Lymphomatoid granulomatosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kamal Akbar, M.D.[2]
Overview
Lymphomatoid granulomatosis arises from T cells infused with EBV, which are lymphoid cells that are normally involved in Immunity.As a result patients typically resent with pulmonary symptoms (cough, dyspnea, chest tightness).Patients with lymphomatoid granulomatosis tend to have low CD4 counts usually due to infection (EBV, hep c, and hiv) and/or immunospression( immunosuppressive drugs, and Inherited immunodeficiency diseases).On microscopic pathology inflammation of micro vessels are seen or angitis is seen and t cells containing EBV.On gross pathology nodules are seen mostly in the lung.
Pathophysiology
Physiology
- The normal physiology of cell mediated immunity can be understood as follows:
- Historically, the immune system was divided into two branches:
- Humoral immunity, for which the defending function of immunization could be seen in the humor (cell-free bodily fluid or serum)
- Cellular immunity or Cell mediated immunity , for which the defending function of immunization was associated with cells. The cell involved in cell mediated immunity are the following:
- CD4 cells or Helper T cells provide defense against varying pathogenic organisms.
- Naive T cells
- Mature T cells that have yet to come upon an antigen, and are transformed into activated effector T cells after coming across an antigen-presenting cells (APCs)
- These APCs, are the following
- The cells listed above in some cases, pack antigenic peptides onto the MHC of the cell, in turn introducing the peptide to receptors on T cells. The most important of these APCs are highly specialized dendritic cells; conceivably operating solely to ingest and present antigens.[1]
Pathogenesis
- It is understood that Lymphomatoid granulomatosis is seen in extranodal sites, most commonly the lung
- Other recurrent sites of involvement include the following:
- Kidney
- Skin
- Central nervous system
- Liver
- The pattern of necrosis in both Lymphomatoid granulomatosis and T/Natural killer cell lymphoma are very similar, accentuating the probable importance of EBV in interceding the vascular damage
- Recent studies shows that the chemokines IP-10 and monoclonal immunoglobilins are indicated in the pathogenesis of the vascular damage
- Although the most common infiltrating cells are T cells, the T cell receptor genes are not clonally rearranged. However, by VDJ polymerase chain reaction, approximately 60% of cases contain clonal rearrangements
- EBV sequences can be confined to B cells and are clonal in most cases
- Most patients with Lymphomatoid granulomatosis carefully evaluated clinically have irregularities in there cytotoxic T cell function and low levels of CD8+ T cells[2][3]
Other systems of the body which are affected in Lymphomatoid granulomatosis include:[4]
Gross Pathology
On gross pathology, the following is seen:[9]
- Lung nodules up to 10 cm with central necrosis and cavitation[11][12]
- 15% of patients with skin lesions have indurated and atrophic plaques[13][14]
Microscopic Pathology
On microscopic histopathological analysis, the presence of an angiocentric and angiodestructive accumulation of differing numbers of T cells with varying numbers of atypical clonal EBV-positive B cells in a polymorphous inflammatory background is seen in Lymphomatoid granulomatosis. This is what is seen in the different organ systems that Lymphomatoid granulomatosis affects:[15][12]
- Lung:
- Nodular and disseminated lymphoid infiltrates alongside lymphatics and bronchovascular bundles[16]
- Centers of nodules have large vessels with lymphatic infiltration[16]
- Typically high grade
- Small lymphocytes, plasma cells and histiocytes are also present, seldomly accompanied by neutrophils, granulomas are mostly seen with cutaneous involvement[17]
- Skin:
- Usually multiple erythematous dermal papules or subcutaneous nodules with an angiocentric lymphohistiocytic infiltrate of CD4+ T cells and angiodestruction, necrosis, panniculitis, atypia[18]
- Grading:[9][15] Relates to the proportion of EBV+ B cells relative to the reactive background lymphocytes
- Grade 1:
- infrequent EBV positive cells (< 5/HPF)
- No large atypical cells
- Small amount of necrosis
- Some cases resolve immediately
- Grade 2:
- EBV positive large lymphoid cells or immunoblasts (5 - 50/HPF)
- Intermittent large atypical cells
- Modest amount of necrosis
- Some cases spontaneously resolve
- Grade 3:
- large atypical CD20+ B cells with extensive necrosis and > 50/HPF EBV positive cells
- Prevalent population of large atypical cells
- May be coalescent
- Diffuse necrosis
- Grade 1:
References
- ↑ Denburg JA, Bienenstock J (March 1979). "Physiology of the immune response". Can Fam Physician. 25: 301–7. PMC 2382958. PMID 21297689.
