Huntington’s disease
a. Causes dementia.
b. Genetic transmission: autosomal dominant.
c. Characterized by the degeneration of striatal neurons, affecting cortical and basal ganglia function.
d. Clinically, the disease affects both movement and cognition and is ultimately fatal.

Systemic Candidiasis (Candidosis; Moniliasis)

Invasive infections caused by Candida sp, most often C. albicans, manifested by fungemia, endocarditis, meningitis, and/or focal lesions in liver, spleen, kidneys, bone, skin, and subcutaneous or other tissues.

Infections due to Candida sp account for about 80% of all major systemic fungal infections.

Symptoms and Signs

Esophagitis is most often manifested by dysphagia. Symptoms of respiratory tract infections are nonspecific, such as cough. Vaginal infections cause itching, burning, and discharge. Candidemia usually causes fever, but other symptoms are typically nonspecific. Sometimes, a syndrome develops resembling bacterial sepsis, with a fulminating course that may include shock, oliguria, renal shutdown, and disseminated intravascular coagulation.

Hematogenous endophthalmitis starts as white retinal plaques that can cause blindness as destructive inflammation progresses, extending to opacify the vitreous and causing potentially irreversible scarring. Most often, there are no symptoms in early stages of Candida endophthalmitis. If treatment is not begun before symptoms appear, significant or even total loss of vision is likely to occur in the affected eye. In neutropenic patients, eye involvement is more often manifested by retinal hemorrhages; papulonodular, erythematous, and vasculitic skin lesions may also develop.

Lymphomas

A. Hodgkin’s disease

1. Characterized by enlarged lymph nodes and the presence of Reed-Sternberg cells (multinucleated giant cells) in lymphoid tissues.

2. Disease spreads from lymph node to lymph node in a contiguous manner.

3. Enlarged cervical lymph nodes are most commonly the first lymphadenopathy observed.

4. The cause is unknown.

5. Occurs before age 30.

6. Prognosis of disease depends largely on the extent of lymph node spread and systemic involvement.

B. Non-Hodgkin’s lymphoma

1. Characterized by tumor formation in the lymph nodes.

2. Tumors do not spread in a contiguous manner.

3. Most often caused by the proliferation of abnormal B cells.

4. Occurs after age 40.

5. Example: Burkitt’s lymphoma

a. Commonly associated with an EpsteinBarr virus (EBV) infection and a genetic mutation resulting from the translocation of the C-myc gene from chromosome 8 to 14.

b. The African type occurs in African children and commonly affects the mandible or maxilla.

c. In the United States, it most commonly affects the abdomen.

d. Histologically, the tumor displays a  characteristic “starry-sky” appearance.

Miscellaneous Bone Tumors 

1. Ewing Sarcoma & Primitive Neuroectodermal Tumor (PNET) are primary malignant small round-cell tumors of bone and soft tissue. They are viewed as the same tumor because they share an identical chromosome translocation; they differ only in degree of differentiation. PNETs demonstrate neural differentiation whereas Ewing sarcomas are undifferentiated. After osteosarcomas, they are the second most common pediatric bone sarcomas. Most patients are 10 to 15 years old. The common chromosomal abnormality is a translocation that causes fusion of the EWS gene with a member of the ETS family of transcription factors. The resulting hybrid protein functions as an active transcription factor to stimulate cell proliferation. These translocations are of diagnostic importance since almost all patients with Ewing tumor have t(11;22).

Pathological features

• Ewing sarcoma and PNETs arise in the medullary cavity but eventually invade the cortex and periosteum to produce a soft tissue mass.
• The tumor is tan-white, frequently with foci of hemorrhage and necrosis.

Microscopic features

• There are sheets of uniform small, round cells that are slightly larger than lymphocytes with few mitoses and little intervening stroma.
• The cells have scant glycogen-rich cytoplasm.
• The presence of Homer-Wright rosettes (tumor cells circled about a central fibrillary space) indicates neural differentiation, and hence indicates by definition PNET. 

Ewing sarcoma and PNETs typically present as painful enlarging masses in the diaphyses of long tubular bones (especially the femur) and the pelvic flat bones. The tumor may be confused with osteomyelitis because of its association with systemic signs & symptoms of infection. X-rays show a destructive lytic tumor with infiltrative margins and extension into surrounding soft tissues. There is a characteristic periosteal reaction depositing bone in an onionskin fashion. 

2. Giant-Cell Tumor of Bone (GCT) is dominated by multinucleated osteoclast-type giant cells, hence the synonym osteoclastoma. GCT is benign but locally aggressive, usually arising in individuals in their 20s to 40s. Current opinion suggests that the giant cell component is likely a reactive macrophage population and the mononuclear cells are neoplastic. Tumors are large and red-brown with frequent cystic degeneration. They are composed of uniform oval mononuclear cells with frequent mitoses, with scattered osteoclast-type giant cells that may contain 30 or more nuclei.

