Lymphoproliferative Disorders of the Lung Prof. Dr. Aydanur Kargı Dokuz Eylül Üniversitesi Tıp...

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