thyroid or esophagus can metastasize or infiltrate into the trachea often leading to central airway obstruction. In a nonsmoker with no history suggestive of esophageal involvement, ACC remains a possibility. Solitary tracheal carcinoid is another differential diagnosis, and these can bleed and present with hemoptysis.[2] Systemic sclerosis has also been associated with increased incidence of malignancies.[3] Rare aggressive tumors of the trachea like rhabdoid tumors presenting as central airway obstruction have also been described.[4]

Benign tracheal tumors

From the management point of view, any lesion causing airway obstruction can lead to death and should not be regarded as necessarily “benign.” Squamous papilloma is the most common benign tracheobronchial neoplasm and can be solitary or multiple. Multiple papillomas can extensively involve the airways and can lead to central airway obstruction.[5] The solitary papilloma usually occurs in adults and is related to smoking or may arise de novo, unlike “papillomatosis” which is common in children and is associated with papillomavirus infection. Tracheal papillomatosis can unusually lead to respiratory failure necessitating urgent rigid bronchoscopic airway intervention. Tracheal hamartoma may demonstrate CT features of characteristic fat density along with calcification. Lipoma and leiomyoma may have a similar appearance but do not have calcified areas. These tumors are usually slow growing. It is difficult to rule out benign neoplasms in our patient.

Infective etiologies

Tuberculosis can have varied clinical and radiological presentation depending on the bacterial and host characteristics and continues to be the major diagnostic challenge in the developing world. Inflammatory polyps may form due to chronic irritation, trauma, infection, or foreign body which seems unusual in this case considering the tracheal location of the lesion rather than bronchial. Endobronchial fungal infections due to Aspergillus, Mucor, Candida, Coccidioides, and Histoplasma species are well described in immunocompromised patients but can also occur in apparently immunocompetent individuals also.[67] I would suggest bronchoscopic samples to be processed for stain and cultures for mycobacteria and fungi in addition to histopathology.

CLINICAL DIAGNOSIS

Primary tracheal tumor (likely malignant).

GC Khilnani

With these clinical possibilities, can we have the histopathological evaluation of the specimen?

Sudheer Arava

Histopathological examination of the endobronchial biopsy from the tracheal tumor revealed sheets of histiocytes with areas of necrosis. Majority of the histiocytes showed the presence of numerous, tiny intracellular organisms. Special histochemical stain, Gomori silver methenamine stain showed that these organisms are approximately measuring about 2–4 microns and they have clear space around them. These morphological features are characteristic of Histoplasma organisms [Figure 3a and b]. Stains for acid-fast bacilli were negative. Tracheal wash from the tumor revealed mainly hemorrhagic material with few alveolar macrophages. Cultures were sterile. KOH mount and fungal culture were negative.

Figure 3

Histopathological examination of the tracheal growth showing multiple intracellular organisms on (a) H and E and (b) Grocott-Gomori methenamine silver stain

Randeep Guleria

From the dermatological perspective, what could be the clinical possibilities at this stage?

M Ramam

In a situation like this, there are two possibilities. One that the cutaneous lesions are related to the tracheal mass, and the other that they are not. The differential diagnoses for the latter situation are very broad and would include a variety of inflammatory, infective, benign, and malignant causes of cutaneous nodules. If we assume that the cutaneous and tracheal lesions are related, the nodules may represent cutaneous metastases from a primary lung malignancy, or metastases to both the skin and lung from a primary malignancy located elsewhere. Infections that could affect both the lung and the skin may present similarly. Tuberculosis is the most common such infection but the respiratory mycoses such as histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, aspergillosis, and pneumocystis also enter the differential diagnosis. Rhinosporidiosis usually affects the nose and upper respiratory tract but tracheal masses have been reported and cutaneous dissemination may also occur. In this case, the endobronchial biopsy report was available at the time the cutaneous lesions were evaluated and histoplasmosis was considered in the differential diagnosis though this is an unusual presentation.

