Table of Contents
Clofazimine induced changes | Hyaline deposits | Infarction | Lymphedema | Mantle cell / marginal zone hyperplasia | Monocytoid B cell hyperplasia | Plasmacytosis | Polykaryocytes | Sinus histiocytosis | Board review style question #1 | Board review style answer #1Cite this page: Balakrishna J, Sharabi A, DePond W. Other nonspecific findings. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphnodesothernonspecific.html. Accessed January 4th, 2025.
Clofazimine induced changes
Definition / general
- Clofazimine induced crystal storing histiocytosis
ICD coding
- ICD-10: R59.9 - enlarged lymph nodes, unspecified
Epidemiology
- Rare condition in patients taking clofazimine, an antileprosy medication
Sites
- Most commonly subcutaneous tissue, spleen, lymph nodes, liver, lung and gastrointestinal tract
Clinical features
- Red discoloration of skin and other tissues, mass formation, lymphadenopathy
Diagnosis
- History of clofazimine intake, biopsy
Radiology description
- Enlarged lymph nodes, particularly intra-abdominal lymph nodes
Prognostic factors
- Extent of involvement
Case reports
- 32 year old man with chronic abdominal pain (Am J Surg Pathol 2000;24:129)
- 41 year old leprosy patient with abdominal pain (Pathology 1993;25:24)
- 44 year old woman with adenocarcinoma of colon and crystal storing histiocytosis (Lepr Rev 2004;75:171)
Treatment
- Excision of affected lymph node
- Cessation of treatment apparently does not reverse the process
Gross description
- Enlarged lymph node with light brown to dark red discoloration
- Fixative and solutions used for processing the specimen turn red with the crystals dissolving in them
Microscopic (histologic) description
- Marked interfollicular plasmacytosis and histiocytes containing crystals in their cytoplasm, which are elongated with irregular edges, some forming bundles
- Crystals are typically deep red, but depending on the fixative and processing can be clear and colorless (crystals dissolve in alcohol)
- Crystals show bright red birefringence if polarized
- They can be seen in extra and intracellular locations
Positive stains
- Plasma cells are highlighted by CD138 and are polyclonal by kappa and lambda light chain stains
- Lymphocytes are mixed B and T cells and histiocytes show positive staining with CD68 and CD163
Negative stains
- Crystals are negative for PAS and immunoglobulin heavy and light chains
Electron microscopy description
- Transmission electron microscopy shows the empty spaces which crystals have been occupying
- Crystals show some osmiophilic material which appear to be granular or multivesicular bodies
- Upon higher magnification, these crystals show a multilamellar core or a lattice with elements spaced periodically
Electron microscopy images
Images hosted on other servers:
Molecular / cytogenetics description
- No clonal populations of cells
Differential diagnosis
- Crystal storing histiocytosis with immunoglobulin crystals:
- Usually associated with a lymphoid or plasma cell neoplasm
- Fungi
- Parasites
Additional references
- PLoS One 2012;7:e47494, Head Neck Pathol 2012;6:111, Antimicrob Agents Chemother 2016;60:3470, Antimicrob Agents Chemother 2011;55;4000, J Pharmac Sciences 2017;106:1162
Board review style question #1
Hyaline deposits
Definition / general
- Also called proteinaceous lymphadenopathy
- Often present in stroma of pelvic or abdominal nodes
- Nonspecific finding
- Increases with age (Am J Pathol 1975;78:7, Histol Histopathol 2003;18:1169)
- May reduce nodal function
- Associated with
- Rheumatoid arthritis and systemic sclerosis (J Clin Pathol 1994;47:138, Br J Rheumatol 1995;34:1087)
- Hypergammaglobulinemia (Arch Pathol Lab Med 1990;114:34, Am J Surg Pathol 1979;3:137)
- Posttreatment changes for carcinoma (Histopathology 1996;29:63)
- May calcify
Microscopic (histologic) description
- Extracellular eosinophilic material resembling amyloid but Congo Red negative
- Hyaline sclerosis of small and midsized vessels of lymph nodes and organs (Blood 1995;86:1159)
Positive stains
- Immunoglobulins
Negative stains
Differential diagnosis
Infarction
Definition / general
- Uncommon
- Associated with fever, pain and lymphadenopathy (Am J Clin Pathol 1980;74:687)
- Causes:
- Lymphoma
- Melanoma or granulocytic sarcoma (APMIS 2003;111:1133)
- Venous thrombosis
- Arterial occlusion in vasculitis (polyarteritis nodosa)
- Emboli (cholesterol) (Hum Pathol 1978;9:597)
- Heart lung transplantation (J Thorac Cardiovasc Surg 1990;99:861)
- Fine needle aspiration (J Clin Pathol 1982;35:855, Diagn Cytopathol 2001;25:104)
- Mediastinoscopy (Ann Thorac Surg 1989;48:247)
- Gold injection (J Clin Pathol 2001;54:562)
- Dengue fever with DIC (BMC Clin Pathol 2005;5:11)
- Infectious mononucleosis (Int J Surg Pathol 2002;10:223)
- Parvovirus B19
- Intestinal volvulus
- Examine node carefully (possibly with levels or immunohistochemistry) and follow patient to rule out lymphoma or other malignancies (Histopathology 1986;10:571, Indian J Pathol Microbiol 2005;48:510)
Microscopic (histologic) description
- Extensive necrosis with perinodal inflammation and granulation tissue
- May retain a rim of viable lymphatic tissue
- Reticulin architecture is retained
Microscopic (histologic) images
Images hosted on other servers:
Superficial lymph nodes:
Immunohistochemistry
- Tumor cells may stain with traditional markers (keratin, S100), even if remaining node is necrotic but be cautious (Arch Pathol Lab Med 2003;127:60, Arch Pathol Lab Med 2003;127:922)
