Lymph Node Enlargement (Lymphadenopathy): Or something else? Differential Diagnosis

Respiratory System (J00-J99)

Blood, blood-forming organs – immune system (D50-D90).

  • Autoimmunologic lymphoproliferative syndrome.
  • Hemophagocytic lymphohistiocytosis – rare disorder characterized by high fever, spleen, liver and lymph node enlargement.
  • Immunodeficiencies, unspecified
  • Rosai-Dorfman syndrome (synonym: sinus histiocytosis with massive lymphadenopathy; English : Rosai-Dorfman disease) – rare disorder belonging to the group of histiocytoses (group of disorders due to increased proliferation of tissue-derived macrophages (histiocytes)); marked, bilateral enlargement of cervical lymph nodes (neck lymph nodes); sporadic occurrence.
  • Sarcoidosis (synonyms: Boeck’s disease; Schaumann-Besnier’s disease) – systemic disease of connective tissue with granuloma formation (skin, lungs and lymph nodes).

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Amyloidosis – extracellular (“outside the cell”) deposits of amyloids (degradation-resistant proteins) that can lead to cardiomyopathy (heart muscle disease), neuropathy (peripheral nervous system disease), and hepatomegaly (liver enlargement), among other conditions.
  • Hypertriglyceridemia (elevation of triglycerides in the blood).
  • Hyperthyroidism (hyperthyroidism)
  • Lipoprotein deficiency, unspecified
  • Fabry disease (synonyms: Fabry disease or Fabry-Anderson disease) – X-linked lysosomal storage disease due to a defect in the gene encoding the enzyme alpha-galactosidase A, resulting in progressive accumulation of the sphingolipid globotriaosylceramide in cells; mean age of manifestation: 3-10 years; early symptoms: Intermittent burning pain, decreased or absent sweat production, and gastrointestinal problems; if left untreated, progressive nephropathy (kidney disease) with proteinuria (increased excretion of protein in urine) and progressive renal failure (kidney weakness) and hypertrophic cardiomyopathy (HCM; disease of the heart muscle characterized by thickening of the heart muscle walls).
  • Gaucher disease – genetic disease with autosomal recessive inheritance; lipid storage disease due to the defect of the enzyme beta-glucocerebrosidase, which leads to the storage of cerebrosides mainly in the spleen and marrow-containing bones.
  • Niemann-Pick disease (synonyms: Niemann-Pick disease, Niemann-Pick syndrome or sphingomyelin lipidosis) – genetic disease with autosomal recessive inheritance; belongs to the group of sphingolipidoses, which in turn are classified as lysosomal storage diseases; main symptoms of Niemann-Pick disease type A are hepatosplenomegaly (liver and spleen enlargement) and psychomotor decline; in type B, no cerebral symptoms are observed.
  • Tangier’s disease (synonym: Tangier disease) – rare genetic disease with autosomal recessive inheritance; lipid metabolism disorder; here, the release of cholesterol from the cell is disturbed; the disease is associated with decreased formation of high-density lipoproteins (HDL) and increased cholesterol storage in cells of the reticulohistiocytic system; leading symptoms are yellow-orange spots on enlarged tonsils (tonsils); hepatosplenomegaly (liver and spleen enlargement).
  • Storage diseases, unspecified

Skin and subcutaneous (L00-L99)

  • Lymphomatoid granulomatosis – generalized occurrence of granulomas (benign tumors), if any.
  • Serum sickness – immune complex disease that occurs after usually a single supply of protein foreign to the species.

Cardiovascular system (I00-I99)

  • Angioimmunoblastic lymphadenopathy (lymph node disease).
  • Heart failure (cardiac insufficiency)
  • Kikuchi-Fujimoto disease – benign, self-limited disease with symptoms of circumscribed, tender swelling of the lymph nodes of the neck and usually also mild fever and night sweats; less common symptoms include weight loss, nausea, vomiting, and sore throat; found primarily in Southeast Asia and Japan (see orpha.net below).
  • Nonspecific lymphadenitis – inflammatory swelling of the lymph nodes.

Infectious and parasitic diseases (A00-B99).

  • Bacterial infections such as:
    • Bartonella henselae (cat scratch disease).
    • Brucellosis
    • Chlamydia trachomati, serotype L1-L3 /Lymphogranuloma venereum
    • Klebsiella granulomatis (formerly Callymmatobacterium granulomatis) /Granuloma inguinale (Granuloma venereum).
    • Mycobacterium tuberculosis complex /tuberculosis (v. a. lymph node tuberculosis).
    • Non-tuberculous mycobacterioses (NTM/MOTT).
    • Spirochetes
    • Staphylococci (Staphylococcus aureus)
    • Streptococci (β-hemolytic group A streptococci).
    • Treponema pallidum / syphilis
    • Tropheryma whippelii
    • Tularaemia
    • Yersinia (lymphadenitis mesenterialis)
  • Infections with parasites such as:
    • Filariae (tropical worms)
    • Toxoplasmosis
  • Infections with mycoses (fungi) such as:
    • Blastomycosis
    • Histoplasmosis
  • Viral infections such as:
    • Adenoviruses
    • Coxsackie
    • Enteroviruses
    • Epstein-Barr virus (EBV) / Pfeiffer’s glandular fever (infectious mononucleosis).
    • Human immunodeficiency virus (HIV) / AIDS
    • Influenza
    • Measles virus
    • Rhinovirus
    • Rubella virus
    • Viral hepatitides
    • Etc.
  • Tropical infectious diseases: Filariasis, leprosy, trypanosomiasis, tularemia.

Liver, gallbladder and bile ducts – Pancreas (pancreas) (K70-K77; K80-K87).

