Sandbox:Preeti

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[2]

			Pathophysiology	Symptoms	Laboratory Findings
					Immunochemistry	Blood work	Biospy/CT/CXR
Infections	Bacterial	Syphilis	Syphilis is caused by a spirochete, Treponema pallidum. It has an average incubation period of 3 - 12 weeks. Spirochete penetrates intact mucous membrane or microscopic dermal abrasions and rapidly enters systemic circulation with the central nervous system being invaded during the early phase of infection. The histopathological hallmark findings are endarteritis and plasma cell-rich infiltrates reflecting a delayed-type of hypersensitivity reaction to the spirochete.	Primary syphilis Mononuclear leukocytic infiltration, macrophages, and lymphocytes Swelling and proliferation of small blood vessels Secondary syphilis Swelling and dilatation of blood vessels in the dermis Epidermal hyperplasia and neutrophilic infiltration Inflammatory cell infiltrate, predominantly plasma cell Tertiary syphilis Small vessel inflammation (endarteritis obliterans) Granulomatous lesions (gumma) containing central necrosis, inflammatory cells, such as lymphocytes, macrophages, plasma cells and fibroblasts.	A presumptive diagnosis of syphilis is possible with the use of two types of serologic tests. Nontreponemal tests (e.g., venereal disease research laboratory (VDRL) and rapid plasma reagent test) and Treponemal tests (e.g., fluorescent treponemal antibody absorbed (FTA-ABS) tests, the T. pallidum passive particle agglutination (TP-PA) assay, various enzyme immunoassays, and chemiluminescence immunoassays).		Darkfield examinations and tests to detect T. pallidum.
		Brucellosis	humans could be infected by eating undercook meat or raw dairy products, inhalation of the bacteria and direct contact of bacteria with skin wounds or mucous membranes. Following transmission, white blood cells phagocyte the pathogen and transports it via hematologic or lymphatic route to different organs specially to those of the reticuloendothelial system.	Fever Rash Abdominal pain weightloss Painful lymphadenopathy hepatosplenomegaly arthritis	Relative lymphocytosis positive titer of anti-brucella antibodies on serological testing There are two types of serological tests, based on: Antibody production against lipopolysaccharide Antibody production against other bacterial antigens		Brucella is most commonly isolated from blood cultures (blood cultures are positive between the 7th and 21st day)
	Viral	infectious mononucleosis	Epstein-Barr virus, frequently referred to as EBV, the virus infects B cells located in the oropharyngeal epithelium and subsequently spreads to involve the lymph nodes, liver and spleen. incubation period ranges from 4 to 6 weeks.	Characteristic triad of fever, pharyngitis, and lymphadenopathy lasting for 1 to 4 weeks. Common symptoms include low-grade fever without chills, sore throat, white patches on tonsils and back of the throat, muscle weakness and sometime extreme fatigue, tender lymphadenopathy, petechial hemorrhage and skin rash.	presence of atypical lymphocytes (often recorded by automated blood analyser machines as an increase in the monocycte count) is characteristic of EBV infection.	Peripheral Blood Smear hallmark of the disease is the presence of atypical lymphocytes (a type of mononuclear cell) . Atypical lymphocytosis is present in approximately 75% of patients Greater than 10% atypical lymphocytes is diagnostic of mononucleosis.
		cytomegalovirus	Presents with encephalitis, retinitis, progressive myelitis or polyradiculitis. In disseminated disease, it involves both liver and renal organs.	Common symptoms include sore throat, swollen lymph nodes, fever, headache, fatigue, weakness, muscle pain and loss of appetite. Abdominal examination reveals splenomegaly. Maculopapular rash may be present.	Positive monospot test. Elevated liver enzymes PCR of CSF with detectable virus is diagnostic.		CT/MRI/biopsy: location of lesions are usually near the brain stem or periventricular areas. Brain biopsy with + staining for CMV or evidence of owl's eyes is also diagnostic.
