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Forty years literature review of primary lung lymphoma.
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PMID:  21371331     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There are several unresolved issues through out the literature regarding the entity of primary lung lymphoma. Extensive literature review of this uncommon pathology is carried out. By taking into consideration the reported experience, the author discuss the classification, clinical features, histological differential diagnosis, prognostic criteria, therapeutic management and outcome of primary lung parenchyma lymphocytic infiltrates.
Authors:
Haralabos Parissis
Publication Detail:
Type:  Journal Article; Review     Date:  2011-03-03
Journal Detail:
Title:  Journal of cardiothoracic surgery     Volume:  6     ISSN:  1749-8090     ISO Abbreviation:  J Cardiothorac Surg     Publication Date:  2011  
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Created Date:  2011-03-15     Completed Date:  2011-07-19     Revised Date:  2013-06-30    
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Nlm Unique ID:  101265113     Medline TA:  J Cardiothorac Surg     Country:  England    
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Languages:  eng     Pagination:  23     Citation Subset:  IM    
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Cardiothoracic Dept, Royal Victoria Hospital, Belfast, Northern Ireland. hparissis@yahoo.co.uk
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MeSH Terms
Descriptor/Qualifier:
Diagnosis, Differential
Disease Progression
Humans
Lung Neoplasms / diagnosis*
Lymphoma / diagnosis*
Prognosis
Time Factors
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Journal ID (nlm-ta): J Cardiothorac Surg
ISSN: 1749-8090
Publisher: BioMed Central
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Copyright ©2011 Parissis; licensee BioMed Central Ltd.
open-access:
Received Day: 4 Month: 11 Year: 2010
Accepted Day: 3 Month: 3 Year: 2011
collection publication date: Year: 2011
Electronic publication date: Day: 3 Month: 3 Year: 2011
Volume: 6First Page: 23 Last Page: 23
ID: 3056730
Publisher Id: 1749-8090-6-23
PubMed Id: 21371331
DOI: 10.1186/1749-8090-6-23

Forty years literature review of primary lung lymphoma
Haralabos Parissis1 Email: hparissis@yahoo.co.uk
1Cardiothoracic Dept, Royal Victoria Hospital, Belfast, Northern Ireland

Introduction

Primary Lung Lymphoma (PLL) is a rare entity (0.4% of all lymphomas[1] & 3.6% of non- Hodgkins lymphomas[2]) of heterogenous group of patients with some common characteristics: 1) difficult to be diagnosed due to an indolent course (with a tendency to relapse) with a non specific clinical and radiological presentation 2) low diagnostic yield and 3) sometimes difficult to differentiate from pseudo-lymphomas and 4)overall good outcome especially in disease amenable to surgical resection.

The main diagnostic criterion for PLL is the absence of extra-pulmonary involvement. That means unilateral or bilateral involvement of the lung with or without hilar or mediastinal lumph node involvement and with or without chest wall involvement [3]. Therefore, in patients with biopsy-proven lymphoma of the lung, PLL is diagnosed if extra-pulmonary involvement is ruled out.

In this article we aim to review the literature in order to delineate from the surgeons prospective, the overall experience of the rare entity of PLL and also to bring up to date the variables leading to a favorable outcome following surgery.


Materials and methods

Pertinent medical literature in the English language was identified through a Medline computerized literature search and a manual search of selected articles using as Key-words: Primary pulmonary Lymphoma, Lung Lymphoma, Pseudolymphoma of the lung, Non-Hodgkin lymphoma of the lung or extranodal lymphoma. The search terms were combined using the Boolean operator term "or" to find all abstracts pertaining to the chosen search terms. These individual terms were then combined using the Boolean operator term "and" to find articles that contained information of all search terms (as per Greenhaligh et al)[4]. The reference lists of articles found through these searches were also reviewed for relevant articles. Links provided on the web sites of published articles were searched for relevant articles. The primary search yielded 81 relevant articles. Of those 14 were excluded as they pertained to pseudolymphoma.

The Ann Arbor pulmonary lymphoma staging system was used for classification

Stage

IE: Lung only, could be bilateral

II 1E: Lung and hilar lymph nodes

II 2E: Lung and mediastinal lymph nodes

II 2EW: Lung & chest wall or diaphragm

III: lung and lymph nodes below the diaphragm

IV: diffuse

Characteristics of the various reports

We reviewed the reported literature from 1966 to 2007. We divide the reports into 2 groups. The first group (Table 1[5-62]) contains case reports with fewer patients compare to the second group (Table 2[63-71]).


Results
Group A

58 reports were identified and reviewed. There were 309 cases of PLL. The largest series in this group [58] included 31 patients.

Non Hodgkin Lymphomas (nHL) consist the majority of PLL with mucosa-associated lymphoid tissue (MALTomas) being 70-80%. Hodgkin lymphoma was reported in a small number of cases 1.5-2.4%.

The course of the disease is long and indolent spanning from 1.5 to 108 months [31].

Radiological appearance have shown that non specific patchy opacities or mass-like consolidation was the case in the majority of the patients (up to 68%) and multiple nodules in more than 50% of the cases. [31,57,58].

Nodal involvement (stage II1E, II2E) was reported in 35%-45% of the cases [6,18,58].

Bronchoscopy obtained a diagnostic yield in 30%-40% [20,48] of the cases and invasive surgical procedure revealed the diagnosis in up to 70% of the cases[20].

There was no uniform protocol throughout the literature regarding the indications for surgery. Despite nodal involvement (stage II 1E and 2E) surgery was advocated in few studies [33] and some authors concluded that several treatment methods can be used to achieve good outcomes [23].

Group B

The second group consisted of 506 reported cases of PLL.

In the majority of the studies the male to female ratio is variable (from 1/1 [68] to 1/2 [70]). Average age of disease presentation is 53±12 years [65,68-70]. 83% of the patients have been reported to be above 40 years of age [65].

Symptoms are present in 2/3 of the patients (62.5% to 78% of patients) [69,70]. The mean duration of symptoms was 5 months [65]. Mild symptoms with no resolving consolidation should be managed with a high index of suspicion.

Again, nHL consist the majority of PLL with MALTomas being 60-78% [69-71].

