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  Table of Contents  
Year : 2015  |  Volume : 52  |  Issue : 5  |  Page : 37-40

Synchronous primary pulmonary lymphoma presenting with pulmonary adenocarcinoma: A case report and literature review

Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China

Date of Web Publication3-Nov-2015

Correspondence Address:
Z Gao
Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.168955

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 » Abstract 

The incidence of synchronous lung tumors is rare, as reported in various clinical series, ranging from 0.2% to 8%. Most reported cases of synchronous tumors were shown to have the same histologic types of lung cancer. Among possible combinations, squamous cell carcinoma was by far the most common. Primary pulmonary lymphoma (PPL) is very rare in clinics accounting for only 0.5–1% of primary lung tumors. There is no report about synchronous primary pulmonary adenocarcinoma presenting with lung lymphoma. It can be easily misdiagnosed or missed. Although the treatment of PPL and synchronous pulmonary tumors has controversial, surgery with/without postoperative adjuvant radio-chemotherapy are used for most patients in present. We describe a case of synchronous primary lung tumors presenting with lymphoma and adenocarcinoma, in which expression of the cell surface antigens were evaluated immunohistochemically. By taking into consideration of the reported experiences, the author discusses the clinical features, prognostic criteria and therapeutic management of synchronous lung cancer and PPL.

Keywords: Diagnosis, primary pulmonary lymphoma, synchronous primary pulmonary tumors, treatment

How to cite this article:
Zheng J X, Li X Z, Xiang R L, Gao Z. Synchronous primary pulmonary lymphoma presenting with pulmonary adenocarcinoma: A case report and literature review. Indian J Cancer 2015;52, Suppl S1:37-40

How to cite this URL:
Zheng J X, Li X Z, Xiang R L, Gao Z. Synchronous primary pulmonary lymphoma presenting with pulmonary adenocarcinoma: A case report and literature review. Indian J Cancer [serial online] 2015 [cited 2022 Dec 5];52, Suppl S1:37-40. Available from:

 » Introduction Top

Synchronous lung cancers are rare. Most of the reported cases of synchronous lung cancers were shown to have the same histologic types. Among possible combinations, squamous cell cancers are the most common.[1] Primary pulmonary lymphoma (PPL) is a rare extranodal lymphomas which are B-cell types and are considered to originated from the mucosa-associated lymphoid tissue (MALT). There has been no report about synchronous primary lymphoma and adenocarcinoma of the lung.

 » Case Report Top

An 81-year-old male was referred to our hospital for an evaluation of abnormal chest X-ray findings. No abnormalities were noted upon physical examination. Chest computed tomography (CT) [Figure 1] was performed, which revealed a soft tissue lesion in the middle lobe of right lung, and consolidation with air bronchogram in right lower lobe. On positron emission tomography (PET) imaging, the two lesions standardized uptake value were high, typical for malignant lesions. Tumor markers of CYF211, carcinoembryonic antigen and neuron specific enolase were in normal range. Examination by CT of the chest, ultrasonography of the abdomen, magnetic resonance imaging (MRI) of the brain, as well as bone scan and PET revealed no extrapulmonary metastases or primary tumors. A video-assisted thoracoscopic surgery was performed. Intraoperative exploration revealed a lesion in right middle lobe measuring 5 cm × 4 cm, soft, invading partial upper lobe, and a lesion in right lower lobe measuring 3 cm × 3 cm, soft, without invading the pleural. Intraoperative pathology showed middle-low differentiated adenocarcinoma in the middle lobe and MALT lymphoma in the right lower lobe. Thus, we decided to perform right middle lobectomy, partial lobectomy of the right lower lobe, and systematic lymph node dissections. The postoperative course was uneventful. On immunohistochemistry (IHC) [Figure 2], the neoplastic cells from the lesion of right middle lobe stained positive for cytokeratin (CK), vimentin, CK7, thyroid transcription factor (TTF-1), napsin A, negative for CK5/6, P63, CD56, Syn, and CgA, which is compatible with moderately-poorly differentiated adenocarcinoma. The proliferation index (Ki-67) appeared to be approximately 50% in moderately-poorly differentiated adenocarcinoma cells. The pathological stage of the pulmonary adenocarcinoma is Ib. The IHC of neoplastic cells [Figure 2] from the lesion of lower lobe of right lung revealed CD3 (focally+), CD20 (diffusely+), CK and TTF-1 (alveolar epithelium+), CD21 and CD23 (showing follicular dendritic cell net), CD138 (focally+), CD38 (focally+), kappa (+), lamba (−MALT cells. The pathological stage of the pulmonary MALT is IE. Through a comprehensive gene expression analysis and drug susceptibility examination of the two tumors, we knew both were susceptible to pemetrexed disodium. In consideration of the age and the general condition of the patient, we used pemetrexed disodium (500 mg/m 2) alone as the chemotherapy for six cycles (21 days for each cycle). The chest CT detected no newly lymphadenectasis at postoperative 6 months. Bone metastasis was detected in ilium and lumbar vertebra 8 months after surgery. Moreover, the patient died of respiratory and circulatory failure associated with the progression of the tumors at postoperative 9 months.
Figure 1: (a and b) Computed tomography scans of the chest showing a soft tissue lesion in right middle lobe and a consolidation with air bronchogram in the right lower lobe

