Lymphomatoid granulomatosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Lymphamtoid granulomatosis must be differentiated from Bronchocentric granulomatosis and Churg-Strauss, Necrotizing sarcoid granulomatosis, Wegeners granulomatosis, Hodgkins disease, Non-hodgkin lymphoma, and Nasal angiocentric lymphoma

Differentiating Lymphamatoid granulomatosis from other Diseases

As Lymphamatoid granulomatosis manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtypes pulmonary being the most common. The sub types are the following:[1][2][3][4][5]

  • Cough(non-productive, rarely hemoptysis can occur)[6][7]
  • Dyspnea[8]
  • Chest tightness[9]

Other Symptoms that are asscociated with the pulmonary symptoms are:[9][10] [11]

  • Malaise
  • Weight loss
  • Fatigue

From the symptoms listed above; Lymphamatoid granulomatosis is usually differtiated from the following diseases Bronchocentric granulomatosis and Churg-Strauss, Necrotizing sarcoid granulomatosis, Wegeners granulomatosis, Hodgkins disease, Non-hodgkin lymphoma, and Nasal angiocentric lymphoma.[12][13][14]

In contrast, CNS lymphamatoid granulomatosis must be differentiated from other diseases that cause:[15][16][17][18]

  • Headaches
  • Seizures
  • Hemiparesis
  • Ataxia

The differentials are the following CVA, Brain tumors or CNS lymphoma and Parkinsonism.[19]

Finally Cutaneous Lymphamatoid granulomatosis must also be differtiated from other diseases that cause:[18][20][21]

  • Erythematous rash
  • Macules
  • Papules
  • Plaques
  • Subcutaneous nodules
  • Larger ulcerated nodules

The differentials are the following Dermatomyositis, and Psoriasis

Differentiating Lymphamatoid Granulomatosis

On the basis of Cough, Dyspnea, and Chest tightness, Lymphamatoid granulomatosis must be differentiated from Bronchocentric granulomatosis and Churg-Strauss, Necrotizing sarcoid granulomatosis, Wegeners granulomatosis, Hodgkins disease, Non-hodgkin lymphoma, and Nasal angiocentric lymphoma.[12][13][14]{| |- style="background: #4479BA; color: #FFFFFF; text-align: center;" ! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Diseases | colspan="6" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Clinical manifestations ! colspan="7" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para-clinical findings | colspan="1" rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard ! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Additional findings |- | colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptoms ! colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical examination |- ! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings ! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging ! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology |- ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Cough ! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Dyspnea ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Chest tightness ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Auscultation ! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;" | ! style="background: #4479BA; color: #FFFFFF; text-align: center;" | ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab findings ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab 2 ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab 3 ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |X-ray ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |CT scan ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging 3 |- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Lymphmatoid granulomatosis | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" |Wheezing

Rales

Rhonchi | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |EBV infused B-cells on blood scan | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Dense, large, mass like infiltrate and bilateral nodular disease.

| style="background: #F5F5F5; padding: 5px;" |Poorly defined nodular peribronchovascular infiltrates with air-bronchograms. | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

    • Nodular and diffuse lymphoid infiltrates along lymphatics and bronchovascular bundles
    • Centers of nodules have large vessels with lymphatic infiltration

| style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

    • Predisposing factor is primary or secondary immunodeficiency states
    • Patients may have fever of unknown origin, hemoptysis, history of multiple skin or other biopsies without diagnosis

|- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Churg-Strauss syndrome | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" |Wheezing

Rales

Rhonchi | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Greater than 50% have positive ANCA, often antimyeloperoxidase
  • Eosinophilia

| style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |Pulmonary infiltrates: Typically, these are transient patchy alveolar infiltrates. | style="background: #F5F5F5; padding: 5px;" |

  • Subpleural airspace consolidation
  • Enlarged hilar or mediastinal lymph nodes

| style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Lung and extrapulmonary sites with eosinophilic infiltrate,
  • Granulomatous reaction near small arteries, eosinophilic vasculitis
  • May have edema, lymphocytes, sarcoid-like granulomas.

| style="background: #F5F5F5; padding: 5px;" | + P-ANCA | style="background: #F5F5F5; padding: 5px;" |

  • Very rare

|- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Necrotizing sarcoid granulomatosis | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" | - | style="background: #F5F5F5; padding: 5px;" |Wheezing | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |Increased levels of ACE in the blood | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |Hilar adenopathy | style="background: #F5F5F5; padding: 5px;" |bihilar lymphadenopathy and reticulonodular infiltrates

| style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Inflammatory and granulomatous reactions
  • Resembling lymphoma and atypia
  • Dense, noncaseating granulomatous infiltrate
  • Also Schaumann bodies

| style="background: #F5F5F5; padding: 5px;" |High levels of ACE in blood | style="background: #F5F5F5; padding: 5px;" |