- ↑ Jaffe ES, Wilson WH (1997). "Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications". Cancer Surv. 30: 233–48. PMID 9547995.
- ↑ 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/10.1016/S0046-8177(72)80005-4 Check
|pmid=value (help). - ↑ Hussein MR (2013). "Atypical lymphoid proliferations: the pathologist's viewpoint". Expert Rev Hematol. 6 (2): 139–53. doi:10.1586/ehm.13.4. PMID 23547864.
- ↑ Ankita G, Shashi D (2016). "Pulmonary Lymphomatoid Granulomatosis- a Case Report with Review of Literature". Indian J Surg Oncol. 7 (4): 484–487. doi:10.1007/s13193-016-0525-1. PMC 5097759. PMID 27872542.
- ↑ Piña-Oviedo S, Weissferdt A, Kalhor N, Moran CA (2015). "Primary Pulmonary Lymphomas". Adv Anat Pathol. 22 (6): 355–75. doi:10.1097/PAP.0000000000000090. PMID 26452211.
- ↑ Sugita Y, Muta H, Ohshima K, Morioka M, Tsukamoto Y, Takahashi H; et al. (2016). "Primary central nervous system lymphomas and related diseases: Pathological characteristics and discussion of the differential diagnosis". Neuropathology. 36 (4): 313–24. doi:10.1111/neup.12276. PMID 26607855.
- ↑ Kubota M, Taniguchi M, Tobisawa S, Nakata Y, Nakaya M, Tamogami H; et al. (2017). "T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Presented as T-Lymphoid Hyperplasia Involving the Central Nervous System". Cureus. 9 (3): e1119. doi:10.7759/cureus.1119. PMC 5406172. PMID 28451478.
- ↑ 9.0 9.1 9.2 Beaty MW, Toro J, Sorbara L, Stern JB, Pittaluga S, Raffeld M; et al. (2001). "Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features". Am J Surg Pathol. 25 (9): 1111–20. PMID 11688570.
- ↑ 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.
- ↑ Bartosik W, Raza A, Kalimuthu S, Fabre A (2012). "Pulmonary lymphomatoid granulomatosis mimicking lung cancer". Interact Cardiovasc Thorac Surg. 14 (5): 662–4. doi:10.1093/icvts/ivr083. PMC 3329320. PMID 22361129.
- ↑ 12.0 12.1 Colby TV (2012). "Current histological diagnosis of lymphomatoid granulomatosis". Mod Pathol. 25 Suppl 1: S39–42. doi:10.1038/modpathol.2011.149. PMID 22214969.
- ↑ Fischer R, Shaath T, Meade C, Fraga GR, Rajpara A (2014). "An eschar and violaceous nodules as the presenting signs of lymphomatoid granulomatosis". Dermatol Online J. 20 (11). PMID 25419752.
- ↑ Shaigany S, Weitz NA, Husain S, Geskin L, Grossman ME (2015). "A case of lymphomatoid granulomatosis presenting with cutaneous lesions". JAAD Case Rep. 1 (4): 234–7. doi:10.1016/j.jdcr.2015.05.008. PMC 4808726. PMID 27051739.
- ↑ 15.0 15.1 Guinee DG, Perkins SL, Travis WD, Holden JA, Tripp SR, Koss MN (1998). "Proliferation and cellular phenotype in lymphomatoid granulomatosis: implications of a higher proliferation index in B cells". Am J Surg Pathol. 22 (9): 1093–100. PMID 9737242.
- ↑ 16.0 16.1 Hare SS, Souza CA, Bain G, Seely JM, Gomes MM; et al. (2012). "The radiological spectrum of pulmonary lymphoproliferative disease". Br J Radiol. 85 (1015): 848–64. doi:10.1259/bjr/16420165. PMC 3474050. PMID 22745203.
- ↑ Mukhopadhyay S, Gal AA (2010). "Granulomatous lung disease: an approach to the differential diagnosis". Arch Pathol Lab Med. 134 (5): 667–90. doi:10.1043/1543-2165-134.5.667. PMID 20441499.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMC 5922622. PMID doi:10.1001/archderm.1996.03890360054010 Check
|pmid=value (help).