Case Report: Tracheal infiltration with wheezing revealing Hodgkin's disease

Version Changes

Revised. Amendments from Version 1

We are delighted to submit this new version of our case report according to the second reviewer’s comments.  We have made every attempt to fully address his comments in the revised manuscript. As mentioned, we agree that the extra-ganglionar Hodgkin lymphoma is not rare. However, the initial tracheobronchial involvement is uncommon. It does not exceed (4%) in antemortem series. We highlighted in this revised version that the diagnosis is so challenging giving that the symptoms are not specific and may mimic a wide spectrum of diseases such as (Asthma,COPD …) resulting in a diagnosis delay.In fact, most of the cases are discovered in autopsy series or during the follow up. Moreover, we have included many skilled specialists in clinical Haematology and Histopathology according to the second reviewer’s request. We do believe that his insightful suggestions impoved our manuscript. Indeed, his advice about a thorough revision of the format, the structure and the style were helpful. As suggested, our case report has been approved by a native speaker.     However, we did not change the author list, the content, nor the list of figures and tables. Below, we have outlined how we handled each of the second reviewer’s comments.

Abstract

Hodgkin's disease with an initial tracheobronchial involvement is not common. The symptoms might be misleading, resulting in a diagnosis delay. We report the case of a 38-year-old woman with a one-month history of wheezing associated with a dry cough. The physical examination revealed a good general state of health, bilateral wheezing and supra-clavicular lymphadenopathy. The adenopathy biopsy's histopathology revealed Hodgkin lymphoma. The whole body FDG-PET scan was an important tool to assess the diagnosis as well as for the staging. The patient was treated with chemotherapy. Another unusual aspect is the tracheobronchial metastasis confirmed by a bronchial biopsy. Thus, our patient was put on a second-line chemotherapy. She died one year after the initial diagnosis. To conclude, it is an atypical clinical presentation of an Hodgkin lymphoma with a tracheobronchial relapse. It should be considered in the differential diagnosis of asthma or a tracheal tumor.

Background

Hodgkin lymphoma is a malignant neoplasia arising typically from lymph nodes. An extranodal lymphoma with an initial tracheobronchial involvement is uncommon in antemortem series. It was reported in about (3.6%) of cases in literature. ¹ The symptoms are not specific and may mimic a wide spectrum of diseases like asthma or chronic obstructive pulmonary disease (COPD) … resulting in a diagnosis and a treatment delay. ^{1 , 2} It is now recognised as a treatable neoplasia. Thus, it is worth mentioning these challenges for clinicians especially after the recent therapeutic progress in order to highlight the atypical manifestations of extranodal lymphoma and to improve the management of these patients. We report the case of a 38-year-old woman with a one-month history of chest wheezing and a dry cough who did not respond to bronchodilators revealing the disease.

Case presentation

A 38-year-old woman presented to our department of Pneumology with a one-month history of dry cough and chest wheezing. She had never smoked. She has not any comorbidities or allergies. She has not a significant family history of neoplasia. She is a house-wife. She is Caucasian. She has often visited the emergency department in the last month for persistent chest wheezing. She had been given beta2-mimetics, without any clinical improvement. The physical examination at admission revealed a good general state. We noticed bilateral diffuse wheezing. Oxygen saturation was (98%) on room air. The examination of the ganglionar areas detected peripheral, bilateral, fixed supra-clavicular lymphadenopathy measuring about (2 cm of diameter). There was not an hepatosplenomegaly. The neurological examination was normal.

The chest X-ray showed a retractile opacity in the right chest with an hilar enlargement ( Figure 1).

Figure 1. Chest X-ray showing a retractile opacity in the right chest with hilar enlargement.

The body computed tomography (CT) scan revealed a bulky mediastino-hilar tumor in the right chest, measuring (90 × 85 × 71 mm), invading the right main bronchus, extending to the vena cava and infiltrating the pericardium with a subpleural right node as shown in Figures 2 and 3. Bronchoscopy showed a polypoid mass located in the carina, involving the right main bronchus. Cytology revealed malignant cells. Histopathology of the bronchial biopsy did not show any malignant lesions. Furthermore, we performed a biopsy of the supra-clavicular adenopathy. Histopathology revealed an intense staining for CD15 and CD30 with large multinuclear reed Sternberg cells. Therefore, the diagnosis of an Hodgkin lymphoma was confirmed.

Figure 2. Coronal section of the computed tomography chest demonstrating a bulky tumor invading the carina, the right main bronchus, the pericardium with a subpleural right node.

Figure 3. CT mediastinal section showing an important mediastino-hilar mass infiltrating the right main bronchus.

The 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed many sites of activity of the disease, with a high metabolic fixation of the FDG in the lymph node stations (1L,3,5,6,7,8,9,10,11R) as well as subphrenic adenopathy. Besides, it revealed an intense endotracheal metabolic fixation ( Figures 4, 5). Moreover, the bone marrow biopsy was negative. So, the diagnosis of an advanced stage Hodgkin lymphoma (stage IV) was made.

Figure 4. A PET scan image showing hypermetabolic lymph nodes.

Figure 5. A PET scan image showing the subphrenic ganglionar fixation of the FDG.

