Pulmonary T-cell lymphoma masquerading as eosinophilic pneumonitis.

Primary pulmonary T-cell lymphoma is an unusual subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). This is a general term used to describe a diverse group of T-cell-type lymphomas that would otherwise not be classified as a PTCL. Among non-Hodgkin's lymphomas, PTCL accounts for 12% of cases. PTCL-NOS accounts for approximately 25% of all PTCL cases. Primary pulmonary T-cell lymphoma is associated with unfavorable outcomes and has a poor prognosis. Being a rare disease, epidemiological data regarding primary pulmonary T-cell lymphoma continues to be sparse at this time. We present a case of PTCL, which was misdiagnosed as eosinophilic pneumonitis (EP) based on samples obtained from transbronchial cryobiopsy. To our knowledge, this is the first reported case of PTCL masquerading as EP.

INTRODUCTION

Primary pulmonary T-cell lymphoma is a rare subtype of non-Hodgkin's lymphoma that has an aggressive course with a high associated mortality.[12] Diagnosis is generally necessitated by transbronchial biopsies or a computed tomography (CT)-guided needle biopsy obtained for pathology interpretation. Awareness of the unique presentation of this disease will aid in better diagnosis in the proper clinical setting. This article presents a case of pulmonary T-cell lymphoma masquerading as eosinophilic pneumonitis (EP) and reviews recent literature for diagnostic and management considerations for peripheral T-cell lymphoma (PTCL).

CASE REPORT

A 47-year-old woman presented with a several weeks' history of fever, nonproductive cough, shortness of breath, and audible wheezing. Initial vital signs showed temperature 98.8°F, pulse 82 beats/minute, blood pressure 119/86 mmHg, respiration rate 20 breaths/minute, and oxygen saturation of 92% on room air. Physical examination revealed bilateral rhonchi at the lung bases. The rest of her physical examination was unremarkable. Of note, the patient had been recently discharged after a 10-day admission for community-acquired pneumonia, which was diagnosed based on clinical presentation and findings of bilateral pulmonary infiltrates on chest X-ray. She was treated with intravenous (IV) antibiotics, oral steroids, and nebulized bronchodilators. Now, her shortness of breath had progressed to the point that it was present at rest. The patient had recently quit smoking and moved into a used mobile home that had mold.

Initial blood tests showed an elevated white blood cell count of 17, with notable peripheral eosinophilia of 34%. Chest X-ray and CT chest scan showed bilateral pulmonary infiltrates [Figure 1a and b]. Blood, urine, and sputum cultures were all negative for growth. Fungal workup was performed with negative Candida antigen, urine/blood histoplasma antigen, serum beta-D-glucan, and serum Aspergillus galactomannan. Immunoglobulin E (IgE) level was normal, and serum Aspergillus antigen testing was negative. The eosinophilia was further investigated, and the ova and parasite screen was negative. In addition, collagen vascular disease workup was negative. CT of the chest, abdomen, and pelvis confirmed the presence of bilateral lung infiltrates and demonstrated no evidence of neoplasm in the abdomen and pelvis [Figure 1c]. Treatment for suspected pneumonia with broad-spectrum IV antibiotics was initiated.

Figure 1

(a) Chest X-ray revealing bilateral patch pulmonary opacities with consolidation. (b) Computed tomography chest from initial hospitalization showing bilateral airspace opacities. (c) Subsequent hospitalization computed tomography chest showing diffuse bilateral airspace opacities which had worsened compared to prior imaging.(d) Computed tomography abdomen showing new liver lesions

With no resolution of symptoms, the patient eventually underwent bronchoscopy. On bronchoscopy, copious mucoid secretions were noted in the airways. Bronchoalveolar lavage and three transbronchial cryobiopsy specimens from the right upper lobe were obtained. Cryobiopsy of the lung showed chronic and acute inflammatory infiltrates with significantly increased eosinophils and focal fibrosis with eosinophilic inflammation on biopsy [Figure 2]. Based on the constellation of peripheral eosinophilia, bilateral infiltrates, and eosinophilic inflammation on cryobiopsy of the lung, a diagnosis of EP was made. The patient was discharged home with oral steroids and counseled on the possibility of the black mold in her home having caused these symptoms. Unfortunately, 2 weeks later, the patient was admitted for profound shortness of breath and hypoxia. CT chest showed worsening of lung infiltrates, and a CT abdomen showed new liver lesions [Figure 1c and d]. She continued to deteriorate during her hospitalization and required intubation. Despite optimization of ventilator support, antibiotics, and steroids, the patient eventually died before a liver biopsy could be performed. On autopsy, histopathological analysis revealed diffuse eosinophils in all organs. Subsequent immunohistochemistry staining showed positive staining for CD5 and CD30 (T-cell markers) and negative stains for CD20 (B-cell marker) [Figure 3]. These findings were demonstrative of the diagnosis of aggressive diffuse PTCL.