Differential diagnosis
- Granulomatous inflammation
- Infectious mononucleosis
- Kikuchi disease
- Malignancy: lymphoma or melanoma
- Mucocutaneous lymph node syndrome
Additional references
Lymphedema
Definition / general
- Either congenital, infectious, obstructive, traumatic or idiopathic
- Congenital: also called Milroy disease (primary hereditary lymphedema), autosomal dominant (OMIM: Lymphedema, Hereditary, IA; LMPH1A [Accessed 28 June 2018], OMIM: Lymphedema, Hereditary, II; LMPH2 [Accessed 28 June 2018], OMIM: Yellow Nail Syndrome [Accessed 28 June 2018], OMIM: Lymphedema-Distichiasis Syndrome [Accessed 28 June 2018])
- Infectious: due to schistosomiasis in endemic areas; occasionally due to minor infection such as furuncle
- Obstructive: associated with malignancy or nodal dissection (axilla or groin most common)
- Traumatic: may be as minor as sprained ankle
- Idiopathic: called lymphedema praecox (if before age 35 years) or tarda
- All causes are associated with lymphangitis, cellulitis and recurrent infections
- Postmastectomy lymphedema may lead to angiosarcoma
Treatment
- Elevation of extremity, compression and massage; if necessary, excise thickened skin and replace with skin grafts
Microscopic (histologic) description
- Markedly dilated dermal lymphatics, including in lymph nodes
- Fibrous tissue deposition in overlying skin, subcutaneous tissue and fascia
Microscopic (histologic) images
Images hosted on other servers:
Additional references
Mantle cell / marginal zone hyperplasia
Definition / general
- Gene rearrangement studies and followup recommended to rule out occult lymphoma in cases with clear cells (Am J Clin Pathol 2001;116:550)
- Marginal zone hyperplasia is rare (except in mesenteric nodes) but does occur in reactive nodes (APMIS 2002;110:325)
Microscopic (histologic) description
- Monomorphic proliferation of small lymphocytes with clear cytoplasm and round nuclei
- No pericapsular infiltration, sinuses are identifiable, scattered reactive follicles
Microscopic (histologic) images
Contributed by Mark R. Wick, M.D.
Positive stains
- BCL2 (by marginal zone B cells) (Am J Surg Pathol 2003;27:888)
Negative stains
- No light chain restriction
Molecular / cytogenetics description
- Usually negative
Monocytoid B cell hyperplasia
Definition / general
- Benign disorders are toxoplasmosis, cat scratch disease, EBV, HIV, autoimmune disorders, zoonotic Brugia (Am J Surg Pathol 2005;29:595, Hum Pathol 1985;16:979, Am J Clin Pathol 1996;105:384)
- Also associated with mantle cell / marginal zone hyperplasia
Microscopic (histologic) description
- Sinuses distended by small lymphoid cells with clear cytoplasm and central, round / oval nuclei
- Variable neutrophils
Differential diagnosis
Additional references
Plasmacytosis
Definition / general
- Common in paracolic lymph nodes draining tumor (Virchows Arch A Pathol Anat Histopathol 1987;411:239)
- Associated with idiopathic plasmacytic lymphadenopathy, which resembles Castleman disease (Int J Surg Pathol 2004;12:25)
Case reports
- 72 year old woman with Sjögren syndrome and plasmacytosis resembling myeloma (J Korean Med Sci 2005;20:506)
Microscopic (histologic) description
- Well preserved nodal architecture with plasma cells and plasma cell precursors in medullary cords
- Sinuses are patent
Negative stains
- No light chain restriction
Molecular / cytogenetics description
- Not clonal
Differential diagnosis
- Plasmacytic SLL / CLL:
- Diffuse, not just involvement of medullary cords
Polykaryocytes
Definition / general
- Warthin-Finkeldey polykaryocytes are associated with various benign and malignant lymphoid conditions
- Initially identified in tonsils of patients with measles
- Also present in HIV patients
Case reports
- 65 year old woman with systemic lupus erythematosus (Hum Pathol 1988;19:1358)
Microscopic (histologic) description
- Multinucleated giant cells from 25 - 150 microns, with minimal cytoplasm and up to 60 nuclei
Microscopic (histologic) images
Images hosted on other servers:
Positive stains
Additional references
Sinus histiocytosis
Definition / general
- Also called sinus hyperplasia
- Nonspecific finding associated with various etiologies (benign or malignant), including postprosthesis
- May represent pregranulomatous phase of sarcoidosis (Am J Surg Pathol Acta Histochem 2006;107:473)
- Rarely occurs in pelvic nodes of prostate cancer and axillary nodes of breast cancer patients (Cancer 1997;80:277)
Case reports
- 16 year old girl with parvovirus (J Clin Pathol 2005;58:872)
- 68 year old woman with postarthroplasty histiocytic lymphadenopathy (Arch Gynecol Obstet 2004;269:217, J Urol 1997;158:128)
- 70 year old diabetic patient with signet ring cell sinus histiocytosis resembling carcinoma (Am J Clin Pathol 1989;92:509, Int J Clin Oncol 2003;8:184)
Microscopic (histologic) description
- Dilated and prominent sinuses, often containing increased macrophages or sinus lining cells
- May resemble signet ring cell carcinoma cells but lack atypia and are mucin negative
Microscopic (histologic) images
Images hosted on other servers:
Cytology description
- Polygonal histiocytes with rounded nuclei (Acta Cytol 1998;42:1347)
Board review style question #1
Board review style answer #1
A. The crystals in CSH in tissues get phagocytosed by histiocytes where they form collections. When these cells accumulate, they form a mass lesion.
Comment Here
Reference: Other nonspecific findings
Comment Here
Reference: Other nonspecific findings