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These adverse effects can be minimized by starting at lower doses and gradually titrating to full doses as to lerated breast cancer 1 in 8 purchase capecitabine 500 mg line. Addition of bupropion (75 to 150 mg/day in divided doses) or buspirone (10 to 20 mg twice daily) may alleviate decreased libido pregnancy induced carpal tunnel discount 500mg capecitabine with mastercard, diminished sexual arousal breast cancer drug buy 500 mg capecitabine fast delivery, or impaired orgasm breast cancer october purchase capecitabine without prescription. Imipramine (Tofranil) menopause memory loss order capecitabine 500 mg online, a starting dose of 10 to 20 mg po at night can be gradually titrated up to 75 to 300 mg each night menstrual effects order cheap capecitabine online. Desipramine (Norpramin), 25-200 mg qhs, and nortriptyline (Pamelor), 25 mg tid qid, can be used as alternatives. Trazodone (Desyrel) is a sero to nergic agent, but because of its side effects (sedation and priapism), it is not an ideal first-line agent. Daily dosages of 200 to 400 mg are helpful in patients who have not responded to other agents. Nefazodone (Serzone)has a similar pharmacologic profile to trazodone, but it is better to lerated and is a good alternative; 100 mg bid; increase to 200-300 mg bid. However, the onset of action can be several weeks, and there are occasional gastrointestinal side effects. Advantages of using buspirone instead of benzodiazepines include the lack of abuse potential, physical dependence, or with drawal, and lack of potentiation of alcohol or other sedative-hypnotics. Most patients need to be titrated to doses of 30 to 60 mg per day given in two or three divided doses. Many anxious patients who start on benzodiazepines have difficulty s to pping them, particularly since rebound anxiety and withdrawal symp to ms can be moderate to severe. Methods of facilitating withdrawal and decreas ing rebound symp to ms include tapering the medication slowly, converting short-acting benzodiazepines to a long-acting preparation (eg, clonazepam) prior to tapering, and treating the patient with an antidepressant before attempting to taper. After six to eight weeks, when the antidepressant begins to have its optimal effects, the benzodiazepine usually should be tapered over months, achieving roughly a 10 percent dose reduction per week. Benzodiazepines Commonly Prescribed for Anxiety Disorders Name Half-life Dosage Initial dos (hours) range (per age day) Alprazolam 14 1 to 4 mg 0. Agents with short half-lives, such as oxazepam (Serax), do not cause excessive sedation. Agents with long half-lives, such as clonazepam (Klonopin), should be used in younger patients who do not have concomitant medical problems. The longer-acting agents can be taken less frequently during the day, patients are less likely to experience anxiety between doses and withdrawal symp to ms are less severe. Panic Disorder Panic disorder is characterized by the occurrence of panic attacks-sudden, unexpected periods of intense fear or discomfort. Chest pain or discomfort Choking Depersonalization or derealization Dizziness, faintness, or unsteadiness Fear of "going crazy" or being out of control Fear of dying Flushes or chills Nausea or gastrointestinal distress Palpitations or tachycardia Paresthesias Shortness of breath (or feelings of smothering) Sweating Trembling or shaking Diagnostic criteria for panic disorder without ago raphobia Recurrent, unexpected panic attacks And At least one attack has been followed by at least 1 month of one (or more) of the following: Persistent concern about experiencing more attacks Worry about the meaning of the attack or its consequences (fear of losing control, having a heart attack, or "going crazy") A significant behavioral change related to the attacks And Absence of agoraphobia And Direct physiological effects of a substance (drug abuse or medication) or general medical condition has been ruled out as a cause of the attacks And the panic attacks cannot be better accounted for by another mental disorder I. Panic attacks are manifested by the sudden onset of an overwhelming fear, accompanied by feelings of impending doom, for no apparent reason. The essential criterion for panic attack is the presence of 4 of 13 cardiac, neurologic, gastrointestinal, or respira to ry symp to ms that develop abruptly and reach a peak within 10 minutes. The physical symp to ms include short ness of breath, dizziness or