  • Affects skin, lymph nodes and organs
  • Diagnosis of exclusion
  • Patients often have anergy to delayed hypersensitivity tests

|- style="background: #4479BA; color: #FFFFFF; text-align: center;" !Diseases !Cough ! colspan="1" rowspan="1" |Dyspnea !Chest thightness !Auscultation ! colspan="1" rowspan="1" | ! !Lab findings !Lab 2 !Lab 3 !X-ray !CT scan !Imaging 3 !Histopathology |Gold standard !Additional findings |- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Wegeners granulomatosis | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" | + | style="background: #F5F5F5; padding: 5px;" | - | style="background: #F5F5F5; padding: 5px;" |Wheezing | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |C- ANCA

Urinalysis:

Hematuria

Red cell casts

Biopsy: Granulomatous inflmmation within the arterial wall or in the perivascular area | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Nodules,
  • Infiltrates or
  • Cavities

| style="background: #F5F5F5; padding: 5px;" |Pulmonary nodules with or without cavitation and airspace consolidation | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

    • Liquefactive or coagulative necrosis in lungs with huge number of eosinophils, and granulomas; surrounded by histiocytes and giant cells with central necrosis
    • Destructive leukocytic angiitis of arteries and veins

| style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • p-ANCA: perinuclear staining, directed against myeloperoxidase, is usually negative, but positive in microscopic polyarteritis, inflammatory bowel disease, crescentic glomerulonephritis

|- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Hodgkin disease | style="background: #F5F5F5; padding: 5px;" | - | style="background: #F5F5F5; padding: 5px;" | - | style="background: #F5F5F5; padding: 5px;" | - | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Contains a small number of the characteristic neoplastic cells (Hodgkin and Reed-Sternberg cells or lymphocyte predominant cells) within a background rich in inflammatory cells

| style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Parenchymal lung involvement occurs in 1/3 of patients with Hodgkin
  • Almost all have associated hilar or mediastinal adenopathy

| style="background: #F5F5F5; padding: 5px;" |Massive mediastinal soft tissue masses consistent with lymphoma | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Neoplastic cells are Hodgkin and Reed-Sternberg (HRS) cells
  • Effaced lymph node with variable number of HRS cells in a background of inflammatory cells

| style="background: #F5F5F5; padding: 5px;" |Reed Sternberg cells | style="background: #F5F5F5; padding: 5px;" |Development of Hodgkin's disease may in some patients be preceded by enhanced activation of Epstein–Barr virus |- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Non-hodgkin lymphoma | style="background: #F5F5F5; padding: 5px;" | - | style="background: #F5F5F5; padding: 5px;" | - | style="background: #F5F5F5; padding: 5px;" | - | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |Can be caused by; EBV

HIV

Hep C

HTLV

Lymphomatous appearing B and T cells( condition arises from B and T cells) | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |Mediastinal widening due to grossly enlarged right paratracheal and left paratracheal nodes. | style="background: #F5F5F5; padding: 5px;" |Mediastinum can show enlarged tracheobronchial and subcarinal nodes. small bilateral pleural effusion can be seen | style="background: #F5F5F5; padding: 5px;" | | style="background: #F5F5F5; padding: 5px;" |

  • Sensitivity and specificity of diagnosis with fine needle aspiration increases with use of flow cytometry

| style="background: #F5F5F5; padding: 5px;" |Pop corn cells in NLPHL | style="background: #F5F5F5; padding: 5px;" |Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness |}