The radiographic appearance shows nodules or mass lesions in 60-72%,[69,70]. Single lesions are present in 55% of the cases [65]. Multiple nodules are present in 40% of the patients [65,67]. Bilateral disease varies in different reports: 21%. [68], 27%[65], 39% [70], 44% [69].

Nodal involvement (stage II1E, II2E) was reported in 28 to 39% of the cases [65,69] and Pleural effusions 15-22%[69,70].

There was again, no uniform protocol throughout the literature regarding the indications for surgery. Nevertheless, surgery was advocated in 60-70% of the patients. The MALToma patients tend to have complete resections. Broadly speaking, following surgery, patients had more favorable outcome [71].

Diagnosis

The role of monoclonal protein in the electrophoresis of serum protein: ie. Serum IgG >5000 mgr/dl has been stated in some reports [19,21,51]. Stained for Kappa & Lambda chains, using the immunoperoxidase technique on paraffin sections has been reported. Serum protein electrophoresis abnormalities could be present in up to 33% of the cases [65]. Serum or immunofluorescence monoclonal gammopathy should exclude pseudoL. Furthermore the presence of a serum monoclonal gammopathy is associated with worse prognosis [66].

The significant role of Broncho Alveolar Lavage (BAL) with a cell count of plasma cells of 40% and lymphocytes of 17% with prominence of CD19 positive lymphocytes has been reported by Umino et al [51]. IgG/albumin ratio 13 times higher and IL-6/albumin ratio 29 times higher in lavage fluid than in serum. Furthermore TBLB and immunohistochemical stains mainly CD20 could be helpful. DNA extraction from the surgical specimen and PCR reveals rearrangement band of the genes to the heavy chain immunoglobulin (Fr3a & VLJH primers) [51]. The diagnostic value of Cell surface markers analysis using fresh tissue was also stated in some reports [35,65].

Staging workup should include bone marrow biopsy and CT of the abdomen to exclude extrathoracic disease. Lymphangiograms and bone scans could be part of the preoperative staging [65].

The role of PET scan is equivocal due to the low avidity and the multifocal nature of the disease. The low yield of bronchoscopy and Transcutaneous needle CT guided biopsy has been stated in few reports[13,20]. There is however, a high role for VATS or open surgical lung biopsy with a diagnostic yield more than 90%.

Histology

PLL arises from centrocyte-like cells normally present in bronchus associated lymphoid tissue. Monomorphic cell population and invasion of bronchial cartilage, pleura or lymph nodes are suggestive of malignancy. Some cases of PLL appeared as complications of a pre existing dysimmune disease (Pigeon breeder disease), Gougerot-Sjogren, Lymphomatoid granulomatosis (LYG) and Liebows lymphomatoid granulomatosis)[12,19,32].

The gross classification of Low Grade malignant Lymphoma higher grade MALTomas (large cell type) and others (ie. Follicular, Diffuse large B-cell, anaplastic large cell)

has been used through out the literature. A detail attempt to estimate the biological potential of lymphomas by their histologic type and correlate this with outcome was attempted with the use of various systems of histologic classification of non Hodgkins lymphomas.

Although from the surgeons prospective the classification seems complicated, one could grossly divide the tumors into small round lymphocytes (50-60%), with varying degrees of plasmacytic change, ("plasmacytoid" well differentiated) and large lymphocytic tumors.

More specifically the Kiel classification [32] essentially differentiates Lymphoplasmacytic (LP) from Centroblastic lymphoma (CB). The LP type is the most common (55-65%) [65]. The tumor is composed of uniform small round lympocytes; they often grow as solid masses; infiltration of bronchial and vascular wall is often however necrosis does not present. The incidence of recurrence is less than 35% through out the literature [65].

Contrary CB type makes up 40% of the cases. It consists of a centrocytic diffuse or follicular population including the rare immunoblastic type. In general those tumors are aggressive, present as pulmonary infiltrates therefore are not amenable to surgical resection and have a higher tendency to recur.

The term MALTomas was described by Bienenstock et al [72]. They are the most common amongst nHL (76% according to Cordier et al). The MALTomas are characterized by: extranodal, small lymphocytic b-cell tumor, cellular heterogeneity, infiltration of the bronchial mucosa by centrocyte cells and presence of reactive lymphoid follicles. The etiology of this mucosal transformation is probably acquired in response to long-term exposure to various antigenic stimuli; Synchronus MALTomaS involving the lung, stomach & ocular adnexa have been reported in the literature [68,70].

Pulmonary lymphomas of nH type could be divided into 4 groups [48]according to the properties and behavior of the tumor: B-cells small or medium size (those tumors are frequently associated with consolidations and air bronchograms), B-cell large lymphoid cell (frequently radiologic presentation is consistent with a mass) and T-cell tumors (bad prognosis). Furthermore the REAL classification sums up the histological variations of all types of lymphomas [73] however, from the surgical prospective it is detailed and probably not widely applicable.

Differentiating between Lymphoma (especially Lymphoplasmacytic (LP) type) and pseudolymphoma

Mixture of mature lymphocytes and plasma cells with reactive follicles are suggestive of pseudolymphoma.

Pulmonary pseudolymphoma is a rare lesion; Up till 1980, only 30 cases were reported in the literature. True lymphoma was developed in four cases [34].

The diagnosis of pseudolymphoma is based on: 1) pulmonary nodules composed of cytologically benign lymphoid cells 2) presence of infiltrates with plasma cells, histiocytes and monocytes 3) presence of germinal centers. In addition, the presence of pleural effusion does not preclude the diagnosis of pseudolymphoma.

Immunological studies aim to define whether the lymphoid proliferation is monoclonal or polyclonal. It is suggested that PPL arises from centrocyte-like cells normally present in bronchus -associated lymphoid tissue. In addition to malignant population reactive follicles and polytypic plasma cells are frequently present so one should be aware that cases previously diagnosed as pseudo-lymphoma or lymphoid interstitial pneumonia need to be reconsidered. Moreover when recurrent tumors are present then pseudo L is rare; however pseudolymphomas do not necessary follow a benign course [18]

Surgical Treatment strategies

Resection rate varies from series to series [18,37,68,69]. There are no guidelines as to when surgery is indicated. While reviewing the literature one gets the impression that surgery is advocated on an institutional basis.