faintness, palpitations, accelerated heart rate, and sweating. Trembling, choking, nausea, numbness, flushes, chills, or chest discomfort are also common, as are cognitive symp to ms such as fear of dying or losing control. One third of patients develop agoraphobia, or a fear of places where escape may be difficult, such as bridges, trains, buses, or crowded areas. The his to ry should include details of the panic attack, its onset and course, his to ry of panic, and any treatment. Questioning about a family his to ry of panic disorder, agoraphobia, hypochondriasis, or depression is important. Because panic disorder may be triggered by marijuana or stimulants such as cocaine, a his to ry of substance abuse must be identified. A medication his to ry, including prescrip tion, over-the-counter, and herbal preparations, is essential. The patient should be asked about stressful life events or problems in daily life that may have preceded onset of the disorder. The extent of any avoidance behavior that has developed or suicidal ideation, self-medication, or exacer bation of an existing medical disorder should be assessed. Patients should reduce or eliminate caffeine consump tion, including coffee and tea, cold medications, analgesics, and beverages with added caffeine. Alcohol use is a particularly insidious problem because patients may use drinking to alleviate the panic. Fluoxetine (Prozac), fluvoxamine (LuVox), paroxetine (Paxil), sertraline (Zoloft), and citalopram (Celexa) have shown efficacy for the treatment of panic disorder. They are, however, associated with a delayed onset of action and side effects-particu larly orthostatic hypotension, anticholinergic effects, weight gain, and cardiac to xicity. Clonazepam (Klonopin), alprazolam (Xanax), and lorazepam (Ativan), are effective in blocking panic attacks. Advantages include a rapid onset of therapeu tic effect and a safe, favorable, side-effect profile. Among the drawbacks are the potential for abuse and dependency, worsening of depressive symp to ms, withdrawal symp to ms on abrupt discontinuation, anterograde amnesia, early relapse on discontinua tion, and inter-dose rebound anxiety. Benzodiazepines are an appropriate first-line treatment only when rapid symp to m relief is needed. Approximately 70% of patients will experience a discontinuance reaction characterized by increased anxiety, agitation, and insomnia when alprazolam is tapered. Beta-blockersare useful in moderating heart rate and decreasing dry mouth and tremor; they are less effective in relieving subjective anxiety. Insomnia Insomnia is the perception by patients that their sleep is inadequate or abnormal. Younger persons are apt to have trouble falling asleep, whereas older persons tend to have prolonged awakenings during the night. Patients under stress may experience interference with sleep onset and early morning awakening. Attempting to sleep in a new place, changes in time zones, or changing bedtimes due to shift work may interfere with sleep. Drugs associated with insomnia include antihypertensives, caffeine, diuretics, oral contraceptives, pheny to in, selective sero to nin reuptake inhibi to rs, protrip tyline, corticosteroids, stimulants, theophylline, and thyroid hormone. Depression is a common cause of poor sleep, often characterized by early morning awak ening. Associated findings include hopelessness, sadness, loss of appetite, and reduced enjoyment of formerly pleasurable activities. Prostatism, peptic ulcer, congestive heart failure, and chronic obstructive pulmonary disease may cause insomnia. Pain, nausea, dyspnea, cough, and gastroesophageal reflux may interfere with sleep. It is characterized by recurrent discontinuation of breathing during sleep for at least 10 seconds. Abnormal oxygen saturation and sleep patterns result in excessive daytime fatigue and drowsiness. Use of hypnotic agents is contraindicated since they increase the frequency and the severity of apneic episodes. Acute personal and medical problems should be sought, and the duration and pattern of symp to ms and use of any psychoactive agents should be investigated. Substance abuse, leg movements, sleep apnea, loud snoring, nocturia, and daytime napping or fatigue should be sought. Consumption of caffeinated beverages, prescribed drugs, over-the-counter medications, and illegal substances should be sought. These drugs include the benzodiazepines and the benzodiazepine recep to r agonists in the imidazopyridine or pyrazolopyrimidine classes. Recommended dosages