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Year : 2017  |  Volume : 60  |  Issue : 2  |  Page : 272-274
Hodgkin's lymphoma with unusual pulmonary presentations: Reporting two cases

1 Department of Pathology, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA, USA
2 Department of Pathology, University of California, 9500 Gilman Drive; Department of Pathology, Veteran Administration Medical Center, 3350 La Jolla Village Drive (113), La Jolla, San Diego, CA, USA
3 Department of Medicine, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA, USA

Click here for correspondence address and email

Date of Web Publication19-Jun-2017


Classical Hodgkin's lymphoma (CHL) presenting with exclusively pulmonary symptoms is very unusual. We report two cases of CHL with atypical clinical presentations mimicking pulmonary infections. The first case represents a stage IV CHL with secondary lung involvement, and the second case demonstrates a very rare case of CHL with isolated lung involvement, also known as primary pulmonary Hodgkin's lymphoma. The second patient was initially misdiagnosed and treated with six months of antibiotics before the correct diagnosis was made by a lung biopsy. Both patients received chemotherapy; one patient achieved complete remission and the other achieved near-complete remission.

Keywords: Classical Hodgkin's lymphoma, primary pulmonary Hodgkin's lymphoma, pulmonary involvement

How to cite this article:
Lowenthal BM, Xu X, Subash M, Jih LJ. Hodgkin's lymphoma with unusual pulmonary presentations: Reporting two cases. Indian J Pathol Microbiol 2017;60:272-4

How to cite this URL:
Lowenthal BM, Xu X, Subash M, Jih LJ. Hodgkin's lymphoma with unusual pulmonary presentations: Reporting two cases. Indian J Pathol Microbiol [serial online] 2017 [cited 2022 Aug 11];60:272-4. Available from: https://www.ijpmonline.org/text.asp?2017/60/2/272/208406

   Introduction Top

Classical Hodgkin's lymphoma (CHL) is a lymphoid neoplasm composed of multinucleated Reed–Sternberg (RS) cells and mononucleated Hodgkin's cells. It has a bimodal age distribution with the first peak at 15–35 years of age and the other peak much later in life. CHL commonly presents with localized cervical and mediastinal lymphadenopathy. Most patients present with stage I or II disease, and with the present treatment, most achieve long-term survival.[1] We present two patients with atypical pulmonary presentations of CHL.

   Case Report Top

Case 1

A 27-year-old previously healthy male presented with nonproductive cough, night sweats, and a 15-pound unintentional weight loss over 7 months. Extensive infectious workup was negative. Imaging studies revealed extensive bilateral upper lobe consolidations with bilateral hilar lymphadenopathy [Figure 1]a. Bronchoscopy demonstrated extrinsic compression and edema of the bronchi in the bilateral upper lobes and two left-sided endobronchial nodules [Figure 1]b. Endobronchial brushing and transbronchial biopsy were obtained.
Figure 1: Case 1 - radiographic and bronchoscopic findings. (a) Computed tomography of the thorax showing moderate to large bilateral lung consolidations with hilar lymphadenopathy. (b) Bronchoscopy demonstrating two left-sided endobronchial sessile nodules (arrows)

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Endobronchial brushing cytology revealed rare, large atypical mononucleated and binucleated cells with prominent nucleoli suspicious for Hodgkin's and RS cells [Figure 2]a. Concurrent lung biopsy showed dense inflammatory infiltrate with rare large atypical cells morphologically similar to those seen on the endobronchial brushing [Figure 2]b. Immunohistochemical studies demonstrated that these atypical cells were negative for CD45 [Figure 2]c, CD3, and anaplastic lymphoma kinase 1 (ALK-1). They were positive for CD30 [Figure 2]d, CD15 (subset) and weakly positive for Pax5 (Ventana Medical Systems, Tucson, AZ). Epstein–Barr virus in situ hybridization (EBV-ISH) (Epstein–Barr encoding region [EBER]) was negative. The findings were diagnostic of CHL.
Figure 2: Case 1 - cytological, histological, and immunohistochemical features of the endobronchial nodules. (a) Endobronchial brushing demonstrating rare diagnostic binucleated Reed-Sternberg cell (Papanicolaou, ×1000). (b) Biopsy of the endobronchial nodules demonstrating occasional large atypical cells (arrows), in a background of marked mixed inflammatory infiltrates comprised of neutrophils, histiocytes, lymphocytes, and abundant eosinophils (H and E, ×400). (c) The atypical cells were negative for CD45 (arrows, ×400). (d) The atypical cells were strongly positive for CD30

