NEET MDS Lessons
General Pathology
Fibrous and Fibro-Osseous Tumors
Fibrous tumors of bone are common and comprise several morphological variants.
1. Fibrous Cortical Defect and Nonossifying Fibroma
Fibrous cortical defects occur in 30% to 50% of all children older than 2 years of age; they are probably developmental rather than true neoplasms. The vast majority are smaller than 0.5 cm and arise in the metaphysis of the distal femur or proximal tibia; almost half are bilateral or multiple. They may enlarge in size (5-6 cm) to form nonossifying fibromas. Both lesions present as sharply demarcated radiolucencies surrounded by a thin zone of sclerosis. Microscopically are cellular and composed of benign fibroblasts and macrophages, including multinucleated forms. The fibroblasts classically exhibit a storiform pattern. Fibrous cortical defects are asymptomatic and are usually only detected as incidental radiographic lesions. Most undergo spontaneous differentiation into normal cortical bone. The few that enlarge into nonossifying fibromas can present with pathologic fracture; in such cases biopsy is necessary to rule out other tumors.
2. Fibrous Dysplasia
is a benign mass lesion in which all components of normal bone are present, but they fail to differentiate into mature structures. Fibrous dysplasia occurs as one of three clinical patterns:
A. Involvement of a single bone (monostotic)
B. nvolvement of multiple bones (polyostotic)
C. Polyostotic disease, associated with café au lait skin pigmentations and endocrine abnormalities, especially precocious puberty (Albright syndrome).
Monostotic fibrous dysplasia accounts for 70% of cases. It usually begins in early adolescence, and ceases with epiphyseal closure. It frequently involves ribs, femur, tibia & jawbones. Lesions are asymptomatic and usually discovered incidentally. However, fibrous dysplasia can cause marked enlargement and distortion of bone, so that if the face or skull is involved, disfigurement can occur.
Polyostotic fibrous dysplasia without endocrine dysfunction accounts for the majority of the remaining cases.
It tends to involve the shoulder and pelvic girdles, resulting in severe deformities and spontaneous fractures.
Albright syndrome accounts for 3% of all cases. The bone lesions are often unilateral, and the skin pigmentation is usually limited to the same side of the body. The cutaneous macules are classically large, dark to light brown (café au lait), and irregular.
Gross features
• The lesion is well-circumscribed, intramedullary; large masses expand and distort the bone.
On section it is tan-white and gritty.
Microscopic features
• There are curved trabeculae of woven bone (mimicking Chinese characters), without osteoblastic rimming
• The above are set within fibroblastic proliferation
Individuals with monostotic disease usually have minimal symptoms. By x-ray, lesions exhibit a characteristic ground-glass appearance with well-defined margins. Polyostotic involvement is frequently associated with progressive disease, and more severe skeletal complications (e.g., fractures, long bone deformities, and craniofacial distortion). Rarely, polyostotic disease can transform into osteosarcoma, especially following radiotherapy.
Metastatic Tumors
These are the most common malignant tumor of bone. Certain tumors exhibit a distinct skeletal prediliction. In adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung. In children, neuroblastoma, Wilms' tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the common sources of bony metastases. Most metastases involve the axial skeleton (vertebral column, pelvis, ribs, skull, sternum), proximal femur, and humerus. The radiologic appearance of metastases can be purely osteolytic, purely osteoblastic, or mixed osteolytic-osteoblastic (majority of cases). In lytic lesions (e.g., kidney& lung), the metastatic cells secrete substances such as prostaglandins, interleukins, etc. that stimulate osteoclastic bone resorption; the tumor cells themselves do not directly resorb bone. Similarly, metastases that elicit a blastic response (e.g., prostate adenocarcinoma) do so by stimulating osteoblastic bone formation.
Psoriasis is a chronic disorder characterized by scaly, erythematous plaques, which histologically are secondary to epidermal proliferation.
- genetic factors (HLA relationships), environmental (physical injury, infection, drugs, photosensitivity), abnormal cellular proliferation (deregulation of epidermal proliferation) and microcirculatory changes in the papillary dermis (diapedesis of neutrophils into the epidermis) are all interrelated.
- the plaques of psoriasis are characteristically well-demarcated pink or salmon colored lesions covered by a loosely-adherent silver-white scale which, when picked off, reveals pinpoint bleeding sites (Auspitz sign).
- the nail changes in psoriasis include pitting, dimpling, thickening and crumbling with a yellowish-brown discoloration of the nail plate.
- the characteristic histologic features of psoriasis include:
- hyperkeratosis
- absence of the granulosa cells (present in lichen planus).
- parakeratosis
- regular, club-shaped elongation of the rete pegs (irregular and saw toothed in lichen planus) with vessel proliferation in the papillary dermis (reason for the bleeding associated with Auspitz sign).
- characteristic subcorneal collection of neutrophils called a Munro's microabscess (diapedesis from vessels in papillary dermi).
- 7% develop HLA B27 positive psoriatic arthritis
Chickenpox (varicella)
- primarily a childhood disease (70%)
- incubation period 14-16 days; highly contagious; infectious 2 days before the vesicles until the last one dries.
- present with generalized, intensely pruritic skin lesions starting as macules vesicles pustules (MVP-most valuable player) usually traveling centrifugally to the face and out to the extremities; unlike smallpox vesicles, chickenpox vesicles appear in varying stages of development as successive crops of lesions appear; intranuclear inclusions similar to HSV.
- pneumonia develops in 1/3 of adults; MCC death in chickenpox.
- association with Reye's syndrome if child takes aspirin.
Infections caused by N. meningiditis
1. Bacteremia without sepsis. Organism spreads to blood but no major reaction.
2. Meningococcemia without meningitis. Fever, headache, petechia, hypotension, disseminated intravascular coagulation. The Waterhouse-Friderichsen Syndrome is a rapid, progressive meningococcemia with shock, organ failure, adrenal necrosis, and death.
3. Meningitis with meningococcemia. Sudden onset fever, chills, headache, confusion, nuchal rigidity. This occurs rapidly.
4. Meningoencephalitis. Patients are deeply comatose.
Diagnosis made by examining CSF.
Leukaemias
Uncontrolled proliferation of leukocyte precursors (may be with associated red cell and platelet series proliferation).
Factors which may playa causal role are.
- Viral
- Radiation.
- Genetic.
Classification
1. Acule leukaemia:
a. Lymphocytic (lymphoblastic).
b. Myelocytic and promyelocytic (myeloblastic).
c. Monocytic.
d. Myelomonocytic.
e. Undifferentiated (Stem cell).
2. Chronic leukaemia:
a. Lymphocytic
b. Myelocytic
3. Miscellaneous:
a. Erythroleukaemia (De Guglielmo's disease).
b. Eosinophilic leukaemia.
c. Megakaryocytic leukaemia.
Bacterial meningitis (pyogenic, suppurative infections)
1. Common causes include:
a. Escherichia coli in newborns.
b. Haemophilus influenzae in infants and children.
c. Neisseria meningitides in young adults.
d. Streptococcus pneumoniae and Listeria monocytogenes in older adults.
Clinical findings include severe headache, irritability, fever, and a stiff neck.
a. A spinal tap shows CSF fluid that is cloudy or purulent and is under increased pressure. There is also an increase in protein and a decrease in glucose levels.
3. Can be fatal if left untreated.