of hypnotic medications (elderly dosages are in parentheses) Benzodiaz Recom Tmax Elimi Re epine mended nation cep to hypnotics dose, mg half r se life lectiv ity Benzodiazepine recep to r agonists Zolpidem 5-10 (5) 1. Zolpidem (Ambien) and zaleplon (Sonata) have the advantage of achieving hypnotic effects with less to lerance and fewer adverse effects. The safety profile of these benzodiazepines and benzodiazepine recep to r agonists is good; lethal overdose is rare, except when benzodiazepines are taken with alcohol. Sedative effects may be enhanced when benzodiazepines are used in conjunction with other central nervous system depressants. Zolpidem (Ambien)is a benzodiazepine agonist with a short elimination half-life that is effective in inducing sleep onset and promoting sleep maintenance. Zolpidem may be associated with greater residual impairment in memory and psychomo to r performance than zaleplon. Zaleplon does not impair memory or psychomo to r functioning at as early as 2 hours after administration, or on morning awakening. Zaleplon does not cause residual impairment when the drug is given in the middle of the night. Zaleplon can be used at bedtime or after the patient has tried to fall asleep naturally. Benzodiazepines with long half-lives, such as flurazepam (Dalmane), may be effective in promoting sleep onset and sustaining sleep. These drugs may have effects that extend beyond the desired sleep period, however, resulting in daytime sedation or functional impairment. Patients with daytime anxiety may benefit from the residual anxiolytic effect of a long-acting benzodiazepine administered at bedtime. Benzodiazepines with intermediate half-lives, such as temazepam (Res to ril), facilitate sleep onset and mainte nance with less risk of daytime residual effects. Benzodiazepines with short half-lives, such as triazolam (Halcion), are effective in promoting the initiation of sleep but may not contribute to sleep mainte nance. Sedating antidepressantsare sometimes used as an alternative to benzodiazepines or benzodiazepine recep to r agonists. Amitriptyline (Elavil), 25-50 mg at bedtime, or trazodone (Desyrel), 50-100 mg, are common choices. Nicotine Dependence Smoking causes approximately 430,000 smoking deaths each year, accounting for 19. The symp to ms include craving for nicotine, irritability, frustration, anger, anxiety, restlessness, difficulty in concentrating, and mood swings. Treatment with nicotine is the only method that produces significant withdrawal rates. Nicotine patches provide steady-state nicotine levels, but do not provide a bolus of nicotine on demand as do sprays and gum. Bupropion (Zyban) is an antidepressant shown to be effective in treating the craving for nicotine. The symp to ms of nicotine craving and withdrawal are reduced with the use of bupropion, making it a useful adjunct to nicotine replace ment systems. A 2-mg dose is recommended for those who smoke fewer than 25 cigarettes per day, and 4 mg for heavier smokers. It provides a plateau level of nicotine at about half that of what a pack-a-day smoker would normally obtain. Nicotine inhaler (Nicotrol Inhaler) delivers nicotine orally via inhalation from a plastic tube. It is available by prescription and has a success rate of 28%, similar to nicotine gum. The inhaler has the advantage of avoiding some of the adverse effects of nicotine gum, and its mode of delivery more closely resembles the act of smoking. Bupropion is appropriate for patients who have been unsuccessful using nicotine replacement. Bupropion reduces withdrawal symp to ms and can be used in conjunction with nicotine replacement therapy. Bupropion is contraindicated with a his to ry of seizures, anorexia, heavy alcohol use, or head trauma. Bupropion is started at a dose of 150 mg daily for 3 days and then increased to 300 mg daily for 2 weeks before the patient s to ps smoking. When a nicotine patch is added to this regimen, the abstinence rates increase to 50% compared with 32% when only the patch is used. Anorexia Nervosa Anorexia nervosa is a psychologic illness characterized by marked weight loss, an intense fear of gaining weight even though the patient is underweight, a dis to rted body image and amenorrhea. The typical patient with anorexia nervosa is an adoles cent female who is a high achiever. She is a perfectionist and a good student, involved in many school and community activities. Persons with anorexia nervosa have a disturbed perception of their own weight and body shape. A trial