  • Primary biliary cholangitis (PBC, synonyms: nonpurulent destructive cholangitis; formerly primary biliary cirrhosis) – relatively rare autoimmune disease of the liver (affects women in about 90% of cases); begins primarily biliary, i.e., at the intrahepatic and extrahepatic (“inside and outside the liver”) bile ducts, which are destroyed by inflammation (= chronic nonpurulent destructive cholangitis). In the longer course, the inflammation spreads to the entire liver tissue and eventually leads to scarring and even cirrhosis; detection of antimitochondrial antibodies (AMA); PBC is frequently associated with autoimmune diseases (autoimmune thyroiditis, polymyositis, systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis); associated with ulcerative colitis (inflammatory bowel disease) in 80% of cases; long-term risk of cholangiocellular carcinoma (bile duct carcinoma, bile duct cancer) is 7-15%.

Mouth, esophagus (food pipe), stomach, and intestine (K00-K67; K90-K93).

Musculoskeletal system and connective tissue (M00-M99).

  • Dermatomyositis – disease of the collagenoses, leading to pain on movement and muscle involvement.
  • Juvenile idiopathic arthritis – joint inflammation that occurs before the age of 16.
  • Kawasaki syndrome – acute, febrile, systemic disease characterized by necrotizing vasculitis (vascular inflammation) of small and medium-sized arteries.
  • Rheumatoid arthritis (chronic polyarthritis).
  • Sharp syndrome – connective tissue disease that shows the symptoms of various autoimmune diseases such as systemic lupus erythematosus (SLE), scleroderma, chronic polyarthritis, etc.
  • Sjögren’s syndrome (group of sicca syndromes) – autoimmune disease from the group of collagenoses, which leads to a chronic inflammatory disease of the exocrine glands, most commonly the salivary and lacrimal glands; typical sequelae or complications of sicca syndrome are:
    • Keratoconjunctivitis sicca (dry eye syndrome) due to lack of wetting of the cornea and conjunctiva with tear fluid.
    • Increased susceptibility to caries due to xerostomia (dry mouth) due to reduced salivary secretion.
    • Rhinitis sicca (dry nasal mucous membranes), hoarseness and chronic cough irritation and impaired sexual function due to disruption of mucous gland production of the respiratory tract and genital organs.
  • Still’s syndrome (synonym: Still’s disease): systemic form of juvenile rheumatoid arthritis occurring in children with hepatosplenomegaly (enlargement of the liver and spleen), fever (≥ 39 °C, over 14 days), generalized lymphadenopathy (enlargement of the lymph nodes), carditis (inflammation of the heart), transient exanthema (skin rash), anemia (anemia). The prognosis of this disease is unfavorable.
  • Systemic lupus erythematosus (SLE) – autoimmune disease with formation of autoantibodies mainly against antigens of the cell nuclei (so-called antinuclear antibodies = ANA), possibly also against blood cells and other body tissues (particularly characteristic of SLE is the so-called butterfly erythema).

Neoplasms – tumor diseases (C00-D48).

  • Histiocytosis/Langerhans-cell histiocytosis (abbreviation: LCH; formerly: histiocytosis X; Engl. histiocytosis X, langerhans-cell histiocytosis) – systemic disease with proliferation of Langerhans cells in various tissues (skeleton 80% of cases; skin 35%, pituitary gland (pituitary gland) 25%, lung and liver 15-20%); in rare cases neurodegenerative signs may also occur; in 5-50 % of cases, diabetes insipidus (hormone deficiency-related disturbance in hydrogen metabolism, leading to extremely high urine excretion) occurs when the pituitary gland is affected; the disease occurs disseminated (“distributed over the whole body or certain regions of the body”) frequently in children between 1-15 years of age, less frequently in adults, here predominantly with an isolated pulmonary affection (lung affection); prevalence (disease frequency) approx. 1-2 per 100,000 inhabitants
  • Leukemia (blood cancer)
  • Lymph node metastases in any type of malignant tumor (cancer).
  • Lymphoma – malignant disease originating in the lymphatic system: e.g. Hodgkin’s lymphoma, non-Hodgkin’s lymphoma.
  • Lymphoproliferative disorders such as Castleman’s disease (hypertrophy of the lymph nodes with angiofollicular lymph hyperplasia) – benign lymph node enlargement.
  • Malignant histiocytosis
  • Metastases (daughter tumors) of a wide variety of malignant (malignant) tumors.
  • Plasmocytoma (multiple myeloma) – belongs to the non-Hodgkin’s lymphoma of B lymphocytes.

Injuries, poisonings, and other consequences of external causes (S00-T98).

Further

  • Periodic fever syndromes
  • Silicone-associated
  • Vascular sinus transformation – term from pathology denoting a transformation of the lymph node structure.

Medication

Prognostic factors

Lymph node enlargement and dignity* .

Lymph node enlargement Benign (benign) Malignant (malignant)
<30 years of age 80 % 20 %
> 50. year of life 40 % 60 %

* Biological behavior of tumors; i.e., whether they are benign (benign) or malignant (malignant).

Risk factors for malignancy (malignancy).

Anamnesis (medical history) Male gender
Age > 40 years
Duration of lymphadenopathy (lymph node enlargement) > 4 weeks
Examination findings Generalized lymphadenopathy (≥ 2 involved lymph node regions), supraclavicular lymphadenopathy (lymph node enlargement above the clavicle/clavicle)
Failure of lymph node size to normalize after 8-12 weeks.
No pressure dolence (pressure pain) of the lymph nodes
Other symptoms B symptoms

  • Unexplained, persistent, or recurrent fever (>38 °C).
  • Severe night sweats (wet hair, soaked sleepwear).
  • Unintentional weight loss (>10% percent of body weight within 6 months).

Hepatomegaly (enlargement of the liver and spleen).