So, the patient received 4 courses of a combined BEACOPP chemotherapy protocol (Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone), as detailed in the table below ( Table 1).

Table 1. The combined BEACOPP chemotherapy protocol (21 days).

Day	Drug	Dose	Route
Day 1	Adriamycin	35 mg/m 2	IV bolus
Day 1	Mesna	1000 mg/m 2 (prior to cyclophosphamide)	IV infusion
Day 1	Cyclophosphamide	1250 mg/m 2	IV infusion
Day 1	Mesna	1000 mg/m 2 (4 hours after cyclophosphamide)	IV infusion
Day 1 - Day 3	Etoposide	200 mg/m 2	IV infusion
Day 1 - Day 7	Procarbazine	100 mg/m 2	Orally
Day 1 - Day 7	Prednisolone	40 mg/m 2	Orally
Day 8	Vincristine	1.4 mg/m 2	IV infusion
Day 8	Bleomycin	10 mg/m 2	IV infusion
Day 9 - Day 13	G-CSF	5 μg/kg	SC

IV: intravenous, SC: subcutaneous.

She was readmitted in our department 2 months because of an acute respiratory failure associated with chest wheezing. Bronchoscopy revealed a bulky stenosing polypoid mass, measuring about 3 cm of diameter, rising from the carina extending to the trachea and to the main bronchus that remains partially patent. Histopathology revealed large cells associated with an inflammatory granuloma of (lymphocytes, eosinophils, neutrophils …) and a positive staining for CD 15 and CD 30. Thus, we concluded to a tumoral progression with an endotracheobronchial relapse.

The decision of the multidisciplinary medical team was to put the patient on a second-line chemotherapy: IGEV regimen as a salvage therapy (Ifosfamide, Gemcitabine, Vinorelbine and Methylprednisolone). Moreover, injected Chest CT scan revealed a segmental pulmonary embolism. So, she had received a curative anticoagulant treatment. Unfortunately, she died one year after the initial diagnosis.

Discussion

It is well known that Hodgkin lymphoma usually involves the mediastinum. However, pulmonary involvement is less common and can be observed in the lymph nodes, parenchyma, and tracheobronchial tree. ¹

It is worth mentioning that Hodgkin lymphoma with a tracheobronchial involvement remains extremely rare. ¹ Patients usually present with respiratory symptoms (such as dyspnea, wheezing and cough), fever, and weight loss. ² The diagnosis may be challenging because the symptoms are not specific. About (30%) of the patients have more than 6-months diagnosis delay. ³ We should consider a tracheobronchial tumor in the differential diagnosis when the patient presents to our department with asthma symptoms without any improvement after bronchodilators. In our case, the patient complained of a dry cough and chest wheezing mimicking an asthma attack. She received Beta2-mimetics without any improvement.

Atelectasis is the most frequent radiological finding, occurring in (2/3) of patients. Besides, the chest CT scan may reveal a solitary hilar mass or an obstructive emphysema. Mediastinal or hilar lymphadenopathy are often present. ⁴

Endoscopy may show ulceration, mucosal infiltrate, or a polypoid mass. ¹ Our patient had a polypoid mass rising from the trachea extended to the main bronchus.

Histopathology shows typically large Sternberg cells with positive staining for CD15 and CD30. ³ The diagnosis was made thanks to a biopsy of the supra-clavicular adenopathy in this case. Recent studies suggest that endobronchial ultrasound (EBUS) may be useful in the diagnosis and staging of Hodgkin lymphoma with endobronchial involvement to avoid mediastinoscopy. ⁵

It is worth mentioning that the PET scan is a reliable imaging tool for the diagnosis as well as for the staging of lymphoma especially in this case because mediastinal adenopathy may be due to infectious or inflammatory diseases. ^{6 , 7} In our case, this exam revealed an intense metabolic fixation FDG in many ganglionar areas as well as an endotracheobronchial fixation. It is also very interesting for the follow-up.

Treatment is commonly based on chemotherapy with or without radiotherapy. It depends strongly on the extent of the disease, the general state and the comorbidities. ⁸ Complete resection of the stenotic tracheal tumor may be performed in patients with critical airway obstruction thanks to interventional procedures such as rigid bronchoscopy with a stent placement, photodynamic laser therapy, laser therapy with a neodymium: yttrium-aluminum-garnet laser (Nd-YAG) and photodynamic laser therapy. ^{9 , 10}

Relapsed Hodgkin lymphoma is another challenging problem for clinicians especially when it affects the tracheobronchial tree as seen in our case. Prognostic Factors associated to the relapse of the disease have been recently identified including: a poor performance status (PS), an age greater than 50 years old, failure to achieve remission after an initial therapy, anemia and an advanced lymphoma with a clinical staging (III or IV). ¹¹

Conclusion

To conclude, we report a rare case clinical presentation of Hodgkin lymphoma with an endobronchial involvement. It should be considered in the differential diagnosis of asthma or in case of a tracheal tumor. Further studies are required in order to highlight the importance of interventional endoscopy procedures in the diagnosis as well as in the treatment of these cases and to find out the prognostic factors in order to improve the outcomes.

Consent

Written informed consent for publication of their clinical details and/or clinical images was obtained from the family of the patient.

Funding Statement

The author(s) declared that no grants were involved in supporting this work.