The majority of GCTs arise in the epiphysis of long bones around the knee (distal femur and proximal tibia).
Radiographically, GCTs are large, purely lytic, and eccentric; the overlying cortex is frequently destroyed, producing a bulging soft tissue mass with a thin shell of reactive bone. Although GCTs are benign, roughly 50% recur after simple curettage; some malignant examples (5%) metastasize to the lungs 

TUBERCULOSIS

A chronic, recurrent infection, most commonly in the lungs

Etiology, Epidemiology, and Incidence

TB refers only to disease caused by Mycobacterium tuberculosis, M. bovis, or M. africanum. Other mycobacteria cause diseases similar to TB

Pathogenesis

The stages of TB are primary or initial infection, latent or dormant infection, and recrudescent or adult-type TB.

Primary TB may become active at any age, producing clinical TB in any organ, most often the apical area of the lung but also the kidney, long bones, vertebrae, lymph nodes, and other sites. Often, activation occurs within 1 to 2 yr of initial infection, but may be delayed years or decades and activate after onset of diabetes mellitus, during periods of stress, after treatment with corticosteroids or other immunosuppressants, in adolescence, or in later life (> 70 yr of age), but especially after HIV infection. The initial infection leaves nodular scars in the apices of one or both lungs, called Simon foci, which are the most common seeds for later active TB. The frequency of activation seems unaffected by calcified scars of primary infection (Ghon foci) or by residual calcified hilar lymph nodes. Subtotal gastrectomy and silicosis also predispose to development of active TB.

Pulmonary Tuberculosis

recrudescent disease occurs in nodular scars in the apex of one or both lungs (Simon foci) and may spread through the bronchi to other portions

Recrudescence may occur while a primary focus of TB is still healing but is more often delayed until some other disease facilitates reactivation of the infection.

In an immunocompetent person whose tuberculin test is positive (>= 10 mm), exposure to TB rarely results in a new infection, because T-lymphocyte immunity controls small, exogenous inocula promptly and completely.

Symptoms and Signs:

Cough is the most common symptom,

At first, it is minimally productive of yellow or green mucus, usually on rising in the morning, but becomes more productive as the disease progresses

Dyspnea may result from rupture of the lung or from a pleural effusion caused by a vigorous inflammatory reaction

Hilar lymphadenopathy is the most common finding in children. due to lymphatic drainage from a small lesion, usually located in the best ventilated portions of the lung (lower and middle lobes), where most of the inhaled organisms are carried.

swelling of the nodes is common

Untreated infection may progress to miliary TB or tuberculous meningitis and, if long neglected, rarely may lead to pulmonary cavitation.

TB in the elderly presents special problems. Long-dormant infection may reactivate, most commonly in the lung but sometimes in the brain or a kidney, long bone, vertebra, lymph node, or anywhere that bacilli were seeded during the primary infection earlier in life

TB may develop when infection in an old calcific lymph node reactivates and leaks caseous material into a lobar or segmental bronchus, causing a pneumonia that persists despite broad-spectrum antibiotic therapy.

With HIV infection, progression to clinical TB is much more common and rapid.

HIV also reduces both inflammatory reaction and cavitation of pulmonary lesions. As a result, a patient's chest x-ray may be normal, even though AFB are present in sufficient numbers to show on a sputum smear. Recrudescent TB is almost always indicated when such an infection develops while the CD4⁺ T-lymphocyte count is >= 200/µL. By contrast, the diagnosis is usually infection by M. avium-intracellulare if the CD4+ count is < 50. The latter is noninfectious for others.

Pleural TB develops when a small subpleural pulmonary lesion ruptures, extruding caseous material into the pleural space. The most common type, serous exudate, results from rupture of a pimple-sized lesion of primary TB and contains very few organisms.

Tuberculous empyema with or without bronchopleural fistula is caused by a more massive contamination of the pleural space resulting from rupture of a large tuberculous lesion. Such a rupture allows air to escape and collapse the lung. Either type requires prompt drainage of pus and initiation of multiple drug therapy

Extrapulmonary Tuberculosis

Remote tuberculous lesions can be considered as metastases from the primary site in the lung, comparable to metastases from a primary neoplasm. TB of the tonsils, lymph nodes, abdominal organs, bones, and joints were once commonly caused by ingestion of milk infected with M. bovis.

GENITOURINARY TUBERCULOSIS

The kidney is one of the most common sites for extrapulmonary (metastatic) TB. Often after decades of dormancy, a small cortical focus may enlarge and destroy a large part of the renal parenchyma.

Salpingo-oophoritis can be a complication of primary TB after onset of menarche, when the fallopian tubes become vascular.

