Lymphoproliferative Disorders of the Lung

Prof. Dr. Aydanur Kargı

Dokuz Eylül Üniversitesi Tıp Fakültesi Patoloji ABD

Pulmonary Lymphoid Tissue

• Peribronchial LNs present till 4th order bronchi• Distal bronchi and brochioles may have BALT• 82% of smokers, 14 % of non-smokers have

BALT. • Intrapulmonary LN:, 8-46 % of well-

circumscribed, peripheral nodules less than 12mm shown by CT are IPLN.

*CT findings may resemble those of lung cancer Yokomise H. et al. Importance of intrapulmonary lymph nodes in the

differential diagnoses of small pulmonary nodular shadows. Chest 1998; 113:703-06

Pulmonary Lymphoproliferative Lesions

Benign-reactive: Associated with systemic diseases or pulmonary chronic

inflamations *When they occur, patients usually have an underlying

systemic disease. Uncommonly, the lung may be the only organ initially involved.

Potantially malignant: Lenfomatoid granulomatosisMalignant: Secondary ≥ Primary Secondary: a)spread by circulation b)by direct invasion of mediastinal lymphoma

BENİGN LYMPHOİD PROLİFERATİONS

Diffuse lymphoid proliferations*Follicular bronchitis-bronchiolitis (FB)*Lymphocytic Intertisial Pneumonia(LİP)Localized lymphoid proliferations*Nodular lymphoid hyperplasia ( Pseudolymphoma) Castleman disease Inflamatuar myofibroblastic tumor????? Langerhans cell histiositosis??

FB-LIP

• Associated diseases Collagen vascular diseases (RA) Otoimmune diseases (Sjögren ) Viral infections (EBV, HIV..) Immün deficiencies (congenital, acquired): LIP is now

part of case definition of AIDS in children under 13 years of age.

* Idiopathic, LIP (ATS/ERS:Intertisial pneumonia)

Follicular Bronchitis-Bronchiolitis

Non spesific airway inflamations:

• Chronic airway infections, bronchiectesia

• Obstruction of bronchi and bronchioles

• Asthma, hypersensitivity reactions

• Chronic obstructive lung diseases

• Cystic fibrosis

FB- LIP, NLH

FB-LIP: Diffuse, bilateral

NLH: Localized, single or more than one

• Histopathology

lymphoid folliculles,

B and T lymphocytes, polyclonal plasma cells

FB

LIP

NLH

BCL-2

CD20CD3

FB-LIP

• Clinical, radiologic and pathologic findings of FB-LIP may overlap.• 5th-7th decades...• 25% of LIP patients have Sjögren syndrome, 0.9% of SS have LIP.• Symptoms and signs of diffuse interstisial lung disease and underlying diseases.• Radiologic findings are nonspecific.Diffuse reticular and nodular opacities..• CT: ground glass-poorly defined centilobular nodules• HRCT: thickening of bronchovascular interstisium and alveolar septae.• Lab: disproteinemi seen in 60% of patients.Decreased lung volume and diffusion

capacity.• Treatment is with steroids. Response is variable. 1/3-1/2 of patients die in 5

years(immunsupression related)• 5% may develop lymphoma.

*Koss MN. Malignant and Benign Lymphoid lesions of the lung. Ann Diag Pathol. 2004; 8(3):167-87

Idiophatic Lymphocytic Interstitial Pneumonia

• 1969…Liebow…interstitial pneumonia• 1980…lymphoma?• 2001…ATS/ERS, Idiophatic LIP Differential diagnoses: NSIP patern.. (reaction

patern seen in the lungs of adult AIDS)

Colby TV. Pulmonary lymphomas:Current concepts. Hum Pathol. 1983;14(10):884-887

NSIP

LIP

Nodular Lymphoid Hyperplasia(pseudolymphoma)

• 1963..Salzstein…pseudolymphoma• 1980…lymphoma??• 1983..Kradin ve Mark…NLH• 2000..Abbondanzo et al*. 14 cases

*not associated with any known disease *median:65 years, 71% incidental lesions *usually solitary, occasionally multiple nodules, 2-4cm * has to be differentiated from MALT lymphoma!!! * surgical excision is adequate.

Abbondanzo SL,et al. Noduler lymphoid hyperplasia of the lung:a clinicopathologic study of 14 cases. Am J Surg Pathol 2000; 24:587-97.

Primary Pulmonary Lymphomas

• No extra pulmonary lymphoma present at the time of, or within the next 3 months following diagnoses

• 0.5-1% of all pulmonary neoplasias

• 70-90 % of all primary lung lymphomas are extranodal marginal zon lymphoma (MALT lymphoma).

