| Abstract|| |
A 60-year-old female presented with dyspnea, cough, and chest pain with a left hilar mass lesion. In our case, clinicoradiological correlation, bronchoscopy, and computed tomography-guided biopsy revealed the diagnosis of primary pulmonary non-Hodgkin's lymphoma (PPNHL) on histopathology and immunohistochemistry. We discuss the approach to hilar masses. PPNHL is a rare malignant lymphoma most common being mucosa-associated lymphoid tissue lymphoma. Various therapeutic options are available. The chemotherapy regimen consisting of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) is preferred.
Keywords: Computed tomography, flexible fiberoptic bronchoscopy, primary pulmonary non-Hodgkin's lymphoma
|How to cite this article:|
Utpat K, Desai UD, Amonkar G, Joshi JM. A perplexing primary novel hilar lesion: Remember the pneumonic PPNHL!. Indian J Pathol Microbiol 2018;61:85-9
|How to cite this URL:|
Utpat K, Desai UD, Amonkar G, Joshi JM. A perplexing primary novel hilar lesion: Remember the pneumonic PPNHL!. Indian J Pathol Microbiol [serial online] 2018 [cited 2020 Aug 9];61:85-9. Available from: http://www.ijpmonline.org/text.asp?2018/61/1/85/228188
| Introduction|| |
The differential diagnosis of hilar mass lesions is varied with a wide spectrum. A clinical, radiological, and further investigative approach narrows the differentials to reach the diagnosis. Primary pulmonary non-Hodgkin's lymphoma (PPNHL) is a rare malignancy presenting as a hilar mass.
| Clinical Protocol|| |
A 60-year-old female was referred with complaints of dry cough, exertional breathlessness (modified medical research council Grade 2 progressing to Grade 3), and left-sided dull aching chest pain for 1 month. She had diabetes mellitus and was on therapy for 3 years with oral hypoglycemic agents. There was no significant past and personal history. She had no addictions. She was a homemaker with no exposure to any organic/inorganic dust.
| Clinical Examination and Investigations|| |
The general examination was normal. There was no peripheral lymphadenopathy. Examination of chest revealed signs of volume loss of the left hemithorax in view of decreased movements, flattening, ipsilateral tracheal shift, shoulder droop, decreased spinoscapular distance, dull note on percussion, and decreased breath sounds. The clinical diagnosis was left lung collapse with an obstructed bronchus. The chest X-ray showed a left hilar mass lesion [Figure 1]. A contrast-enhanced computed tomography (CT) of the chest was performed to confirm the diagnosis. It demonstrated a well-defined heterogeneously enhancing mass lesion with irregular borders in the left upper and lingular lobe measuring 8 cm × 8.5 cm × 11 cm with few areas of calcification and breakdown within. The mass invaded the left main bronchus up to 2.2 cm from carina with resultant bronchus cutoff, the left atrial appendage, pericardium, and descending branch of the left pulmonary artery [Figure 2].
|Figure 1: The chest X-ray posteroanterior view showing a left hilar mass lesion|
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|Figure 2: Computed tomography of thorax (mediastinal and lung windows) showing left upper and lingular lobe mass|
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| Course in Hospital|| |
The patient was hospitalized for further evaluation. A flexible fiberoptic bronchoscopy (FOB) revealed complete obliteration of the left main stem bronchus 2 cm distal to the carina with irregular ragged mucosa [Figure 3]. An endobronchial biopsy was obtained from the diseased site. A CT-guided biopsy of the mass lesion was also performed. A 18 F-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET-CT) suggested the mass to be metabolically active with high-grade FDG uptake (SUVmax-18.04) with pericardial streaming. No additional uptake was noted. The CT-guided and bronchoscopy endobronchial biopsies on histopathological analysis showed fragments of bronchial mucosa with dense lymphoid cell infiltrate comprising admixed population of small lymphocytes and atypical large cells which were CD20 positive on immunohistochemistry (IHC) [Figure 4]a and [Figure 4]b. The patient was referred to the specialized oncology services for chemotherapy.
|Figure 3: Bronchoscopy image showing left main bronchus obliteration with irregular ragged mucosa|
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|Figure 4: (a) The computed tomography- and bronchoscopy-guided endobronchial biopsy histopathological image showing fragments of bronchial mucosa with dense lymphoid cell infiltrate comprising admixed population of small lymphocytes and atypical large cells under (H and E ×40). (b) The computed tomography- and bronchoscopy-guided endobronchial biopsy histopathological image showing CD20 positivity under ×10 on immunohistochemistry|
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| Unit's Final Diagnosis|| |
Our final diagnosis was left upper lobe and lingular mass lesion with endobronchial extension of mostly malignant etiology.