Surgery for solitary lesions and adjuvant therapies for more extensive disease has been the general consensus. Overall 60-70% of the patients with PLL are surgical candidates [68]; however, incomplete resection is reported to be the case in more than 50% of the cases [69]. Surgical candidate could potentially be any patient with locally resectable tumor up to stage II 2EW. Lymph node involvement does not appear to be a contraindication to surgery. Likewise bilateral disease could also be tackled surgically. However the surgical ablation of such lesions must be economical [37] because of frequent recurrence, sometimes bilateral. Hu et al [71] concluded 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; tent to be localized and therefore amenable to surgery (73% complete resection was achieved [69]).

Combined modality therapy appears to be superior in patients with bulky disease, residual disease following operation and an unfavorable non-MALT type of histology.

Recurrence rates

Pulmonary recurrences are either within the ipsilateral lung or in both lungs. Extrapulmonary recurrent disease occurs mainly in lymph nodes, however skin, bone marrow or visceral organs could be affected [63,65].

The overall local recurrence rate is 50% [69]. More specifically the incidence of recurrence for the LP group is 33% with an average time of 69 months versus 50% for the CB group [65].

The median time to disease recurrence or death has been reported to be 6-7 years [70,68]. Late recurrences up to 14 years have also been reported [23].

There are not enough data in the literature regarding Surgery for recurrences; nevertheless the general consensus dictates that recurrences should be treated with aggressive chemotherapy regimes.

Survival data

This is a heterogenous group of patients. Nevertheless the overall reported median time to death was 7 years or the overall reported mean survival was 71.3 months. More specifically for low grade lymphomas the median survival was 117 months and for disseminated lymphoma 33 months according to Kennedy et al [66].

The overall survival at 3 years was 86% and at 5 years 57% [68,65]. For the MALTomas the five year survival was 68% and the ten year 53% [69].

The prognostic factors influencing survival are: the histologic type, T cell lymphoma [67] the presence of pleural effusion [63] as well as bilateral disease and the need for adjuvant therapy [70]. In contrary according to Ferraro et al [69] complete Vs incomplete resection, the stage of the disease, the presence of mediastinal lumph node involvement or bilateral disease did not significantly influence survival.


Discussion

Extensive literature review of the medical literature the last 40 years was carried out. We have excluded cases of primary pulmonary AIDS related lymphoma and lymphoma following immuno-suppression and transplantation (200 fold higher than the general population).

The incidence of PLL has two peaks: the first on in the fifth decade of life and the second late six and seventh decade. The diagnostic criteria for PLL include bilateral pulmonary lesions as PPL. The reason for that is the fact that several of those patients when treated never showed evidence of extapulmonary involvement. Also the definition includes absence of extrapulmonary disease for 3 months following the initial diagnosis. This is because invariably extrathoracic and extranodular lymphoma may present (ie. Pulmonary and stomach Lymphoma)

High index of suspicious facilitates the diagnosis of this rare, indolent disease. One third of patients have no symptoms, furthermore out of the symptomatic cohort the duration of symptoms prior to the diagnosis is at least 5 months. Serum protein electrophoresis abnormalities are present in 33% of the patients [65].

The frequency of imagine features of PLL is difficult to assess in the literature because of varying radiological terminology & heterogeneity of several series including all lymphomas of the lung. The radiography is non informative (solitary nodule, multiple ill defined nodules, consolidated mass with air bronchograms, ground glass opacity or reticular lesions in one or both lung fields, pleura effusions, atelectasis and cavities) and non specific. Multiple lesions can be present in up to 25% of the patients [65], air space consolidation with air bronchograms is the most frequent imaging in up to 65%-70% of the cases and pleural effusions in 25% of the cases [31].

The histological classification having kept the principles of low grade (87% of the patients, as per Cordier et al[68]) and high grade disease, has evolved into more complex classifications taking into account the cell morphology and histological characteristics. Although, that does not necessarily correlate with prognosis the gross differentiation into MALTs and non MALTs somehow reflects prognosis[71].

The Staging systems considers bilateral pulmonary lesion as stage I disease and stage II as disease confined to the thoracic cavity;

Only surgical biopsy and resection obtains high yield (64% of the patients as per Cordier et al[68] & 90% of the patients as per Ferraro et al[69].

The prognostic factors affecting survival are not well defined; the stage of the disease, extend of resection (complete Vs incomplete) and the presence of mediastinal lymphadenopathy does is not associated with worse prognosis [69]. In contrary, the report by Hu et al [71] suggested that hilar or mediastinal node involvement negatively influences survival. Higher stage disease was associated with statistically not significantly worse outcome according to Graham et al [70]. The authors reported that bilateral disease was the most significant factor predicting disease recurrence and death.

The evaluations of the role of surgery as well as the indications for surgery are scarce in the literature; positive surgical margins do not alter survival therefore the role of surgery may be applicable in the majority of the cases following by chemotherapy.

The long term outcome of PLL is favorable; 56% of the patients recovered from the disease [70] with an overall 5 year survival across the border of >60% and a recurrence rate of less than 50%.

During the analysis of the presented series we observed a low consistency in publishing specific variables (ie. Incidence of recurrence, etc) and this precluded us from carrying out detailed statistics; therefore our paper carries the biases not only from the studies examined but also from its observational character. Nevertheless, we believe that our report has attempted to give an insight in this rare and not well addressed pathology.


Competing interests

The authors declare that they have no competing interests.