• 15-20 % of all MALT lymphomas are pulmonary MALT lymphoma

• Other B cell, T/NK cell NHLs and HL are rare

Pulmonary MALT type MZ- B cell lymphoma

• Pathogenesis:Antigenic stimuli (CVD, OID)

• Immunoprofile:CD20+, CD79a+, CD43+/-

CD5,CD23, CD10,cyclinD1-

• Trisomi 3 and 18.... (%40)

• t(11;18)(q21;q21)..(%41): plasmacytic differentiation and otoimmün disease not present.

Pulmonary MALT Lymphoma• It is seen more often in women and in 6th. decade.• Cough, dispnea, hemoptisia, chest pain.. 1/3-1/2 patients are asemptomatic… Chest

x-ray shows solitary nodules less than 5cm.Fever, night sweats, weight lost not frequent.

• Lab.findings are non-contributory.• BAL: There may be over 10% B cell. It is necessary to show clonality by MG.

Diagnostic value of BAL is unknown.• Up to 40% of patients have hilar LN involvement.• Prognosis is good, stays localized for many years, survival for 5 and 10 years: 84%

and 88 %.(10 years:72%)• 50% of cases show recurrens in lungs or extrapulmoner mucosal sites such as

stomach and salivary glands in 2 years.• Adverse prognostic factors: plevral efusion and presence of amyloid in tumor,

serumda ß2 microglobulin• Treatment: localized….surgary diffuse, bilateral….chemotherapy

Koss MN. Malignant and benign lymphoid lesions of the lung. Ann Diag Pathol 2004; 8(3):167-87.

CD20

KERATİN

KERATİN

MALT Lymphoma –Differential Diagnoses

• Other B cell low grade small lymphocytic neoplasias.• Benign lymphoid hyperplasias:FB-LİP, NLH: Molecular Genetic studies? Clonality ??? LİP olgularında monoklonalite + ???

• TANI:TTİB, TBİB, VAT-Açık AC biop.

Diff LE

(Foll Br)

LİP NLH MALT

Structure Diffüz,bronş

bronşiol

İlişkili

Alveol septalarında

diffüz

İyi sınırlı, lokalize

Lokalize,

İnfiltratif,

invaziv

Cellüler

composition

Poliklonal

Lenf-plazmosit

Poliklonal

Lenf-plazmosit

Poliklonal

Lenf-plazmosit

MonoclonalLenf-plazmosit

Sentrosit benzeri hc

Monositoid hc

Transforme hc

LEL +/- +/- - prominent

Germinal centre + + + +

Pleura- bronchial cartilage

invasion

- - - +++

Lymphomatoid Granulomatosis

 

   1972 Liebow..........pulm. vasc. ve granulomatosis

1994 REAL............angiosentric T cell lymphoma

2001 WHO............ diffuse, large B cell NHL variant?

 

Lipford....1988.....histologic grading???

Lymphomatoid Granulomatosis

• EBV infected neoplastic B cells, numerous T-lymphocytes and histiocytes

• Middle aged adults, Idiophatic or in immunsupressed patients, involvement of lungs, CNS, kidneys, upper respir. tract

• Up to 70% of patients show bilateral, peripheral up to 9cm nodules. Other x-ray patterns:diffuse reticulonodular or alveoler infiltration or soliter mass

• Open lung biopsy for diagnoses.• Grade 1 and 2 have better prognoses, grade 3 behaves like high grade

lymphoma

Koss MN. Malignant and benign lymphoid lesions of the lung. Ann Diag Pathol. 2004; 8(3): 167-187.

CD68

CD3

CD3

CD20

Secondary Pulmonary Lymphomas

• NHL: 21%, HL:17%*

• NHL:Diffuse, large B cell

Small lymphocytic lymphoma/CLL

Periferal T cell.. 26%, most often MF

*Lösemiler

*Costa MBG et al. Histologic patterns of lung infiltration of B-cell, T-cell, and Hodgkin lymphomas. Am J Clin Pathol 2004; 121: 718-726.

Diagnoses

Secondary>>>primary• Broncoscophic bronchial or transbronchial

parenchymal bx.?• Transtorasic needle biopsy? • Pleural biopsy, efusion cytology • BAL??? FC:İmmunophenotyping?

PCR: Molecular genetic analysis

Primary: Open lung biopsy!!!!!

TTNB-MALT lenfoma

T-lenfoblastik lenfoma

CD3 • TdT

• CD3

CD20

CD5

CML

MP

Conclusion

• In the lungs, secondary lymphoproliferative disease involvement is seen much more frequently than primary lymphomas.

• Bronchoscopic biopsy, pleural biopsy and cytology are valuable in diagnoses of secondary disease.

• Open lung biopsy is valuable in differentiation of MALT lymphoma from benign reactive lymphoid proliferations. Molecular genetic studies may be needed.

HL

HL

Lenfoplasmosytic lymphoma

LAMBDA