		human immunodeficiency virus	Acute HIV infection may be asymptomatic or may cause a mononucleosis-like syndrome	fever, fatigue, sore throat, myalgia, and lymphadenopathy
		cat scratch fever	The causative organism was first thought to be Afipia felis, but this was disproved by immunological studies demonstrating that cat scratch fever patients developed antibodies to two other organisms, Bartonella henselae (B. henselae) and Bartonella clarridgeiae, which are rod-shaped Gram-negative bacteria.	Symptoms of Cat scratch fever are: Painful lymphadenopathy Fever Chills Back pain Headache Sore throat Abdominal pain Vision problems Malaise Alteration of mental status Convulsions	Polymerase chain reaction (PCR) is the most sensitive test and is able to differentiate between different Bartonella species. Serological testing (indirect immunofluorescence or enzymatic immunoassay with titration of IgG or IgM antibodies) - to detect serum antibody to B henselae.	Complete blood count and differential count - lymphocytosis is seen in the acute phase. Erythrocyte sedimentation rate - elevated.
	Mycobacterial	tuberculosis	Mostly in endemic areas	Symptoms include productive cough,night sweats, fever and weight loss, hemoptysis	Sputum smear positive for acid-fast bacilliand nucleic acid amplification tests (NAAT) is used on sputum or any sterile fluid for rapid diagnosis and is positive for mycobacteria.	Mild normocytic anemia, hyponatremia, and hypercalcemia	CXR and CT demonstrates cavities in the upper lobe of the lung
	Parasitic	toxoplasmosis	A parasitic disease caused by ingestion of cat feces, affect all organs and particularly dangerous in pregnant woman. Toxoplasma infections may also present with a mononucleosis-like syndrome seen in patients with acute HIV syndrome.
Autoimmune	Systemic lupus erythematosus			skin rash, arthritis, positive autoimmune serology, weight loss, feversand chronic pain,		ESR and CRPelevated, positive ANA
	Sjögren's syndrome			skin rash, arthritis, positive autoimmune serology, weight loss, feversand chronic pain,
	Hydantoin derivatives
	Sarcoidosis		More common in African-American females Associated with restrictive lung disease Erythema nodosum Lupus pernio (skin lesions on face resembling lupus) Bell palsy Epithelioid granulomas containing microscopic Schaumann and asteroid bodies	Often asymptomatic except for enlarged lymph nodes			On CXR bilateral adenopathy and coarse reticular opacities are seen. CT of the chest demonstrates extensive hilar and mediastinal adenopathy Additional findings on CT include fibrosis (honeycomb, linear, or associated with bronchial distortion), pleural thickening, and ground-glass opacities. Biopsy of lung shows non-caseatinggranuloma
Neoplasms	Hodgkin's disease		Reed-Sternberg cell B-cell origin CD30 (Ki-1) and CD15 (Leu-M1) antigens	Painless localized peripheral lymphadenopathy B symptoms	Lactate dehydrogenase (LDH) may be increased. ESR elevated Serum creatinine elevated in nephrotic syndrome. Alkaline phosphatase (ALP) increased Hypercalcemia, hypernatremia, and hypoglycemia.		Fine-needle aspiration Mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells
	Chronic lymphocytic leukemia		Clonal B cells arrested in the B-cell differentiation pathway,. Genetic mutations that promote both malignantleukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion.	Fever Recurrent bleeding Weight loss Muscle wasting Generalized weakness Anorexia Night sweats Abdominal pain Recurrent infections	Monoclonality of kappa and lambda producing B cells Presence of smudge cells Express CD19, CD20, CD23, and CD5 on the cell surface	CBC Absolute lymphocytosis (>5000 cells/μl) Decreased hemoglobin concentration Decreased platelets count
	Small cell carcinoma of the lung		aggressive form of lung cancer and has the highest association with smoking. starts in the bronchi and expands through the bronchial mucosa and metastasizes rapidly. A mutation in the p53 gene is reported in 75%-100% of the cases.	relatively rapid onset of symptoms and is associated with the occurrence of paraneoplastic syndromes such as the syndrome of inappropriate antidiuresis (SIADH), hypercalcemia and many more. Cough (most common symptom) Wheezing Dyspnea Hemoptysis Chest pain	Nearly all SCLC are immunoreactive for keratin, thyroid transcription factor 1, epithelial membrane antigen Neuroendocrine and neural differentiation result in the expression of molecules like dopa-decarboxylase, calcitonin neuron-specific enolase, chromogranin A, CD56 gastrin-releasing peptide insulin-like growth factor 1		The confirmation of the diagnosis of SCLC is by tumor biopsy. patients with confirmed diagnosis of SCLC should undergo a CT scan of the abdomen for staging purposes. CT scan of the abdomen helps identify metastasis to organs, such as the liver or the adrenal glands.