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Figure 2: (a) Microscopy findings on biopsy from adenocarcinoma of right middle lobe, immunohistochemistry staining showing sarcomatoid structure can be seen in part of the tumor tissue, bronchioles alveolar structure can be seen in peripheral lung tissue, (×200) (b and c) microscopy findings on biopsy from adenocarcinoma of right lower lobe, immunohistochemistry staining is diffusely positive for (b) CD20 and (c) CD21

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 » Discussion Top

The estimated incidence of synchronous lung cancers is very low, as reported in various clinical series, ranging from 0.2% to 8%.[2] Approximately, 60% of synchronous second primary lung cancers are squamous cell cancers; in approximately 60% of the cases, the tumors are of the same histologic type.[1] There has been no report about synchronous primary lymphoma and adenocarcinoma of the lung.

In the aspects of diagnosis, the distinction between multiple synchronous primary lung cancers and intrapulmonary metastases is often difficult. As a result, the rate of misdiagnosis is high. The first clinicopathological criteria were initially proposed by Martini and Melamed in 1975 and then were further extended by the American College of Chest Physicians (ACCP) guidelines (2007 edition). The guideline reveals that if the tumors are the same histology the tumors should be anatomically separated or in different lobes without N2, 3 involvement, and systemic metastases; if different histology type, they should be different type or different molecular genetic characteristics or arising separately from foci of carcinoma in situ.[3] Even so the disease can be easily misdiagnosed. It can reduce the rate of misdiagnosis to correlate molecular findings and genetic features with clinicopathological criteria. The need for fresh frozen tissue makes the technique more applicable to synchronous tumors.[4] The demonstration of clonality of multiple lung tumors has been generally based on the occurrence of somatic mutations in oncogenes or tumor suppressor genes, X-chromosome inactivation analysis, or loss of heterozygosity (LOH) analysis.[5],[6] P53 alteration either alone or together with p53, 3p deletion, is useful to distinguish the clonal origin of multiple lung tumors, especially in cases with similar histopathological features.[7] Shimizu et al., reported that synchronous and metachronous lung tumors with identical histology were successfully distinguished from intrapulmonary metastases using LOH assay.[6] The combination of LOH analysis with P53 mutation profiling increases specificity and sensitivity in the diagnosis of synchronous independent primary lung cancers.[6] Array comparative genomic hybridization, which is based on the identification of copy number changes across the genome, has been recently shown to distinguish independent from common origin tumors with very high confidence rates.[8]

The diagnosis of synchronous double lung cancer is definite according to the radiology appearance and postoperative pathology. As reported, about a third of synchronous lung cancer are discovered perioperatively or postoperatively in the resected tissue in patients undergoing surgery. Concerning the clinical stage of synchronous lung cancer, the two tumors should be staged separately and managed as distinct tumors.[9] According to the most recent ACCP guidelines on the treatment of nonsmall cell lung cancer (NSCLC), in patient with two synchronous primary NSCLCs being considered for curative surgical resection, invasive mediastinal staging, and extrathoracic imaging (head CT/MRI plus either whole-body PET or abdominal CT plus bone scan) are recommended to clarify the stage of the two tumors.[10]

Surgical treatment is accepted the first treatment way for synchronous double lung cancers, provided that the clinical stage of the two tumors and the patient's cardiopulmonary reserves permit it. Synchronous lung cancers are more frequently located in the same lung. They are mainly treated with anatomical resections, especially single, double lobectomy, or pneumonectomy.[11],[12] Anatomical resection of the first tumor and subsequent sublobar resection might be a safe and beneficial alternative approach for synchronous bilateral lesions.[11],[12] ACCP recommended that each tumor should be resected completely provided that the patient has an adequate pulmonary reserve, and there is no N2 nodal involvement.[3] In this case, considering that the tumor was in the right middle and lower lobe and the poor cardiopulmonary reserve of the patient, we performed right middle lobectomy and wedge resection of the right lower lobe. In our opinion, the initial surgery should be performed on the side with the largest lesion, especially when there are doubts on tumor resectablity, and contralateral recession should then follow. Stereotactic body radiotherapy (SBRT), has emerged as a novel radiation modality with significant applications for early-stage lung cancer. As reported, that the efficacy, feasibility, safety of SBRT has been established when treating multiple primary lung cancer and it can be a new standard of care for patients with medically inoperable multiple Stage I NSCLCs.[13] Varlotto et al., concluded that there was no significant difference in overall survival, overall control rates of recurrence between SBRT and operation.[14]

The prognostic factors include lymphoma involvement,[12] older age,[15] incomplete tumor resection.[11] Okada reported that lymph node involvement was considered the best predictor of survival in patients with multiple lung cancers.[12] Different histological type of the two tumors [16] and sublobar resection [15] did not seem to have any effect on 5-year survival. The 5-year survival for all patients ranges from 0% to 70%, consistent with the difficulty of reliably classifying these tumors.[3] The 5-year survival for the patients who were received operation is about 25%.[10] Eight months after the operation, the patients was found with lumbar and ilium metastases, 9 months after the operation, the patient was dead for respiratory failure. Thus, the progression of the tumors is rapid.