TUBERCULOUS MENINGITIS

Spread of TB to the subarachnoid space may occur as part of generalized dissemination through the bloodstream or from a superficial tubercle in the brain

Symptoms are fever (temperature rising to 38.3° C [101° F]), unremitting headache, nausea, and drowsiness, which may progress to stupor and coma. Stiff neck (Brudzinski's sign) and straight leg raising are inconstant but are helpful signs, if present. Stages of tuberculous meningitis are (1) clear sensorium with abnormal CSF, (2) drowsiness or stupor with focal neurologic signs, and (3) coma. Likelihood that CNS defects will become permanent increases with the stage. Symptoms may progress suddenly if the lesion causes thrombosis of a major cerebral vessel.

Diagnosis is made by examining CSF. The most helpful CSF findings include a glucose level < 1/2 that in the serum and an elevated protein level along with a pleocytosis, largely of lymphocytes. Examination of CSF by PCR is most helpful, rapid, and highly specific.

MILIARY TUBERCULOSIS

When a tuberculous lesion leaks into a blood vessel, massive dissemination of organisms may occur, causing millions of 1- to 3-mm metastatic lesions. Such spread, named miliary because the lesions resemble millet seeds, is most common in children < 4 yr and in the elderly.

TUBERCULOUS LYMPHADENITIS

In primary infection with M. tuberculosis, the infection spreads from the infected site in the lung to the hilar nodes. If the inoculum is not too large, other nodes generally are not involved. However, if the infection is not controlled, other nodes in the superior mediastinum may become involved. If organisms reach the thoracic duct, general dissemination may occur. From the supraclavicular area, nodes in the anterior cervical chain may be inoculated, thus sowing the seeds for tuberculous lymphadenitis at a later time. Most infected nodes heal, but the organisms may lie dormant and viable for years or decades and can again multiply and produce active disease.

Cells Of  The Exudate

Granulocytes (Neutrophils, eosinophils, and basophils)

Monocytes (and tissue macrophages)

Lymphocytes

Neutrophils (polymorphs).

Characteristics

(1) Cell of acute inflammation.

(2) Actively motile.

(3) Phagocytic.

(4) Respond to chemotactic agents like.

Complement products.

Bacterial products.

Tissue breakdown

Lysosomal enzymes of other polymorphs

Functions

(1) Phagocytosis and intracellular digestion of bacteria.

(2) Exocytosis of lysosomal enzymes to digest dead tissue as the first step in the process of repair.

Eosinophils

Characteristics

(I) Cell of allergjc and immunologic inflammation.

(2) Motile and phagocytic but less so than a neutrophil.

(3) Response to chemotaxis similar to neutrophil. In addition, it is also responsive to antigens and antigen-antibody complexes.

(4) Steroids cause depletion of eosinophils.

Functions

(1) Contain most of the lysosomal enzymes that polymorphs have

(2) control of Histamine release and degradation in inflammation

Basophils (and mast cells)

Characteristics

(1) Contain coarse metachromatic granules.

(2) Contain, histamine and proteolytic enzymes

Functions

Histamine: release which causes some of the changes of inflammation and allergic

reactions. .

Monocytes .

Blood monocytes form a component of. the mononuclear phagocytic system (MPS), the other being tissue macrophages The tissue macrophages may be :

(a) Fixed phagocytic. cells:

• Kuffer cell of liver.
• Sinusoidal lining cells of spleen and lymph nodes.
• Pleural and peritoneal macrophages
• Alveolar macrophages.
• Microglial cells.

(b) Wandering macrophages or tissue histiocytes.

The tissue histiocytes are derived from blood monocytes.

Characteristics

.(1)Seen in inflammation of some duration, as they -outlive polymorphs.

(2) Actively phagocytic and motile.

(3) Fuse readily to from giant cells in certain situations.

Function

(1) Phagocytosis.

(2) Lysosomal enzyme secretion.

(3) Site of synthesis of some components of complement.

(4) Antigen handling and processing before presenting it to the Immune  competent cell.

(5) Secretion of lysosyme and interferon.

Giant cells can be

(A) Physiological

Syncytiotrophoblast, megakatyocytes, striated muscle, osteoclast.

(B) Pathological:

Foreign body: in the presence of particulate foreign matter like talc, suture material etc. and in certain infections_e g fungal.

Langhan's type: a variant of foreign body giant cell seen in tuberculosis.

Touton type in lipid rich situations like Xanthomas, lipid granulomas etc.

(iv) Aschoff cell in rheumatic carditis.

(v) Tumour gjant cells e.g. Reid-Sternberg cell in Hodgkin's Lymphoma, giant cells in any malignancy.

Lymphocytes and Plasma cells

These are the small mononuclear cell comprising the immune system

They are less motile than_macrophages and  neutrophils and are seen in chronic inflammation and immune based diseases.