	Malignant histiocytosis
	Melanoma		melanoma is the result of multiple genetic mutations. The progression to melanoma usually involves the serine-threonine kinases of the MAPK/ERK pathway (mitogen-activated protein kinase) following mutation of either the N-RAS or BRAF oncogene changes include the overexpression of N-cadherin, αVβ3 integrin, MMP-2, MSH, cAMP, and survivin, and the loss of E-cadherin and TRMP1 proteins	Symptoms of melanoma include the following: Rapid growth of an existing nevus Bleeding nevus Cutaneous nodules Hyper/hypopigmented skin lesion Lymphatic masses Melanonychia (brown/blue nail discoloration) Non-healing skin ulcer Painful skin lesion Pruritus Bone pain			An excisional biopsy (either elliptical, punch, or saucerization) of the thickest portion of the lesion with 1-3 mm margins is diagnostic.
	Germ cell neoplasms
Other conditions	Reactive lymphoid hyperplasia
	Lymphomatoid granulomatosis			Lymphamatoid granulomatosis manifests in a variety of clinical forms. Cough Dyspnea Chest tightness Malaise Weight loss Fatigue Fever Headaches Seizures Hemiparesis Ataxia Erythematous rash Macules Papules Plaques Subcutaneous nodules Larger ulcerated nodules		CBC Leukopenia Lymphopenia Low CD4 count Leukocytosis is rare Elevated Hematocrit	The following x-ray findings are suggestive of assisting in diagnosing Lymphmotoid granulomatosis: Bilateral nodules or masses in the lower and peripheral lung Pulmonary infiltrates Pleural effusion in some cases Cavitation of nodules Chest CT scan may be helpful in the diagnosis of Lymphomatoid granulomatosis. Findings on CT scan suggestive of/diagnostic of Lymphomatoid granulomatosis include: Nodules Cavitations Masses Halo sign is seen due to the angioinvasive nature of the disease
	Dermatopathic lymphadenopathy
	Angioimmunoblastic lymphadenopathy		Clonal T-cell receptor and immunoglobulin gene rearrangements Epstein–Barr virus (EBV) has been found in both reactive B-cells and the neoplastic T-cells. Trisomy 3, trisomy 5, and +X are the most frequent chromosomal abnormalities found in cases.. Characteristic findings on gross pathology, aborization and proliferation of high endothelial venules On microscopic histopathological analysis, CD4+ T-cells, CD8+ T-cells, and polyclonal plasma cells.	Symptoms include: Fever Weight loss Skin rash Night sweats Edema Chest pain Abdominal pain Bone pain Painless swelling in the neck, axilla, groin, thorax, and abdomen Fatigue Pale skin color Dark urine Chronic pain and swelling of the joints	Immunophenotyping Positivity for CD2, CD3, CD4, CD5, CD10, CD20, and focal positivity for CXCL13 Negative for ALK1 and CD30 Fluorescence in situ hybridization (FISH)	Complete blood count (CBC) Anemia Eosinophilia	Lymph node or extranodal tissue biopsy is diagnostic of angioimmunoblastic T-cell lymphoma. CT scan suggestive of angioimmunoblastic T-cell lymphoma include: Mediastinal lymphadenopathy Inguinal lymphadenopathy Aortal lymphadenopathy Bilaterally enlarged kidneys
	Giant lymph node hyperplasia (Castleman disease)		Castleman's disease is likely due to hypersecretion of the cytokine IL-6. In KSHV positive tumors, this is most likely due to expression of the a virus-encoded cytokine, vIL-6, while KSHV negative tumors appear to be the result of over secretion of human IL-6.	The most common 'B symptoms' of MCD are High fevers Anemia Weight loss Loss of appetite Other symptoms include: Cough Chest discomfort Fatigue Weakness		Complete blood count and differential count - low white blood cell counts, which may to be due to the overproduction of interleukin 6. Erythrocyte sedimentation rate - elevated in 80% cases.