of outpatient treatment may be attempted if the patient is not severely emaciated, has had the illness for less than six months, has no serious medical complica tions, is accepting her illness and is motivated to change, and has supportive and cooperative family and friends. The first step in the treatment of anorexia nervosa is correction of the starvation state. A caloric intake to provide a weight gain of 1 to 3 lb per week should be instituted. Initially, weight gain should be gradual to prevent gastric dilation, pedal edema and congestive heart failure. Often, a nutritional supplement is added to the regimen to augment dietary intake. During the process of refeeding, weight gain as well as electrolyte levels should be strictly moni to red. The dis turbed eating behavior must be addressed in specific counseling sessions.

Syndromes

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A number of nutritional and dietary supplements were investigated to relieve symp to ms menstruation vaginal itching purchase genuine capecitabine online. Results of some studies suggest that eliminating caffeine from the diet is associated with improvement of symp to ms (100 menstruation and pregnancy order capecitabine 500mg visa,101) menstrual girls photos purchase generic capecitabine on line. Many patients are aware of these studies and report relief of symp to ms after discontinuing intake of coffee omega 7 menopause buy 500mg capecitabine, tea 9gag menstrual cycle best buy for capecitabine, and chocolate menstrual 9gag cheap 500 mg capecitabine. A recent review of nutritional interventions for fibrocystic breast conditions that evaluated evening primrose oil, vitamin E, or pyridoxine suggested that there are insufficient data to draw clear conclusions about their effectiveness (107). Exacerbations of pain, tenderness, and cyst formation may occur at any time until menopause, when symp to ms usually subside unless patients are taking estrogen. A patient with fibrocystic changes should be advised to examine her own breasts each month just after menstruation and to inform her physician if a mass appears. Mastalgia Mastalgia is a recognized organic condition that is studied less thoroughly than other breast problems (108,109). A study evaluating expression of interleukin-6 and tumor necrosis fac to r-fi in painful and nonpainful breast tissue showed lower levels of these cy to kines in painful breast tissue during the luteal phase; however, these levels did not reach statistical significance (110). Elevated estrogen, low progesterone, or an imbalance in the ratio of estrogen and progesterone were suggested as a possible cause for the symp to ms (111). Natural His to ry of Mastalgia Approximately 70% to 80% of women experience severe breast pain at some time in their lives (112,113). In 15% of the patients, the mastalgia is so severe that it alters lifestyle and requires repeated investigations and treatment (112). Mastalgia interferes with sexual (48%), physical (37%), social (12%), and work or school activities (8%) (115). Types of Mastalgia Breast pain is a distressing constellation of symp to ms that is classified as cyclic, noncyclic, or extramammary (116). Cyclical mastalgia is more prevalent in women in their third and fourth decades of life and accounts for two-thirds of all breast pain symp to ms (119). Noncyclic mastalgia is independent of menstrual cycles and is described as achy, burning soreness. It may be intermittent or constant, is usually unilateral, occurs in the fourth and fifth decades, and is more difficult to treat than cyclic mastalgia (116). Extramammary pain is perceived to be located in the breast but is related to an extramammary site. Chest wall muscular pain, costal cartilage symp to ms, herpes zoster, radiculopathies, and rib fractures are among some of the more common causes of extramammary pain. Cos to chondritis (Tietze syndrome) is a manifestation of chest wall pain that is frequently interpreted as breast pain. Management of Mastalgia Breast pain is an unlikely symp to m of malignancy, and when malignancy is excluded by a clinical breast examination and age-appropriate breast imaging for focal breast pain, the most important treatment is reassurance. Treatments include medications, such as anesthetics, diuretics, bromocriptine, and tamoxifen; vitamins and supplements, such as evening primrose oil; mechanical support with a well fitting bra; local excision; and decreased fat intake and reduction in methylxanthines from caffeine, tea, and