References
Rosenberg SA,Diamond HD,Jaslowitz B,Craver LF,Lymphosarcoma: A review of 1269 casesMedicineYear: 196140318410.1097/00005792-196102000-0000213743408
Freeman C,Berg JW,Cutler SJ,Occurrence and prognosis of extranodal lymphomasCancerYear: 19722925226010.1002/1097-0142(197201)29:1<252::AID-CNCR2820290138>3.0.CO;2-#5007387
Saltzstein SL,Pulmonary malignant lymphomas and pseudolymphomas: Classification, therapy and prognosisCancerYear: 19631692895510.1002/1097-0142(196307)16:7<928::AID-CNCR2820160709>3.0.CO;2-H14043765
Greenhaligh,et al. How to read a paper: the MEDLINE databaseBr Med JYear: 1997315180183
Gao J,Huang X,Wang R,Cai B,Lu W,Lin Y,Primary pulmonary lymphoma: analysis of cases and review of the literatureZhonghua Jie He He Hu Xi Za ZhiYear: 20022584847
Zhang LB,Sun YE,Yu CH,Liu Y,Clinical diagnosis and surgical treatment of primary pulmonary lymphomaZhonghua Wai Ke Za ZhiYear: 200644297916620666
Tian XL,Feng RE,Shi JH,Duan MH,Wang JL,Liu HR,Cai BQ,Gao JM,Xu WB,Zhu YJ,Primary pulmonary lymphoma: analysis of 18 cases
Varona JF,Guerra JM,Grande C,Villena V,Gonzalez-Lois C,Martinez MA,Primary pulmonary lymphoma: diagnosis and follow up of 6 cases and review of an uncommon entity
Peterson H,Snider HL,Yam LT,Bowlds CF,Arnn EH,Li CY,Primary pulmonary lymphoma. A clinical and immunohistochemical study of six casesCancerYear: 19855648051310.1002/1097-0142(19850815)56:4<805::AID-CNCR2820560418>3.0.CO;2-Q4016672
Muller C,Grivaux M,Schwattz F,Blanchon F,Primary pulmonary lymphoma. Current data. Apropos of 9 casesRev Pneumol ClinYear: 1990464166712100028
Mu XD,Wang GF,Diao XL,Que CL,A case of marginal zone B-cell lymphoma of the pulmonary mucosa- associated lymphoid tissue typeBeijing Da Xue Xue BaoYear: 20073943465017657256
Natali F,Merlet P,Le Vagueresse R,Allard P,Jourdain de Muizon H,Kermarec J,Primary pulmonary lymphomaRev Pneumol ClinYear: 1984406355626397824
Deng LP,Hu HJ,Zhang SZ,Dong DJ,Tan HQ,Radiological features of primary pulmonary non-Hodgkin lymphoma:report of three casesZhonghua Jie He He Hu Xi Za ZhiYear: 2003264223612901830
Nakachi S,Nagasaki A,Owan I,Uchihara T,Fujita J,Ohshima K,Miyagi T,Taira T,Taira N,Takasu N,Primary pulmonary Hodgkin lymphoma-two case reports and a review of the literatureGan To Kagaku RyohoYear: 2007341322798218079630
Martinez Rivera C,Bonnin Vilaplana M,Simon Adiego C,Palacin Forgue A,Puig Zuza J,Sampablo Lauro I,Primary pulmonary lymphoma presenting as a pulmonary mass with cavitationArch BronconeumolYear: 200440294614746733
Colby TV,Carrington CB,Pulmonary lymphomas simulating lymphomatoid granulomatosisAm J Surg PatholYear: 198261193210.1097/00000478-198201000-000027081533
Toh HC,Ang PT,Primary pulmonary lymphoma-clinical review from a single institution in SingaporeLeuk LymphomaYear: 1997271-2153639373207
Marchevsky A,Padilla M,Kaneko M,Kleinerman J,Localazed lymphoid nodules of the lung. A reappraisal of the lymphoma versus pseudolymphoma dilemmaCancerYear: 198351112070710.1002/1097-0142(19830601)51:11<2070::AID-CNCR2820511120>3.0.CO;2-R6839298
Morisako T,kobayashi H,Kanou S,Uwabe Y,Nagata N,Aoki T,Ozeki Y,Aida S,Tamai S,Clinicopathological study of six cases of primary pulmonary lymphoma diagnosed by gene rearrangement analysisNihon Kokyuki Gakkai ZasshiYear: 1998363236409656669
Kim JH,Lee SH,Park J,Kim HY,Lee SI,Park JO,Kim K,Kim WS,Jung CW,Park YS,Im YH,Kang WK,Lee MH,Park K,Han JH,Ko YH,Primary pulmonary non- Hodgkin lymphomaJpn J Clin OncolYear: 2004349510410.1093/jjco/hyh09515466823
Addis BJ,Hyjek E,Isaacson PG,Primary pulmonary lymphoma: a re-appraisal of its histogenesis and its relationship to pseudolymphoma and lymphoid interstitial pneumoniaHistopathologyYear: 1988131011710.1111/j.1365-2559.1988.tb02000.x3209184
Arinc S,Yilmaz A,Primary pulmonary lymphomaTuberk ToraksYear: 200654219720216924580
Xu HY,Jin T,Li RY,Ni YM,Zhou JY,Wen XH,Diagnosis and treatment of pulmonary mucosa-associated lymphoid tissue lymphomaChin Med JYear: 200712086485117517178
Pagani M,Antico A,Bellarosa S,Cavazzini G,Aitini E,Primary pulmonary high grade non-Hodgkin lymphoma in an elderly patient. A case reportTumoriYear: 2007936622418338502
Cao MS,Cai HR,Yin HL,Zhang DP,Xiao YL,Cao M,Dai LJ,Hou J,Primary natural killer/T cell lymphoma of the lung: two cases report and clinical analysisZhonghua Jie He He Hu Xi Za ZhiYear: 2008312120418683784
Baas AA,van Herwaarden CL,Primary non- Hodgkin lymphoma of the lungEur J Respir DisYear: 1986683218233699123
Ziade N,Khayat G,Sader-Ghorra C,Abadjian G,Primary pulmonary lymphoma. A case report and review of the literatureJ Med LibanYear: 200553150416398213
Habermann TM,Ryu JH,Inwards DJ,Kurtin PJ,Primary pulmonary lymphomaSemin OncolYear: 19992633071510375087
Uematsu M,Okada M,Ishii N,Watanabe N,Yasufuku M,Surgical treatment of primary pulmonary malignant lymphoma: a report of successful caseKyobu GekaYear: 1997504325309095596
Tillawi IS,Primary pulmonary Hodgkins lymphoma. A report of 2 cases and review of the literatureSaudi Med JYear: 2007286943817530115
Chu HQ,Ren SX,Yi XH,The clinical diagnosis and analysis of pulmonary mucosa associated lymphoid tissue lymphomaZhonghua Jie He He hu Xi Za ZhiYear: 2007303167917572992
Le Tourneau A,Audouin J,Garbe L,Capron F,Servais B,Monges G,Payan H,Diebold J,Primary pulmonary malignant lymphoma, clinical and pathological findings, immunocytochemical and ultrastructural studies in 15 casesHematol OncolYear: 198311496010.1002/hon.29000101076376312
Loh KC,Chan KW,Sng I,Primary pulmonary lymphoma:report of three cases and a brief review of the literatureAnn Acad Med SingaporeYear: 199423340057944259
Cordier JF,Bernaudin JF,Mary P,Guillaud C,Loire R,Brune J,Touraine R,Primary pulmonary pseudolymphomas and lymphomas.4 casesRev Mal RespirYear: 198412105116379786
Watanabe J,Yamaguchi K,Sugiyama Y,Yotsumoto H,Takaku F,Primary pulmonary lymphoma demonstration of monoclonality by lymphocyte surface marker studyJpn J MedYear: 1987263377803320430
Toishi M,Miyazawa M,Takahashi K,Hyogotani A,Haba Y,Kato K,Muramatsu A,Nishiyama M,Ozawa K,Nanbu A,Miyata K,Mucosa-associated lymphoid tissue lymphoma; report of two casesKyobu GekaYear: 200457175914733103
Jayet A,Wertheim U,Crausaz PH,Saegesser F,Pulmonary granuloma, pseudolymphoma and lymphomaHelv Chir ActaYear: 1980471-237407440206
Kuroishi S,Nakano Y,Ono T,Shirai m,Hayakawa H,Murakami M,Suda T,Chida K,Nakamura H,Kobashi Y,A case of primary pulmonary MALT lymphoma as a nodular shadow on CT scan, and relapsed with diffuse micronodular shadows after surgical resection at 7 years agoNihon Kokyuki Gakkai ZasshiYear: 20034112922714727557