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A staging workup revealed a negative bone marrow biopsy. Positron emission tomography-computed tomography (PET-CT) demonstrated hypermetabolic bilateral perihilar consolidations with associated lung nodules and hypermetabolic bilateral cervical, left supraclavicular, and mediastinal lymph nodes. The radiographic findings were consistent with stage IV CHL. The patient had completed six cycles of chemotherapy with doxorubicin, vinblastine, dacarbazine, and etoposide (AVD-E) and achieved complete remission at 6 months after initial diagnosis.

Case 2

A 35-year-old healthy male presented with a 5-month history of dry cough, fevers, night sweats, and a 20-pound unintentional weight loss. He was previously treated with antibiotics at an outside hospital with no relief of symptoms. A chest CT highlighted dense consolidations of the left upper lobe and lingula with central cavitation and multiple small cavitary nodules in the left lower lobe. No significant mediastinal or hilar lymphadenopathy was noted. Acid-fast bacilli sputum smear was positive; however, confirmatory tests for mycobacterial infection were negative. All other infectious workup was negative. The patient was placed on anti-tuberculosis therapy but had no clinical improvement after 3 months of treatment. A bronchoscopy was performed which revealed no abnormality. He was placed on multiple antibiotic regimens for another 3 months and had no clinical or radiological improvement.

A second bronchoscopy with transbronchial biopsy was performed. The transbronchial biopsy showed scattered atypical cells with convoluted and smudgy nuclei in a background of prominent mixed inflammatory cells [Figure 3]b. By immunohistochemistry, these atypical cells were negative for CD45 [Figure 3]c, CD3, CD4, CD7, CD15, CD20, ALK-1, AE1/AE3. They were strongly positive for CD30 [Figure 3]d and weakly positive for Pax5. EBV-ISH (EBER) was negative. The findings were consistent with CHL.
Figure 3: Case 2 - radiographic findings, histological and immunohistochemical features of the lung biopsy. (a) Whole-body positron emission tomography-computed tomography demonstrating innumerable hypermetabolic pulmonary nodules with central cavitation and mildly hypermetabolic hilar lymph nodes. (b) Transbronchial lung biopsy demonstrating scattered atypical cells with irregular and smudgy nuclei (arrows), in a prominent mixed inflammatory background (H and E, ×400). (c) The atypical cells were negative for CD45 (arrows, ×400). (d) They were strongly positive for CD30 (×400)

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A staging bone marrow was negative for lymphoma involvement. PET-CT highlighted innumerable hypermetabolic cavitary pulmonary masses and mildly hypermetabolic hilar lymph nodes [Figure 3]a. The overall pattern of disease distribution was consistent with primary pulmonary Hodgkin's lymphoma (PPHL). The patient underwent four cycles of AVD-brentuximab, vedotin chemotherapy, and follow-up imaging at 8 months posttreatment revealed near-complete resolution of the pulmonary masses.

   Discussion Top

Pulmonary involvement by CHL is commonly seen during the disease. It occurs as a secondary involvement through lymphangitic extension from adjacent lymph nodes or through hematologic spread. Lung involvement by CHL typically presents as multiple nodules or masses on imaging studies.[2] Cavitation and “pneumonia-like” consolidation patterns are rare.[2],[3],[4] Both of our patients presented with symptoms and radiographic findings highly concerning for pulmonary infections. In the second case, patient was placed on prolonged antibiotic treatment despite negative microbiologic workup. The lack of considering CHL in the differential diagnosis resulted in a significant delay in obtaining tissue biopsy for a definitive diagnosis.