chocolate (108,116). Maintenance of a pain score diary is important to understand the relationship of pain to fac to rs such as the menstrual cycle, activities of daily living, and stress. External support may be effective for breast pain associated with generalized fibrocystic changes and is best treated by avoiding trauma and by wearing (night and day) a brassiere that gives good support and protection (120). One study evaluated resolution of symp to ms in 200 women randomized either to a regimen of danazol (200 mg per day) or to mechanical support with a sports brassiere worn for regular activities for 12 weeks. The group using mechanical support had 85% relief of symp to ms compared with 58% improvement in the danazol group. The danazol group experienced drug-related side effects in 42%, which led to discontinuance of the medication in 15%. The breast has minimal structural support and is at significant risk for motion-related displacement resulting in mastalgia. The use of external support to minimize breast motion appears to be effective in reducing breast pain. The application of heat packs or cold packs and light breast massage may reduce symp to ms in some individuals (116). These drugs are associated with significant side effects that limit their general use (116). Withdrawal of birth control pills or hormone therapy may be all that is required to alleviate symp to ms (116). Danazol is a synthetic androgen that suppresses release of pituitary gonadotropin, prevents luteinizing hormone surge, and inhibits ovarian steroid formation. It can be initiated at doses of 100 to 200 mg twice daily orally for patients with severe pain and then tapered to a lower dose of 100 mg per day (122). A survey of surgeons in Great Britain revealed that 75% prescribed danazol as first-line therapy (108). A study conducted to evaluate the response to administration of danazol revealed a 79% amelioration of symp to ms (125). This approach reduced the premenstrual mastalgia and resulted in virtually no side effects. Further studies may be warranted to see whether medroxyprogesterone acetate suppresses cyclic mastalgia in reproductive-age women. A randomized, double-blind study with supraphysiologic levels of iodine in women with documented cyclic mastalgia demonstrated dose-dependent reduction in physician-assessed and self-reported pain at 3 and 6 months of treatment (130). Side effects of goserelin include vaginal dryness, hot flushes, decreased libido, oily skin and hair, and decreased breast size. A recent clinical trial randomized 147 women in to goserelin versus placebo groups. The mean breast pain score decreased by 67% in the goserelin arm and 35% in the placebo arm. The authors concluded that goserelin is an effective treatment for mastalgia with significant side effects and should be kept as second-line therapy. Hormonal blockade of the estrogen recep to r is another approach to minimizing the effects of circulating estrogen on breast pain. There was a significant reduction in cyclic and noncyclic pain in all groups, but the magnitude of change was greater in the treatment arms and similar for cyclic and noncyclic pain. Nonhormonal therapies such as dietary restrictions, vitamins and supplements, and restriction of methylxantines were investigated as possible treatments for mastalgia because they are less likely to be associated with adverse drug-related side effects (116). Because mastalgia is one of the symp to ms associated with fibrocystic disease, the treatments described for fibrocystic disease are relevant to mastalgia. Ninety percent of patients taking in 15% dietary fat experienced resolution of pain symp to ms after 6 months compared with only 22% of those on a diet containing 36% fat (p =. It was used as first-line therapy, reserving danazol and bromocriptine for treatment of more severe symp to ms (112). Those who responded had a lower level of essential fatty acids at the time of initiation when compared with poor responders, suggesting that evening primrose oil increases essential fatty acids and that this increase may be associated with the improvement in symp to ms in the responders. Two other trials failed to demonstrate efficacy of evening primrose oil capsules over placebo (139,140). In a Dutch trial, 124 women with cyclic or noncyclic pain lasting on average 7 or more days (minimum 5 days) were randomized to receive the following regimens: (i) fish oil and control oil, (ii) evening primrose oil and control oil, (iii) fish and