NEET MDS Lessons
General Pathology
Hyperpituitarism
Causes
A. Pituitary; usually anterior lobe
1. Adenoma (the most common cause)
2. Hyperplasia
3. Carcinoma
B. Extra-pituitary causes
1. Hormone producing extra-pituitary tumors (ectopic hormone production)
2. Certain hypothalamic disorders
Pituitary adenomas are classified according to the hormone(s) produced by the neoplastic cells; these are detected by immunohistochemically-stained tissue sections. Pituitary adenomas can be functional (associated with hormone excess with their related clinical manifestations) or silent.
Pathogenesis
Guanine nucleotide-binding protein (G-protein) mutations are the best characterized molecular abnormalities. Such mutations eventuate in a persistent increase in intracellular cAMP, which is a potent mitogenic stimulus promoting cellular proliferation and hormone synthesis and secretion. In the setting of MEN-1 syndrome there are mutations in the MEN-1 (menin) gene.
Gross features
• Adenomas are usually soft & well-circumscribed
• Larger lesions extend superiorly through the sellar diaphragm compressing the optic chiasm and adjacent structures .
• Invasive adenomas refer to nonencapsulated tumors that infiltrate adjacent bone, dura, and even brain.
Microscopic features.
• Adenomas are composed of monomorphic, polygonal cells displayed in sheets, cords, or papillae. Their nuclei may be uniform or pleomorphic but the mitotic activity is scanty. The cytoplasm of the constituent cells may be acidophilic, basophilic, or chromophobic.
• The connective tissue is scanty that is why many lesions are soft & even gelatinous in consistency.
Prolactinomas are the most common type of hyperfunctioning pituitary adenoma.
Hyperprolactinemia causes amenorrhea, galactorrhea, loss of libido, and infertility.
Growth Hormone-Producing Adenomas (somatotroph cell adenomas) are the second most common type of functional pituitary adenoma. Because the clinical manifestations of excessive growth hormone may be subtle, the tumor may be quite large by the time they come to clinical attention. If such tumors occur before closure of epiphyses (prepubertal children), excessive levels of growth hormone result in gigantism. If elevated levels persist, or present after closure of the epiphyses, individuals develop acromegaly.
Corticotroph Cell Adenomas are mostly small (microadenomas) at the time of diagnosis. They may be clinically silent or cause hypercortisolism referred to as Cushing disease
Other Anterior Pituitary Neoplasms
• Gonadotroph adenomas (luteinizing hormone [LH]-producing and follicle-stimulating hormone [FSH]producing)
• Thyrotroph (thyroid-stimulating hormone [TSH]-producing) adenomas
• Nonfunctioning pituitary adenomas (hormone-negative (null cell) adenomas) Nonfunctioning adenomas constitute approximately 25% of all pituitary tumors; they typically present through their mass effects.
Multiple Endocrine Neoplasia Syndromes (MEN)
The MEN syndromes are a group of inherited diseases resulting in proliferative lesions (hyperplasias, adenomas, and carcinomas) of multiple endocrine organs. Even in one organ, the tumors are often multifocal. These tumors are usually more aggressive and recur in a higher proportion of cases than similar but sporadic endocrine tumors.
Multiple Endocrine Neoplasia Type 1 (MEN1) is inherited in an autosomal dominant pattern. The gene (MEN1) is a tumor suppressor gene; thus, inactivation of both alleles of the gene is believed to be the basis of tumorigenesis. Organs commonly involved include the parathyroid, pancreas, and pituitary (the 3 Ps). Parathyroid hyperplasia is the most consistent feature of MEN-1 but endocrine tumors of the pancreas are the leading cause of death because such tumors are usually aggressive and present with metastatic disease.
Zollinger-Ellison syndrome, associated with gastrinomas, and hypoglycemia, related to insulinomas, are common endocrine manifestations. Prolactin-secreting macroadenoma is the most frequent pituitary tumor in MEN-1 patients.
Multiple Endocrine Neoplasia Type 2 (MEN2)
MEN type 2 is actually two distinct groups of disorders that are unified by the occurrence of activating mutations of the RET protooncogene. Both are inherited in an autosomal dominant pattern.
MEN 2A
Organs commonly involved include:
Medullary carcinoma of the thyroid develops in virtually all cases, and the tumors usually occur in the first 2 decades of life. The tumors are commonly multifocal, and foci of C-cell hyperplasia can be found in the adjacent thyroid. Adrenal pheochromocytomas develop in 50% of patients; fortunately, no more than 10% are malignant. Parathyroid gland hyperplasia with primary hyperparathyroidism occurs in a third of patients.
Multiple Endocrine Neoplasia, Type 2B
Organs commonly involved include the thyroid and adrenal medulla. The spectrum of thyroid and adrenal medullary disease is similar to that in MEN-2A. However, unlike MEN-2A, patients with MEN-2B:
1. Do not develop primary hyperparathyroidism
2. Develop extraendocrine manifestations: ganglioneuromas of mucosal sites (gastrointestinal tract, lips, tongue) and marfanoid habitus
Parkinson’s disease
a. Characterized by the degeneration of neurons in the basal ganglia, specifically the substantia nigra and striatum.
b. Histologic findings in affected neurons include Lewy bodies.
c. Clinically, the disease affects involuntary and voluntary movements. Tremors are common. Symptoms include pin-rolling tremors, slowness of movements, muscular rigidity, and shuffling gait.
Neutrophilia
Causes
-Pyogenic infections.
-Haemorrhage and trauma.
-Malignancies.
-Infarction.
-Myelo proliferative disorders.
Herpes zoster, or shingles
- represents reactivation of a latent varicella-zoster infection.
- virus lies dormant in sensory dorsal root ganglia and when activated involves the distribution (dermatome) of the sensory nerve with a painful vesicular eruption.
- trigeminal verve distribution → Ramsay Hunt syndrome
- may indicate the presence of advanced neoplastic disease or be a complication of chemotherapy.