References

  1. ↑ Roschewski M, Wilson WH (2012). "Lymphomatoid granulomatosis". Cancer J. 18 (5): 469–74. doi:10.1097/PPO.0b013e31826c5e19. PMID 23006954.
  2. ↑ Fernandez-Alvarez R, Gonzalez M, Fernandez A, Gonzalez-Rodriguez A, Sancho J, Dominguez F; et al. (2014). "Lymphomatoid granulomatosis of central nervous system and lung driven by epstein barr virus proliferation: successful treatment with rituximab-containing chemotherapy". Mediterr J Hematol Infect Dis. 6 (1): e2014017. doi:10.4084/MJHID.2014.017. PMC 3965717. PMID 24678394.
  3. ↑ Miloslavsky EM, Stone JH, Unizony SH (2015). "Challenging mimickers of primary systemic vasculitis". Rheum Dis Clin North Am. 41 (1): 141–60, ix. doi:10.1016/j.rdc.2014.09.011. PMID 25399945.
  4. ↑ Tagliavini E, Rossi G, Valli R, Zanelli M, Cadioli A, Mengoli MC; et al. (2013). "Lymphomatoid granulomatosis: a practical review for pathologists dealing with this rare pulmonary lymphoproliferative process". Pathologica. 105 (4): 111–6. PMID 24466760.
  5. ↑ Fauci AS, Haynes BF, Costa J, Katz P, Wolff SM (1982). "Lymphomatoid Granulomatosis. Prospective clinical and therapeutic experience over 10 years". N Engl J Med. 306 (2): 68–74. doi:10.1056/NEJM198201143060203. PMID 7053488.
  6. ↑ Xu B, Liu H, Wang B, Zhang H, Wu H, Jin R; et al. (2015). "Fever, Dry Cough and Exertional Dyspnea: Pulmonary Lymphomatoid Granulomatosis Masquerading as Pneumonia, Granulomatosis with Polyangiitis and Infectious Mononucleosis". Intern Med. 54 (23): 3045–9. doi:10.2169/internalmedicine.54.4822. PMID 26631890.
  7. ↑ Ameli F, Ghafourian F, Masir N (2014). "Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report". J Med Case Rep. 8: 288. doi:10.1186/1752-1947-8-288. PMC 4150421. PMID 25163591.
  8. ↑ Olusina D, Ezemba N, Nzegwu MA (2011). "Pulmonary Lymphomatoid Granulomatosis: Report of A Case and Review of Literature". Niger Med J. 52 (1): 60–63. PMC 3180752. PMID 21968985.
  9. ↑ 9.0 9.1 O'Brien S, Schmidt P (2016). "Lymphomatoid Granulomatosis with Paraneoplastic Polymyositis: A Rare Malignancy with Rare Complication". Case Rep Rheumatol. 2016: 8242597. doi:10.1155/2016/8242597. PMC 4757691. PMID 26966605.
  10. ↑ Alinari L, Pant S, McNamara K, Kalmar JR, Marsh W, Allen CM; et al. (2012). "Lymphomatoid granulomatosis presenting with gingival involvement in an immune competent elderly male". Head Neck Pathol. 6 (4): 496–501. doi:10.1007/s12105-012-0378-z. PMC 3500898. PMID 22711054.
  11. ↑ Alexandra G, Claudia G (2018). "Lymphomatoid granulomatosis mimicking cancer and sarcoidosis". Ann Hematol. doi:10.1007/s00277-018-3505-4. PMID 30288554.
  12. ↑ 12.0 12.1 Bohle M, Rasche K, Müller KM, Schultze-Werninghaus G, Fisseler-Eckhoff A (1999). "[Lymphomatoid granulomatosis: differential diagnosis and therapy]". Med Klin (Munich). 94 (9): 513–9. PMID 10544614.
  13. ↑ 13.0 13.1 Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMC 5922622. PMID doi.org/10.1053/stcs.2002.34450 Check |pmid= value (help).
  14. ↑ 14.0 14.1 Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMC 5922622. PMID https://doi.org/10.1007/s00247-014-3233-4 Check |pmid= value (help).
  15. ↑ Kim JY, Jung KC, Park SH, Choe JY, Kim JE (2018). "Primary lymphomatoid granulomatosis in the central nervous system: A report of three cases". Neuropathology. doi:10.1111/neup.12467. PMID 29635846.
  16. ↑ Kano Y, Kodaira M, Ushiki A, Kosaka M, Yamada M, Shingu K; et al. (2017). "The Complete Remission of Acquired Immunodeficiency Syndrome-associated Isolated Central Nervous System Lymphomatoid Granulomatosis: A Case Report and Review of the Literature". Intern Med. 56 (18): 2497–2501. doi:10.2169/internalmedicine.8776-16. PMC 5643181. PMID 28824078.
  17. ↑ Quinones E, Potes LI, Silva N, Lobato-Polo J (2016). "Lymphomatoid granulomatosis of the brain: A case report". Surg Neurol Int. 7 (Suppl 23): S612–6. doi:10.4103/2152-7806.189732. PMC 5025951. PMID 27656321.
  18. ↑ 18.0 18.1 Halvani A, Owlia MB, Sami R (2010). "Lymphomatoid granulomatosis with splenomegaly and pancytopenia". Zhongguo Fei Ai Za Zhi. 13 (1): 84–6. doi:10.3779/j.issn.1009-3419.2010.01.17. PMC 6000673. PMID 20672711.
  19. ↑ Sohn EH, Song CJ, Lee HJ, Kim S, Kim JM, Lee AY (2007). "Central nervous system lymphomatoid granulomatosis presenting with parkinsonism". J Clin Neurol. 3 (2): 108–11. doi:10.3988/jcn.2007.3.2.108. PMC 2686859. PMID 19513302.
  20. ↑ Rysgaard CD, Stone MS (2015). "Lymphomatoid granulomatosis presenting with cutaneous involvement: a case report and review of the literature". J Cutan Pathol. 42 (3): 188–93. doi:10.1111/cup.12402. PMID 25355540.
  21. ↑ Gangar P, Venkatarajan S (2015). "Granulomatous Lymphoproliferative Disorders: Granulomatous Slack Skin and Lymphomatoid Granulomatosis". Dermatol Clin. 33 (3): 489–96. doi:10.1016/j.det.2015.03.013. PMID 26143428.

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