CHL with predominant lung involvement, also known as PPHL, is extremely rare with less than 100 reported cases.[5],[6],[7],[8],[9],[10] The disease is thought to arise from intraparenchymal lymphoid follicles or peribronchial lymph nodes. The largest case series reviewed by Radin included 61 cases of PPHL published between 1972 and 1986. The author observed that there was a slight female predilection with a bimodal distribution similar to nodal CHL. Common presenting symptoms were cough and dyspnea. The disease typically involves the upper lobes as single or multiple nodules, with nodular sclerosis PPHL as the most common histologic subtype.[9]

The gold standard for diagnosis of CHL requires the identification of RS cells and Hodgkin's cells on tissue biopsy. Diagnosis of CHL by cytology has always been challenging due to the scant quantity of diagnostic RS or Hodgkin's cells. In addition, these lesional cells may be overlooked in a dense inflammatory background or misinterpreted as reactive pneumocytes or other neoplastic entities. Therefore, in young patients presenting with atypical pulmonary symptoms and imaging findings, a cytologic sample containing a mixed inflammatory background, especially with abundant eosinophils, should prompt the pathologist to thoroughly search for RS or Hodgkin's cells.

   Conclusion Top

CHL is a relatively common lymphoma with high remission rate. Our cases demonstrate rare pulmonary presentation of CHL in young patients and the importance of considering it in the differential diagnosis to ensure timely diagnosis and treatment.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Piccaluga PP, Agostinelli C, Gazzola A, Tripodo C, Bacci F, Sabattini E, et al. Pathobiology of hodgkin lymphoma. Adv Hematol 2011;2011:920898.  Back to cited text no. 1
Diederich S, Link TM, Zühlsdorf H, Steinmeyer E, Wormanns D, Heindel W. Pulmonary manifestations of Hodgkin's disease: Radiographic and CT findings. Eur Radiol 2001;11:2295-305.  Back to cited text no. 2
Baccari-Ezzine S, Bouzaidi K, Chelbi E, Ali MB, Ghrairi H. Unusual radiologic and histologic manifestations of primary pulmonary lymphoma. Asian Cardiovasc Thorac Ann 2014;22:362-4.  Back to cited text no. 3
Bakan ND, Camsari G, Gur A, Ozkan G, Bayram M, Gorgulu F, et al. A 21-year-old male with productive cough, hemoptysis, chest pain, and weight loss. Respiration 2007;74:706-9.  Back to cited text no. 4
Kern WH, Crepeau AG, Jones JC. Primary Hodgkin's disease of the lung. Report of 4 cases and review of the literature. Cancer 1961;14:1151-65.  Back to cited text no. 5
Schild MH, Wong WW, Valdez R, Leis JF. Primary pulmonary classical Hodgkin lymphoma: A case report. J Surg Oncol 2014;110:341-4.  Back to cited text no. 6
Lluch-Garcia R, Briones-Gomez A, Castellano EM, Sanchez-Toril F, Lopez A, Brotons B. Primary pulmonary Hodgkin's lymphoma. Can Respir J 2010;17:e106-8.  Back to cited text no. 7
Rodriguez J, Tirabosco R, Pizzolitto S, Rocco M, Falconieri G. Hodgkin lymphoma presenting with exclusive or preponderant pulmonary involvement: A clinicopathologic study of 5 new cases. Ann Diagn Pathol 2006;10:83-8.  Back to cited text no. 8
Radin AI. Primary pulmonary Hodgkin's disease. Cancer 1990;65:550-63.  Back to cited text no. 9
Yousem SA, Weiss LM, Colby TV. Primary pulmonary Hodgkin's disease. A clinicopathologic study of 15 cases. Cancer 1986;57:1217-24.  Back to cited text no. 10

Correspondence Address:
Lily J Jih
3350 La Jolla Village Drive (113), San Diego, CA 92161
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_687_16

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