Sakula A,Primary malignant lymphoma of lungPostgrad Med JYear: 19795563946910.1136/pgmj.55.639.46432173
Hashizume T,Honda A,Eto T,Akiyama J,Yamakawa H,Ikehara K,Ito M,Fujii M,Suzuki M,Arai K,Primary pulmonary lymphoma diagnosed from monoclonality of lymphocytes in a transbronchial biopsy specimenNihon Kyobu Shikkan Gakkai ZasshiYear: 19973519599071164
Gouldesbrough DR,McGoogan E,Primary pulmonary lymphoma: a case diagnosed by bronchial cytology and immunocytochemistryHistopathologyYear: 1988134465710.1111/j.1365-2559.1988.tb02064.x3265408
Bosanko CM,Korobkin M,Fantone JC,Rubin SB,Lynch JP,Lobar primary pulmonary lymphoma: CT findingsJ Comput Assist TomogrYear: 19911546798210.1097/00004728-199107000-000282061489
Chee YC,Yap CH,Poh SC,Pulmonary lymphoma or pseudolymphoma: a diagnostic dilemmaAnn Acad Med SingaporeYear: 198615111373707029
Bolton- Maggs PH,Colman A,Dixon GR,Myskow MW,Williams JG,Donnelly RJ,Hind CR,Mucosa associated lymphoma of the lungThoraxYear: 1993486670210.1136/thx.48.6.6708346501
Xu TR,Pulmonary lymphoma of mucosa-associated lymphoid tissue. A clinical, pathological, immunochemical and ultrastructural study of 2 casesZhonghua Jie He He Hu Xi Za ZhiYear: 1987105269703450414
Konig G,Huhn D,Albrecht J,Diagnosis of pulmonary manifestations of malignant lymphoma by bronchopulmonary lavagePrax Klin PneumolYear: 198640518353725733
Ehrenstein F,Primary pulmonary lymphoma. Review of the literature and two case reportsJ Thorac Cardiovasc SurgYear: 19665213195943112
Tamura A,Komatsu H,Yanai N,Homma J,Nagase A,Nemoto E,Hirai T,Hashizume T,Kawata K,Ishikawa S,Primary Pulmonary Lymphoma: relationship between clinical features and pathological finings in 24 cases. The Japan National Chest Hospital Study Group for Lung CancerJpn J Clin OncolYear: 1995254140527666590
Sakuraba M,Onuki T,Mae M,Yoshida T,Nitta S,Three cases of primary pulmonary malignant lymphomaNihon Kokyuki Gakkai ZasshiYear: 2000389714911109812
Abe Y,Hayashi A,Yasufuku K,Oiwa T,Kurosu K,Mikata A,Nihon Kokyuki Gakkai ZasshiYear: 199836440379691659
Umino T,Ohdama S,Sawada M,Tachibana S,Takano S,Miyake S,Aoki N,Yamamoto N,Matsubara O,Masuda S,A case of surgically resected primary pulmonary lymphoma with IgG-paraproteinemia: gene analysis was effective for establishing its diagnosisNihon Kokyuki Gakkai ZasshiYear: 199331810128
Zinzani PL,Tani M,Gabriele A,Poletti V,Stefoni V,Alinari L,Musuraca G,Bonifazi F,Pileri S,Tura S,Baccarani M,Extranodal marginal zone B-cell lymphoma of MALT type of the lung: Single center experience with 12 patientsLeuk LymphomaYear: 2003445821410.1080/104281903100006797212802920
Herbert A,Wright DH,Isaacson PG,Smith JL,Primary malignant lymphoma of the lung:histopathologic and immunologic evaluation of nine casesHum PatholYear: 19841554152210.1016/S0046-8177(84)80074-X6373559
Davis WB,Gadek JE,Detection of pulmonary lymphoma by bronchoalveolar lavageChestYear: 19879157879010.1378/chest.91.5.7873568787
Pisani RJ,Witzig TE,Li CY,Morris MA,Thibodeau SN,Confirmation of lumphomatous pulmonary involvement by immunophenotypic and gene rearrangement analysis of bronchoalveolar lavage fluidMayo Clin ProcYear: 199065565162190047
Sprague RI,deBlois GG,Small lymphocytic pulmonary lymphoma. Diagnosis by transthoracic fine needle aspirationChestYear: 19899649293010.1378/chest.96.4.9292676398
Julsrud PR,Brown LR,Li CY,Rosenow EC,Crowe JK,Pulmonary processes of mature-appearing lymphocytes: pseudolymphoma, well-differentiated lymphocytic lymphoma and lymphocytic interstitial pneumonitisRadiologyYear: 1978127228996580457
Lewis ER,Caskey CI,Fishman EK,Lymphoma of the lung:CT findings in 31 patientsAJR Am J RoentgenolYear: 1991156471142003430
Bellotti M,Elsner B,Esteva H,Mackinlay TA,Mazzei JA,Fiberoptic bronchoscopy in the diagnosis of pulmonary lymphomasRespirationYear: 1987523201410.1159/0001953253326083
Kilgore TL,Chasen MH,Endobronchial non-Hodgkins lymphomaChestYear: 1983841586110.1378/chest.84.1.586345101
Rose RM,Grigas D,Strattemeir E,Harris NL,Linggood RM,Endobronchial involvement with non-Hodgkins lymphoma. A clinical -radiological analysisCancerYear: 19865791750510.1002/1097-0142(19860501)57:9<1750::AID-CNCR2820570907>3.0.CO;2-J3955520
Oka M,Kawano K,Kanda T,Hara K,Bronchoalveolar lavage in primary pulmonary lymphoma with monoclonal gammopathyAm Rev Respir DisYear: 1988137495793355005
Koss MN,Hochholzer L,Nichols PW,Wehunt WD,Lazarus AA,Primary non-Hodgkins lymphoma and pseuolymphoma of lung: a study of 161 patientsHum PatholYear: 1983141210243810.1016/S0046-8177(83)80258-56642492
Turner RR,Colby TV,Doggett RS,Well-differentiated lymphocytic lymphoma. A study of 47 patients with primary manifestation in the lungCancerYear: 1984541020889610.1002/1097-0142(19841115)54:10<2088::AID-CNCR2820541008>3.0.CO;2-Y6386139
L Hoste R Jr,Filippa D,Lieberman P,Bretsky S,Primary Pulmonary Lymphomas. A clinicopathologic analysis of 36 casesCancerYear: 1984541397140610.1002/1097-0142(19841001)54:7<1397::AID-CNCR2820540728>3.0.CO;2-46467161
Kennedy JL,Nathwani BN,Burke JS,Hill LR,Rappaport H,Pulmonary lymphomas and other pulmonary lymphoid lesions. A clinicopathologic and immunologic study of 64 patientsCancerYear: 19855635395210.1002/1097-0142(19850801)56:3<539::AID-CNCR2820560322>3.0.CO;2-D3839161
Li G,Hansmann ML,Zwingers T,Lennert K,Primary lymphomas of the lung: morphological, immunohistochemical and clinical featuresHistopathologyYear: 19901665193110.1111/j.1365-2559.1990.tb01157.x2198222
Cordier JF,Chailleux E,Lauque D,Reynauld-Gaubert M,Dietemann-Molard A,Dalphin JC,Blanc-Jouvan F,Loire R,Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patientsChestYear: 199310320120810.1378/chest.103.1.2018417879
Ferraro P,Trastek V,Adlakha H,Deschamps C,Allen M,Pairolero P,Primary non Hodgkins lymphoma of the lungAnn Thorac SurgYear: 20006999399710.1016/S0003-4975(99)01535-010800781
Graham BB,Mathisen DJ,Mark EJ,Takvorian RW,Primary pulmonary lymphomaAnn Thorac SurgYear: 200580412485310.1016/j.athoracsur.2005.04.01416181848
Hu YH,Hsiao LT,Yang CF,Chiou TJ,Liu JH,Gau JP,Yen CC,Chou TY,Hsu WH,Chen PM,Tzeng CH,Prognostic factors of Chinese patients with primary pulmonary non-Hodgkins lymphoma: the single-institude experience in TaiwanAnn HematolYear: 2009 in press . 19139892
Bienenstock J,Johnston N,Perey D,Bronchial lymphoid tissueLab InvestYear: 197328686984123478
Harris NL,Jaffe ES,Stein H,et al. A revised European- American classification of lymphoid neoplasms: a proposal from the InternationalLymphoma Study GroupBloodYear: 1994841361928068936