Microscopic examination of the two excisional biopsy samples also revealed similar histopathological features like that of tracheal biopsy with sheets of histiocytes and numerous intracellular organisms morphologically resembling Histoplasma.

PATHOLOGICAL DIAGNOSIS

Disseminated Histoplasmosis–Tracheal and Cutaneous Involvement.

Anant Mohan

Histoplasmosis is caused by inhalation of spores from a dimorphic fungus, Histoplasma capsulatum. The fungus remains in a mycelial form at ambient temperatures and grows as yeast at body temperature in humans.[8] The disease is endemic along the river valleys of the United States and Yangtze River in China. In India, it is endemic in the Gangetic delta and has also been reported from eastern, northeastern and southern India. It may present in several forms predominantly pulmonary manifestations (pulmonary syndrome), mediastinal symptoms (mediastinal syndrome), or with features of dissemination to other organs such as colon, adrenals, skin, and brain (progressive disseminated histoplasmosis). It has also been described as a causative agent for fibrosing mediastinitis and tracheobronchial stenosis.[9] Disseminated histoplasmosis presenting as diffuse tracheal nodularity and ulcerative growths has been described in some case reports.[10] To the best of our knowledge, histoplasmosis presenting as well-defined cutaneous nodules and isolated tracheal mass has not been reported previously in the literature.

Vijay Hadda

Most patients with pulmonary histoplasmosis have nonspecific radiological findings. These range from airspace opacities or consolidation in acute cases with or without mediastinal lymphadenopathy to single or diffusely calcific nodules in chronic form. Thoracic CT is helpful in the evaluation of patients with central airway obstruction and those with suspected fibrosing mediastinitis. The distal tracheal growth along with the lung nodules and cutaneous lesions suggests disseminated form of histoplasmosis. Bronchoscopic findings also are nonspecific and similar to any infective or neoplastic conditions and include nodular, ulcerative growths with exudative or erythematous mucosa.

FINAL DIAGNOSIS

Disseminated histoplasmosis, diffuse cutaneous systemic sclerosis, and dilated cardiomyopathy.

How was this patient managed?

This patient, on the one hand, had critical airway narrowing which could be fatal if the obstruction worsens. Rigid bronchoscopy is the ideal modality for airway management and recanalization in this situation.[5111213] However, the multiple underlying comorbidities in the patient, especially the presence of dilated cardiomyopathy increase the risk of general anaesthesia and procedural complications during rigid bronchoscopy. Unlike malignant central airway obstruction, where the nature of disease usually leads to consideration of rigid bronchoscopy and airway stenting as the modality of choice, in this patient the infectious etiology as the underlying cause also merits considering the option of a conservative approach.

We discussed the options along with the associated risks and benefits with the patient and the caregivers. The patient was admitted to the hospital, and antifungal treatment was initiated. It was decided to keep the patient under close monitoring and proceed to rigid bronchoscopy if the airway obstruction worsened. Intravenous liposomal amphotericin B was started. The patient showed quick improvement of symptoms over the next few days and after a cumulative dose of 4 g of amphotericin B, stridor disappeared, and the tracheal mass significantly decreased in size [Figure 4]. The patient was discharged home on oral Itraconazole 200 mg twice daily and was planned to continue it for at least a year after complete resolution of the sites of involvement. Methotrexate was discontinued, and prednisolone was gradually tapered off, as advised by the rheumatology services.

Figure 4

Follow-up of bronchoscopic image showing reduction in size of the tracheal mass after treatment with intravenous Amphotericin

SUMMARY

This case highlights that tracheal masses have a broad differential diagnosis and are not always malignant. Histoplasmosis can present with an isolated tracheal growth causing central airway obstruction, which may respond well to systemic antifungals and invasive bronchoscopic interventions may be considered judiciously. One must also keep in mind the atypical presentations of fungal infections, especially in immunosuppressed patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.