Lymphomatoid granulomatosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Lymphomatoid granulomatosis arises from T cells infused with EBV, which are Lymphoid cells that are normally involved in Immunity.
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) and cellular immunity, for which the defending function of immunization was associated with cells. 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, are transformed into activated effector T cells after coming across an antigen-presenting cells (APCs). These APCs, such as macrophages, dendritic cells, and B cells 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 kidney, skin, central nervous system and liver. The pattern of necrosis in both Lymphomatoid granulomatosis and T/Natural killer cell lymphoma is very similar, accentuating the probable importance of EBV in interceding the vascular damage. Recent studies shows that the chemokines IP-10 and Monoclonal immunoglobilins 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
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 Lympahtoid granulomatosis affects:[13][12]
- Lung:
- Nodular and disseminated lymphoid infiltrates alongside lymphatics and bronchovascular bundles
- Centers of nodules have large vessels with lymphatic infiltration
- Typically high grade
- Small lymphocytes, plasma cells and histiocytes are also present, seldomly accompanied by neutrophils, granulomas are mostly seen with cutaneous involvement
- Skin:
- Usually multiple erythematous dermal papules or subcutaneous nodules with an angiocentric lymphohistiocytic infiltrate of CD4+ T cells and angiodestruction, necrosis,
panniculitis, atypia
- Grading:
- Relates to the proportion of EBV+ B cells relative to the reactive background lymphocytes
- Grade 1 - infrequent EBV positive cells (< 5/HPF)
- Grade 2 - EBV positive large lymphoid cells or immunoblasts (5 - 50/HPF)
- Grade 3 - large atypical CD20+ B cells with extensive necrosis and > 50/HPF EBV positive cells
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 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.
- ↑ 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.