PPL is a rare entity, accounting for 0.4% of all malignant lymphoma and 0.5–1% of all pulmonary malignancies.[17] The incidence of PPL peaks in the sixth and seventh decades of life, and the ratio of male to female patients is close to 1:1.[18] PPL can be divided into Hodgkin lymphoma (HL) and non-HL (NHL), NHL consists the majority of PPL with MALT, which is accounting for 70–80% of primary pulmonary NHL.[17],[19],[20] PPL is usually an NHL, and according to the World Health Organization's classification system, it can be divided into two types: MALT and non-MALT. The former mainly includes low-grade marginal zone B-cell lymphoma, the latter includes diffuse large B-cell lymphoma and anaplastic large cell lymphoma.[21],[22] Primary pulmonary MALT is thought to be acquired as a result of chronic antigenic stimulation such as smoking, autoimmune disease, or infection.[17]

The disease frequently has an indolent course, and the clinical manifestation is nonspecific. Concerning the radiographic appearance, air space consolidation with air bronchograms is the most frequent imaging in up to 65–70% of the cases and pleural effusion in 25% of the cases,[23] multiple lesions can be present in up to 25% of the patients.[24] Wislez et al., concluded that the specific radiographic manifestation of PPL is a consolidated mass with air bronchograms.[25] As a result of its rarity, it is difficult to distinguish PPL from tuberculosis, lung cancer, and intrapulmonary metastasis. So far, pathological examination is still an important way to differentiate PPL from other lung disease.

A commonly used set of criteria for PPL proposed by L'Hoste and associates is lymphoma with (1) involvement of the lung, lobar, or primary bronchus, with or without mediastinal involvement, and (2) no evidence of extrathoracic lymphoma at the time of diagnosis or for 3 months thereafter.[24] Concerning the stage of PPL, the Ann Arbor staging system has been widely used for lymphomas of all types and is summarized in [Table 1].[26] In this case, CT shows consolidated mass with air bronchograms in the right lower lobe, and there is no evidence of extrathoracic lymphadenectasis 6 months after the operation. Thus, the diagnosis of PPL is definitely and the postoperative pathological stage is IE.
Table 1: Ann Arbor pulmonary lymphoma staging system

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The treatment options include watch and wait approach, surgery in localized tumors, chemotherapy if the lesions are diffuse or involve both lungs and radiotherapy. However in the absence of comparative series, the efficacy of this treatment cannot be analyzed. Surgery is generally accepted as the first treatment. Through surgery, we can get a definite diagnosis and the basis for the next step treatment. Cordier et al.[27] considered 60–70% of patients suitable for surgery. Kawashima et al.[28] concluded surgery was the first selection for tumors confined to the chest, provided that cardiopulmonary reserve of the patient permit it. Hu et al.[19] reported that patients who had received surgery tended to have a better 5-year overall survival. The MALTomas are slow growing tumors with an indolent course; tend to be localized and, therefore, amenable to surgery (73% complete resection was achieved).[20] Patient with the huge lesion and remained tumor after operation should receive postoperative adjuvant chemotherapy. In China cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) was generally chosen as the chemotherapy for PPL. Furthermore, the Italian Society of Hematology produced clinical practice-guidelines for the management of these rare tumors. In patients with MALT or non-MALT primary lung NHL, the panel of expert recommended first-line therapy, combination regimens with anthracycline-based chmotherapy or monotherapy in association or not with rituximab. In addition, for patients with MALT primary lung NHL surgical resection can be the treatment of choice in localized tumor if complete resection can be achieved. Radiotherapy is to be reserved for patients with a unique, small lesion and observation only can be an alternative in an asymptomatic patient with the localized disease.[29] In this case, in consideration of the patient's cardiopulmonary reserves, we performed a wedge resection of the right lower lobe, following right middle lobection. Patients with locally resectable tumor up to Stage II 2EW should receive surgery and lymph node involvement, and bilateral disease does not appear to be a contraindication to surgery.

Most of the studies confirm the relatively favorable prognosis of patients with PPL irrespective of the treatment modalities. One large series of 70 patients reported a 94% survival at 5-year for low-grade PPL, and a median survival of 3 years for high-grade disease.[18],[20],[21] The 5-year survival rate of MALT is 68% and the 10 years survival rate is 53%.[17] The prognostic factors influencing survival are The histologic type, T-cell lymphoma,[30] the presence of pleural effusion as well bilateral disease [31] and the need for adjuvant therapy.[20] Although there are reports about the large-cell transformation of MALT lymphomas to high-grade lymphoma, the rate is very low. In this case, the short postoperative survival mainly resulted from the rapid progression of the moderately-low differentiated carcinoma.

 » References Top

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  [Figure 1], [Figure 2]

  [Table 1]

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