Figure 2

Transbronchial cryopbiopsy of the lung shows pulmonary parenchyma with focal anthracotic pigment deposition, type II hyperplasia, and extensive chronic and acute inflammatory infiltrate with significantly increased eosinophils

Figure 3

On autopsy, histopathological analysis revealed diffuse eosinophils in all organs. Subsequent immunohistochemistry staining showed positive staining for CD5 and CD30 (T-cell markers), and negative stains for CD20 (B-cell marker) (a and b). Hematoxylin and eosin staining negative for CD20. (c) Positive staining for CD5 (d) Positive staining for CD30

DISCUSSION

Primary pulmonary T-cell lymphoma is rare and only accounts for a small percentage of PTCLs.[3] Primary PTCL often presents as a cutaneous pathology, but it may also present in extracutaneous forms. PTCLs are generally divided into several subtypes: anaplastic large cell, angioimmunoblastic, extranodal NK/T-cell, adult T-cell, hepatosplenic, mycosis fungoides/Sezary syndrome, subcutaneous panniculitis-like T-cell lymphoma, and PTCL not otherwise specified (NOS).[45] This case would be described as a PTCL-NOS, which is a term used to describe types of PTCL that do not fall under the other categories. They typically show cytological and phenotypic heterogeneity. However, they generally consist of small and large atypical cells in addition to eosinophils and macrophages likely recruited by local inflammatory cytokines.[6] PTCL surface antigen expression is largely variable, with the majority expressing CD2, CD3, CD4, CD5, and CD7.[47] Most patients with PTCL usually present with generalized lymphadenopathy, eosinophilia, fever, and weight loss. These tumors often have a more sinister prognosis compared to its B-cell counterpart. This patient presented with fever, eosinophilia, and weight loss, but she did not have lymphadenopathy. The patient's presentation was largely consistent with EP. She had fever, dyspnea, and peripheral infiltrates, and peripheral eosinophilia with normal IgE level. She initially somewhat responded to steroids.

Diagnosis of diffuse parenchymal lung diseases including EP is best achieved by surgical lung biopsy. There is emerging literature, which suggests that transbronchial cryobiopsy may be a useful alternative to surgical lung biopsy in diagnosing diffuse parenchymal lung diseases.[8] Results from different studies suggest the diagnostic yield for cryobiopsy is variable, and surgical lung biopsy continues to be the gold standard for diagnosis of parenchymal lung disease. There is no literature that discusses PTCL or pneumonitis diagnosis with transbronchial cryobiopsy. There are several factors that cause cryobiopsy results to be variable – these include operator technique, freeze time, and probe size.

Treatment of primary pulmonary T-cell lymphoma is similar to the treatment of patients with aggressive non-Hodgkin's lymphoma.[9] First-line therapy per National Comprehensive Cancer Network (NCCN) guidelines consist of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based or etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)-based chemotherapy.[910] Unfortunately, median progression-free survival is approximately 1 year, with only 30% of patients being alive and free of disease 5 years after the treatment.[11] NCCN guidelines recommend consolidative radiotherapy in all PTCL patients with Stage I or II disease who achieved remission after standard CHOP- or EPOCH-based therapy.[10]

CONCLUSION

Based on our literature review, we found this to be the first case of primary pulmonary T-cell lymphoma masquerading as EP – with inability to arrive at correct diagnosis with transbronchial cryobiopsy. This type of PTCL is extremely rare, and the resultant diagnostic challenges often mean a grim prognosis for the patient. However, despite this poor prognosis, a high index of suspicion may lead to early diagnosis and can aid in early treatment. While emerging diagnostic techniques such as transbronchial cryobiopsies hold promise in interstitial lung diseases, their role in rare conditions remains unknown, and therefore, clinical correlation should always be exercised while interpreting histopathology findings.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.