Tables
[TableWrap ID: T1] Table 1 

Published Studies with small number of patients nHL: Non Hodgkin Lymphoma MALToma: mucosa-associated lymphoid tissue


Author Year Journal Number nHL MALT Comments/Outcome
Gao J[5] 2002 Zhonghua Jie He He Hu Xi Za Zhi 6 Misdiagnosis is common. Persistent cough is the most common symptom

Zhang L[6] 2006 Zhonghua Wai Ke Za Zhi 10 8 3 cases IE, 2 cases II 1E, 2 cases II 2E and 1 case of II 2EW. All patients had Pneumonectomy & ChemoTx. Survival > 17 months. Advanced (stage II 2E) B-cell low grade and Hodgkin disease lead to poor prognosis

Tian XL[7] 2008 Zhonghua Jie He He Hu Xi Za Zhi 18 7 9 CT features: nodules 14/18, Pleural effusion 5/18. Treatment with Surgery & CTx/RTx. Survival > 11 months: 13 pts, with one death and 4 patients lost to follow up

Varona JF[8] 2005 Tumori 6 6 Mono-CTx treatment with alkylating agents. The authors suggest that the outcome is favorable whatever the treatment modalities

Peterson H[9] 1985 Cancer 6 5 Authors suggest that the treatment is surgical resection and that Rtx and CTx are used when residual disease is present after surgery. Median time to death:48,6 months

Muller C[10] 1990 Rev Pneumol Clin 9 Treatment is surgical in localized forms; there is no firmly established treatment in extensive forms

Mu XD[11] 2007 Beijing Da Xue Xue Bao 1 1 MALT with features: consolidation of right middle lobe and left lower lobe, left pleural effusion with monocytes, monoclonal protein in the electrophoresis of serum, CD20 positive

Natali F[12] 1984 Rev Pneumol Clin 2 2 Discussion about PLL related diseases with a varying degree of malignancy: interstitial lymphocytic pneumonitis ILP, pseudolymphoma PL, lymphomatoid granulomatosis LYG

Deng L[13] 2003 Zhonghua Jie He He Hu Xi Za Zhi 3 3 Radiological features of 3 cases and the role of percutaneous biopsy

Nakachi S[14] 2007 Gan To Kagaku Ryoho 2 2 cases of PPHodgkinL

Martinez RC[15] 2004 1 1 PPL presenting as a pulmonary mass with cavitation

Colby TV[16] 1982 20 20?

