Pagets Disease

Paget disease of bone For treatment of Paget disease of bone where alkaline phosphatase is at least 2 times the upper limit of normal, or those who are symptomatic or at risk for future complications from their disease (alendronate, risedronate, tiludronate) treatment of symptomatic Paget disease (etidronate) treatment of moderate to severe Paget disease (pamidronate). 

Alendronate - Patients with Paget disease or receiving glucocorticoids should receive supplemental calcium and vitamin D if dietary intake is inadequate. 

Paget disease - The recommended dose in patients with moderate to severe Paget disease of bone is 30 mg daily, given as a 4 hour infusion on 3 consecutive days for a total dose of 90 mg. 

Paget disease - 30 mg once daily for 2 months. Retreatment may be considered (following posttreatment observation of 2 months or more) if relapse occurs or if treatment fails to normalize serum alkaline phosphatase. For retreatment, the dose and duration of therapy are the same as for initial treatment. No data are available on more than 1 course of retreatment. 

Paget disease (etidronate) Response may be slow and may continue for months after treatment discontinuation. Do not increase dosage prematurely or initiate retreatment until after at least a 90-day drug-free interval. 

Paget disease Excessive bone formation and resorption (turnover] leads to ineffective remodeling and structural abnormalities within the bone Calcitonin, bisphosphonates... 

General Category Bisphosphonates Examples Alendronate (Fosamax) Etidronate (Didronel) Ibandronate (Boniva) Pamidronate (Aredia) Risedronate (Actonel) Treatment Rationale and Principal Indications Appear to block excessive bone resorption and formation is used to normalize bone turnover in conditions such as osteoporosis and Paget disease, and to prevent hypercalcemia resulting from excessive bone resorption in certain forms of cancer... 

Calcitonin Human calcitonin (Cibacalcin) Salmon calcitonin (Calcimar, Miacalcin) Mimic the effects of endogenous calcitonin and increase bone formation in conditions such as Paget disease and osteoporosis also used to lower plasma calcium levels in hypercalcemic emergencies... 

The polypeptide calcitonin is secreted by thyroid C-cells during imminent hypercalcemia. It lowers elevated plasma Ca2+ levels by inhibiting osteoclast activity. Its uses include hypercalcemia and osteoporosis. Remarkably, calcitonin injection may produce a sustained analgesic effect that alleviates pain associated with bone diseases (Paget disease, osteoporosis, neoplastic metastases) or Sudek syndrome. 

G4. Garnero, P., Fledelius, Ch., Gineyts, E., Serre, C.-M., Vignot, E., and Delmas P. D., Decreased beta-isomerisation of the C-terminal telopeptide of type I collagen alphal chain in Paget disease of bone. J. Bone Miner. Res. 9, 1407-1415 (1997). 

This class of drugs is used to treat hypercalcemia in osteolytic bone cancer and metastasis in breast cancer, multiple myeloma, and Paget disease of the bone. It is used more frequently to inhibit bone resorption in postmenopausal women and therefore has the potential for widespread effects despite a relatively low risk of ADRs. 

CASR SNPs have been associated with a number of complex phenotypes. The Ala986Ser variant has been associated with bone mineral density [18], primary hyperparathyroidism [19], and Paget disease [20],... 

Tumors that are characteristically strongly and diffusely positive include those of the salivary glands, lung, breast, ovary, endometrium, bladder, and thymus, as well as mesotheliomas, neuroendocrine tumors, pancreaticobili-ary adenocarcinomas, and the fibrolamellar variant of hepatocellular carcinoma. 33 CK7 is also typically expressed in tumor cells of mammary and extramammary Paget disease. 34... 

Paget disease occurs in mammary and extramammary (EM) forms. Paget disease of the breast is almost always indicative of an underlying breast carcinoma, whereas EM Paget disease may be an indicator of metastatic carcinoma. 

The presence of CK7+ cells in the nipple epidermis does not equate with Paget disease, including those circumstances in which there is a benign nipple lesion such as nipple adenoma. The presence of benign-appearing CK7+ cells in the epidermis may be a manifestation of the extension of cells from the lactiferous ducts or benign nipple epithelial proliferations into the epidermis. 

The differential diagnosis for Paget disease includes melanoma and Bowen s disease (squamous cell carcinoma), for which appropriate IHC stains could be used. For diagnosing melanoma, at least two melanoma markers should be used because SlOO staining can be seen in up to 18% of breast carcinoma cases. 

The EM forms of Paget disease occur predominantly in females as vulvar or perianal disease but may also occur in males and at other sites. 

Primary vulvar Paget disease is a localized carcinoma of sweat duct origin that may be in situ or invasive histologically, it is composed of large cells with voluminous cytoplasm containing mucin that are universally CK7+ and GCDFP-15+.329... 

Vulvar Paget disease, primary adnexal carcinoma CK7+, CCDFP-15+, CEA+... 

Metastatic colorectal carcinoma presenting as perianal-vulvar Paget disease CK7 (negative), CK20+, CDX2+, CEA+, CCDFP-15 (negative)... 

Ashikari R, Park K, Huvos AG, Urban JA. Paget disease of the breast. Cancer. 1970 26 680-685. 

Salvadori B, Fariselli G, Saccozzi R. Analysis of 100 cases of Paget disease of the breast. Tumori. 1976 62 529-535. 

Meissner K, Riviere A, Haupt G, Toning T. Study of neu-protein expression in mammary Paget disease with and without underlying breast carcinoma and in extramammary Paget disease. Am J Pathol. 1990 137 1305-1309. 

FIGURE 13.6 Extramammary Paget disease of the skin (A) often demonstrates reactivity for gross cystic disease fluid protein-15 (B). 

Malignant melanoma negative for Paget disease markers, HMB-45-, melan-A-, S-100- ... 

Bowen disease AE1/AE3 and K903-I-, negative for Paget disease and melanoma markers... 

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