| Discussion on Clinical Protocol by the Professor, Pulmonary Medicine|| |
This elderly female presented with a short history of exertional dyspnea, dry cough, and dull aching chest pain. This symptomatology can be encountered with any infectious, inflammatory, or malignant condition of the thorax. However, the absence of fever made the presence of any infectious entity less likely. Further, on examination, she exhibited the clinical signs of collapse with an obstructed bronchus in the form of volume loss and reduced breath sounds over the left hemithorax that further narrowed down our differentials and made malignancy the most likely possibility. Her chest radiograph showed a left hilar lesion. A hilar mass lesion can arise from the lung or mediastinum. The differential diagnosis of hilar lung lesions is astronomical. It spans a heterogeneous histopathological and radiological spectrum. Various groups subsumed are (1) infectious – tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis, nocardiosis, lung abscess, round pneumonia, and hydatid cyst, (2) inflammatory (noninfectious) nodules – rheumatoid arthritis, Wegener's granulomatosis, sarcoidosis, and lipoid pneumonia, (3) benign lung tumors – bronchial cystadenomas, papillomas, lipoma, hemangiomas, neural tumors, fibroma, benign clear cell tumor, plasma cell granulomas, fibrous histiocytoma, xanthoma, and pulmonary endometrioma, (4) thoracic malignancies – bronchogenic carcinoma, lymphomas, lung metastasis, carcinoids, adenoid cystic carcinomas, leiomyoma, and teratoma, (5) congenital abnormalities – arteriovenous malformation, pulmonary sequestration, and bronchogenic cyst, and (6) miscellaneous causes – pulmonary infarct, rounded atelectasis, mucoid impaction, and progressive massive fibrosis. The differential diagnosis of mediastinal masses is as per the location of the lesion [Figure 5].
- Anterior mediastinum – thymus related (thymomas, thymolipomas, thymic carcinoma), teratomas, retrosternal thyroid enlargement (multinodular goiter, thyroid malignancies), lymphomas, and lymphadenopathy
- Middle mediastinum – lymphadenopathy, pericardial cyst, duplication cyst, aortic arch anomaly, fibrovascular polyp, and esophageal cyst
- Posterior mediastinum – neurogenic (neurogenic cyst, neurogenic tumors, schwannoma, meningocele), extramedullary hematopoiesis, and descending aorta anomaly.
The flow chart for evaluation of hilar lesions is summarized in [Figure 6]. The demographic data and clinical presentation first point toward the probable etiology. A chest radiograph posteroanterior (PA) view is a preliminary investigation that will confirm and localize the lesion. It can be labeled as a solitary pulmonary nodule (SPN) or mass lesion. An SPN is defined as a round or oval opacity smaller than 3 cm in diameter that is completely surrounded by pulmonary parenchyma; not associated with lymphadenopathy, atelectasis, or pneumonia. Nodules of >3 cm in size are most often malignant and termed as pulmonary masses. Hilar mass lesions are hilar opacities more than 3 cm in size. The radiologists often use the terminology “coin lesion” which is defined as a solitary lesion of 1–5 cm in size, homogenous, round or oval with well-defined margins surrounded by normal lung, with or without the presence of calcification., A lateral radiograph should be obtained in all cases to confirm the lobar localization and rule out superimposed chest wall lesions on the PA view. A previous chest radiograph will determine the volume doubling time (VDT) of the lesion. VDT is defined as the interval it takes for a nodule to double in volume. It is to be kept in mind that because a nodule is generally spherical, an increase in the diameter by just 28% or 1.2 cm actually represents a doubling of the volume of a nodule. Although it was said that a VDT of <20 days and more than 400 days ruled out malignancies in most cases as the former implied infectious/inflammatory causes and the later benign lesions, studies have shown exceptions to this rule in case of aggressive and indolent malignancies., Sputum cytology is important in the diagnosis, more so in early diagnosis of roentgenographically occult lung cancer. The utility of CT thorax is toward localizing the lesion, its extent, calcification, contrast enhancement, attenuation, air bronchogram, speculated irregular lobulated margins, presence of cavitation, associated satellite lesions, lymphadenopathy, and pleural effusions with diagnosis of associated comorbid conditions such as chronic obstructive pulmonary disease. CT-guided transthoracic fine needle biopsy and cytology are among the most important diagnostic procedures. Where either CT-guided or bronchoscopy-guided biopsy is not feasible, a PET-CT assessment followed by a lung resection surgery, i.e., wedge resection, lobectomy is considered in cases with high index of suspicion of malignancy. Otherwise in benign conditions, the patient can be kept under observation with follow-up CT at 3–6 months. PET-CT assessment was important in this particular case to call it a primary malignancy. Also for such lymphomas, it is essential to have at least one whole body investigation to rule out disseminated disease or to stage the disease FOB is of diagnostic and limited therapeutic importance. Endobronchial biopsy for histopathological evaluation, brush cytology, and bronchial washings cytology can be obtained. The tumor-bronchus relationship Type I and II usually predicts a good yield of bronchoscopy procedures. This classification by Tsuboi et al. is as follows: Type 1 – the bronchial lumen is patent till the tumor, Type 2 – the bronchus is contained in the tumor mass, Type 3 – the bronchus is compressed and narrowed by the tumor but the bronchial mucosa is intact, and Type 4 – the proximal bronchus is narrowed by peribronchial or submucosal spread of the tumor or enlarged lymph nodes such that the tumor cannot be reached [Figure 7]. Bronchoscopy-guided transbronchial needle aspiration from the subcarinal and hilar lymph nodes help in staging of malignancy. Newer technologies such as autofluorescence, narrow band imaging, electromagnetic navigation, optical coherence tomography, and confocal fluorescent laser microscopy can detect early lung cancer. Endoscopic ultrasound methods were developed in the last two decades, and as the technical problems interfering with ultrasound application in air-containing spaces were solved, endobronchial ultrasound (EBUS) became a valuable technique for targeted cytology. With EBUS, the delicate multilayer structure of the tracheobronchial wall can be analyzed. A transducer produces and receives the sound waves. Processor integrates the data and generates ultrasound images. The probe is provided with a balloon which if inflated with water improves the image quality by securing good contact with the airways. The probe is introduced through the working channel of a conventional bronchoscope, visualizes the lesion, and withdrawn. The view is 30° from the horizontal and the bronchoscopist compensates accordingly. A sheath can be left in situ to localize and stabilize the lesion during the subsequent introduction of forceps or brush for sampling. Therapeutic FOB is used for symptomatic relief of central airway obstruction or postobstructive complications in unresectable/inoperable lung cancer and for parenchyma-sparing surgery.