Toh HC[17] 1997 Leuk Lymphoma 11 11 Mean age 50. Lower lobe involvement was the commonest. Small lymphocytic lymphoma was the most common. Good symptom control and radiologic response was achieved with chemotherapy

Marchevsky A[18] 1983 Cancer 5 Criteria for pseudolymphoma Vs PLL. 167 Cases in the literature were analyzed

Morisako T[19] 1998 Nihon Kokyuki Gakkai Zasshi 6 6 Southern blot analysis of lung biopsy: rearrangement of a heavy chain gene

Kim JH[20] 2004 Jpn J Clin Oncol 24 9 15 50% of the patients were asymptomatic at presentation. Bronchoscopy: 30% yield, 67% needed surgical procedure for diagnosis. Overall survival at 3 years: 86%

Addis BJ[21] 1988 Histopathology 15 The diagnosis was based in 13 cases: on Light chain restriction

Arinc S[22] 2006 Tuberk Toraks Review paper on the current approach in PLL

Xu HY[23] 2007 Chin Med J 12 12 Diagnosis and treatment of MALTomas. 2 pts also had gastric MALTS. Operation was performed on 6 patients. 4 pts treated with Chemo alone. Mean survival 71.3 months. One patient experience recurrence 152 months following operation. Several treatment methods can be used to achieve good outcomes

Pagani M[24] 2007 Tumori 1 1 Single case of right hilar LL.

Cao MS[25] 2008 Zhonghua Jie He He Hu Xi Za Zhi 2 cases of NK/T cell L. Also Literature review of 3 cases Aggressive tumors. Contrary to nHL most patients presents with symptoms.
Pleural effusions 4/5. Ebstein-Barr was positive in 3/5. Those tumors are CD56(+), CD3(+) but CD20(-). Most pts died within 6/12.

Baas AA[26] 1986 Eur J Respir Dis 1 1 Single case of a 49 y old man with multiple ill defined densities in both lungs treated successfully with Chemotherapy

Ziade N[27] 2005 J Med Liban 1 1 Single case of PLL in an elderly patient

Habermann TM[28] 1999 Semin Oncol Review article with an emphasis to observations in the clinical management and treatment of PLL

Uematsu M[29] 1997 Kyobu Geka 1 1 PLL of Rt middle lobe treated with lobectomy

Tillawi IS[30] 2007 Saudi Med J 2 2 cases of P Hodgkin lymphoma in young patients. CD30 and CD15 positive in RS cells were detected.

Chu HQ[31] 2007 Zhonghua Jie He He Hu Xi Za Zhi 13 13 MALT is more common in middle age males. Variable radiographic features; bilateral disease in more than 50% of the cases

Le Tourneau A[32] 1983 Hamatol Oncol 15 15 Reference to Kiel- Lennert histo pathological classification. Association of PLL of B type and dysimmune disease

Loh KC[33] 1994 Ann Acad Med Singapore 3 3 Interestingly, despite nodal involvement all patients had surgical resections and adjuvant ChTx. All 3 alive at 92, 51 and 12 months

Cordier JF[34] 1984 Rev Mal Respir 4 The article raises the possible hypothesis that pseudolymphoma may be the initial step in a large spectrum ranging from benign to malignant primary lymphoproliferative lung disorders

Watanabe J[35] 1987 Jpn J Med 1 1 The diagnostic value of surface marker analysis in primary B cell lung lymphoma is emphasized

Toishi M[36] 2004 Kyobu Geka 2 2 Report of 2 cases of MALToma treated with Surgery and post op RadioTherapy

Jayet A[37] 1980 Helv Chir Acta 10 This report emphasizes the fact that surgical treatment of PLL has to be "economical" due to the fact that frequent recurrences (sometimes bilateral) could be encountered

Kuroishi S[38] 2003 Nihon Kokyuki Gakkai Zasshi 1 1 A case of a lingular lobe PLL that relapsed with diffuse micronodular pattern 7 years following surgical resection

Sakula A[39] 1979 Postgrad Med J 1 1 A single case report

Hashizume T[40] 1997 Nihon Kyobu Shikkan Gakkai Zasshi 1 1 A single case report of PLL presented with bilateral infiltrative shadows

Gouldesbrough DR[41] 1988 Histopathology 1 A single case of PLL diagnosed by bronchial cytology and immunocytochemistry

Bosanko CM[42] 1991 J Comput Assist Tomogr 1 1 A single case report presented as an asymptomatic chronic lobar consolidation

Chee YC[43] 1986 Ann Acad Med Singapore 1 Report of a Pseudolymphoma case with a biclonal gammopathy

Bolton- Maggs PH[44] 1993 Thorax 2 2 Report of 2 cases of MALTomas, giving emphasis on the varied clinical and radiological features

Xu TR[45] 1987 Zhonghua Jie He He Hu Xi Za Zhi 2 2 Report of 2 cases of MALTomas, giving emphasis on the varied clinical and pathological features

Konig G[46] 1986 Prax Klin Pneumol 1 The role of BAL in diagnosis of PLL

Ehrenstein F[47] 1966 J. Thorac Cardiovasc Surg 2 2 2 cases of PLL

Tamura A[48] 1995 Jpn J Clin Oncol 24 24 PLL: relationship between clinical features and pathologic findings Pulmonary LL were divided into 4 groups Bcell tumors composed of small to medium size lymphoid cells have the best prognosis