| Final Clinical Diagnosis|| |
A case of Left upper lobe and lingular mass lesion of malignant etiology to rule out lymphoma.
| Pathology Protocol by Associate Professor Pathology|| |
The CT-guided and bronchoscopy endobronchial biopsies on histopathological analysis showed fragments of bronchial mucosa with dense lymphoid cell infiltrate comprising admixed population of small lymphocytes and atypical large cells. On IHC, the atypical large cells stained positive for CD20. CD3 stain highlighted the admixed small lymphocytes. Stain for MIB-1 was equivocal. The diagnosis of diffuse large B-cell lymphoma was favored [Figure 4]a and [Figure 4]b.
| Final Diagnosis|| |
Left upper lobe and lingular mass lesion due to PPNHL (diffuse large B-cell type).
| Clinicopathologic Correlation|| |
Extranodal lymphomas commonly involve the gastrointestinal tract, skin, and central nervous system followed by the lungs. Primary pulmonary lymphomas (PPL) account for 3%–4% of all extranodal lymphomas. PPL are lymphomas limited to the lungs and the hilar lymph nodes. There is no evidence of extrapulmonary tumor at diagnosis and subsequently for at least 3 months. PPL are usually mucosa-associated lymphoid tissue (MALT) lymphomas, diffuse high-grade B-cell lymphomas, or lymphomatoid granulomatosis. Our case is of a diffuse high-grade diffuse NHL. Diffuse high-grade NHL constitutes around 11%–19% of all cases of PPL. They usually occur in the 6th decade and present as solitary mass as seen in our case too. These PPLs are usually associated with immunodeficiency state; however, our case did not have any such predisposing condition. Our case showed large atypical cells and sometimes these may be confused with carcinoma, melanoma, or sarcoma. Histopathological examination revealed bronchial mucosa with dense lymphoid cell infiltrate comprising of large atypical large cells. On IHC, the atypical large cells stained positive for CD20. IHC confirmed the diagnosis of diffuse high-grade B-cell lymphoma.
| Brief Comment on Primary Pulmonary Non-Hodgkin's Lymphoma|| |
The thoracic NHL could arise from the mediastinal lymph nodes or the lung lymphatics. Primary mediastinal B-cell NHL (PMBCL) arises in the mediastinum and PPNHL originates in the lung tissue. PMBCL is a rare neoplasm with unique clinicopathologic features and a molecular gene expression signature reminiscent of nodular sclerosis NHL. PPNHL is a very rare neoplasm represented most commonly by marginal zone B-cell lymphoma of MALT type. PPNHL is extremely rare and by definition the tumor is limited to the lung with no evidence of extrapulmonary disease. There may be hilar lymph node involvement. MALT lymphomas are the most common type of PPNHL. Diffuse large B-cell lymphoma, lymphomatoid granulomatosis, and high-grade lymphomas such as Burkitt's lymphoma and T-cell lymphomas are other rarer types of PPNHL. On IHC, MALT lymphomas are CD19+, CD20+, and negative for CD5, cyclin D1, CD10, and CD23. There are several treatment options for PPNHL such as tumor resection, radiation, and surgery followed by adjuvant treatment or chemotherapy alone, but the consensus has not been established., CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) regimen is the preferred chemotherapy regimen.,
| Conclusion|| |
PPNHL though extremely rare is a differential diagnosis of a hilar lung mass with a different line of management compared to the more common bronchogenic carcinoma.
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
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Jyotsna M Joshi
Department of Pulmonary Medicine, 2nd Floor, OPD Bldg, TNMC and BYL Nair Hospital, Al Nair Road, Mumbai Central, Mumbai - 400 008, Maharashtra
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]