Sakuraba M[49] 2000 Nihon Kokyuki Gakkai Zasshi 3 2 Report of 3 cases

Abe Y[50] 1998 Nihon Kokyuki Gakkai Zasshi 1 1 One case of MALToma diagnosed with flow cytometer analysis, monoclonal gammopathy and Southern blot analysis of the heavy chain of the immunoglobulin gene

Umino T[51] 1993 Nihon Kokyuki Gakkai Zasshi 1 1 A case of PLL diagnosed with: High serum IgG, BAL showing 45% plasma cells and 18% lympocytes, CD19(+), IgG/albumin ratio 13 times higher and IL-6/albumin ratio29 times higher in BAL than serum. The PCR on the DNA extracted from the surgical specimen showed rearrangement of the immunoglobulin heavy chain gene

Zinzani PL [52] 2003 12 MALTomas

Herbert A[53] 1984 Hum Pathol 9 9 The authors claim that histologic evidence of lymph node involvement is unusual even in the presence of mediastinal or pleural infiltration

Davis WB[54] 1987 Chest 1 1 Report of one case of bilateral interstitial infiltrates with lymhocytic alveolitis on the BAL

Pisani RJ[55] 1990 Mayo Clin Proc 1 1 Report of the first case wherein PLL was diagnosed with immunohistologic (less diagnostic for T cell lymphomas) and molecular biologic studies of BAL.

Sprague RI[56] 1989 Chest 1 A case of an elderly female with multiple densities on CXR. Diagnosis was made with transthoracic fine needle aspiration

Julsrud PR[57] 1978 Radiology Pseudolymphoma & lymphocytic interstitial pneumonitis have a different radiographic pattern to lymphocytic lymphoma

Lewis ER[58] 1991 AJR Am J Roentgenol 31 CT findings of pulmonary lymphoma: masslike consolidation (68%), multiple nodules (55%). 2/3 of the patients have more than one type of CT finding simultaneously

Bellotti M[59] 1987 Respiration 5 Report a series of 5 PLL out of 9 lymphomas involving the lung

Kilgore TL[60] 1983 Chest 4 4 cases of endobronchial nHL. The authors claim that all the patients had disseminated disease at the time of endobronchial involvement.

Rose RM[61] 1986 Cancer 3 3 cases of endobronchial nHL. The authors have identified 2 patterns of endobronchial involvement: Type 1 characterized by submucosal infiltrates occurring in the presence of disseminated disease and Type 2 whereby the central airway is involved by a solitary mass in the absence of disease elsewhere.

Oka M[62] 1988 Am Rev Respir Dis 1 A case report, whereby the diagnosis of PLL was made 5 years after initial presentation

[TableWrap ID: T2] Table 2 

Published Studies with large number of patients


Author Year Journal Number of Patients Characteristics Appearance Recurrence Survival
Koss MN[63] 1983 Hum Pathol 161 14% pseudolymphomas 138 nHL. Elderly, mainly asymptomatic Most cases: Solitary nodule or infiltrate Most recurrences occur within 3 years 18 out of 101 patients died from tumor. Pleural effusion was a predictor of mortality

Turner RR[64] 1984 Cancer 47 28 cases of PLL Good prognosis: 1 patient died in 4 years follow up

L Hoste R[65] 1984 Cancer 36 nHL Mean age 53 y. More than 80% of patients >40 y Single lesions 20 cases. Multiple: 16. Unilateral 26, bilateral 10. IE:24, II1E:2, II2E:8, II2EW:2 58% LPI 33% of LPI recur. 50% of non LPI recur. Average time to recurrence:69 months 33% died, most non LPI. No survival difference among cases grouped according to stage(IE Vs II2E). For stage IE LPI group did better. 5 years survival 57%

Kennedy JL[66] 1985 Cancer 64 pts with lymphoid lesions of lung 12 patients with primary lymphoma Heterogenous group of patients Median survival of 117 months if PLL. For Disseminated lymphoma median survival 33 months

Li G[67] 1990 Histopathology 62 cases. All B cell but 2 cases of T-cell lymphoma 43 cases of MALT 32 of the MALTS showed solitary or multiple sharply defined nodules Recurrences in 46% of the MALTs Constitutional symptoms and T cell lymphoma showed a bad prognosis.

Cordier JF[68] 1993 Chest 70 nHL, no mediastinal adenopathy Mean age 58.4 y, M:F 1:1, majority non smokers. 87% Low grade. majority MALTs. 13% high grade Localized opacities 87%. Mass -like appearance 24%, Bilateral disease 21%. Monoclonal gammopathy 30%. Metastasis 7 pts(stomach, bone marrow, spleen, liver) interval between Dx and mets from 10 months to 7 years 69% underwent surgical resection. Overall survival 93.6% at 5 years for low grade L 26% treated with chemotherapy alone

Ferraro P[69] 2000 Annals of Thorac Surg 48 nHL MALTs 73%. Mean age 61.8 years. Symptoms 62.5% of patients, Mass lesion 60%, Bilateral disease 44%. Mediastinal-hilar lymphadenopathy 31%. Pleural effusions 15%. IE: 37 patients, II2E:7, II2EW:3, Stage III:1 Local recurrence 50% Complete surgical resection 40% overall. Incomplete resection in 29 patients (21 patients with bilateral disease) 73% of MALTs had complete resection. Post op Chemo 54%. Five year survival for MALTs 68% and 10 years 53%..

Graham B[70] 2005 Annals of Thorac Surg 18 MALTs 78%. Mean age 66.4 y M:F 1:2 Symptoms 78% of patients, Nodules or Mass lesions 72%, Bilateral disease 39%. Mediastinal-hilar lymphadenopathy 39%. Pleural effusions 22%. IIE (39%) pts. Median time to disease recurrence or death: 6 years 6% died of disease. Five year survival > 80%

Hu YH[71] 2009 Ann Hematol 22 MALTs 54% Nodules or masses 73%. Mediastinal lymphadenopathy MALTs/non-MALTs: 8/80 Patients who had surgery tended to have better survival. Five year survival MALTs/Non-MALTs 91% over 21%.


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