evening primrose oil, or (iv) both control oils for 6 months (139). There was a statistically significant reduction in the number of days per month with pain but not in the pain score in the entire study population. There was a greater reduction in cyclic than noncyclic pain symp to ms, and this finding was true for both the test oils and for the control oils. The authors concluded that neither fish oil nor evening primrose oil had a better effect than the less expensive wheat germ and corn oils. A second large double-blind randomized prospective trial was conducted in 555 women with cyclic mastalgia of moderate to severe degree present for at least 7 days of a menstrual cycle (140). There was continued improvement of symp to ms in all groups with a reduction in mastalgia by 50% over the next 12 months. The results of this study were not consistent with those from previous smaller studies. The randomized trials, however, bring in to serious question the efficacy of these options. Fibroepithelial Lesions Fibroadenoma Fibroadenomas are the most common benign tumors of the breast. They usually occur in young women (age 20 to 35 years) and may occur in teenagers (142). They rarely occur after menopause, although occasionally they are found, often calcified, in postmenopausal women. For this reason, it is postulated that fibroadenomas are responsive to estrogen stimulation. A study reports the de novo occurrence of fibroadenoma in 51 women older than age 35 years who had no evidence of a palpable or mammographic visualized lesion in well documented prior visits (143). Most masses are 2 to 3 cm in diameter when detected, but they can become extremely large. They do not elicit an inflamma to ry reaction, are freely mobile, and cause no dimpling of the skin or nipple retraction. On mammographic and ultrasonographic imaging, the typical features are of a well-defined, smooth, solid mass with clearly defined margins and dimensions that are longer than wide and craniocaudad dimensions that are less than the length. The natural his to ry of fibroadenoma can be regression, growth, or no change in size. Most fibroadenomas are static or cease growth at approximately 2 to 3 cm, about 15% of tumors regress spontaneously, and only 5% to 10% progress (145). Because transformation of a fibroadenoma in to cancer is rare and regression is frequent, current management recommendations are conservative unless there is evidence of growth (141). Complete excision of a fibroadenoma with local anesthesia can be performed to treat the lesion and confirm the absence of malignancy. Less invasive local treatment of a fibroadenoma is advocated by some and can be performed with either ultrasonographically guided percutaneous vacuum-assisted biopsy devices or percutaneous cryoablation (146,147). A young woman with a clinical fibroadenoma can undergo needle cy to logy and observation of the mass (148). Acceptance of observation varies, and many women choose to have the fibroadenoma excised (149). On gross examination of an excised mass, the fibroadenoma appears encapsulated and sharply delineated from the surrounding breast parenchyma. Microscopically, there is proliferation of both the epithelial and stromal component. In longstanding lesions and in postmenopausal patients, calcifications may be observed within the stroma. Excision of all lesions through separate incisions could leave significant scarring and deformity. Excision of these mobile lesions through a single periareolar incision was suggested, but this approach can lead to significant ductal disruption (153). Phyllodes Tumor Phyllodes tumors are rare fibroepithelial tumors that display a spectrum of clinical and pathologic behaviors that are benign, borderline, and malignant (154,155). The distribution of phyllodes tumors demonstrates that most tumors are benign (70%) compared with malignant (23%) and borderline lesions (7%) (156). This distribution is similar to a larger, older study that reported an incidence of 64% benign, 21% malignant, and 14% borderline phyllodes tumors (157). The incidence in some studies should be viewed with caution because of variation in his to logic interpretation (156). These lesions are rarely bilateral and usually appear as isolated masses that are difficult to distinguish clinically from a fibroadenoma. Patients often relate a long his to ry of a previously stable nodule that suddenly increases in size. Size is not a dependable diagnostic criterion, although phyllodes tumors tend to be larger than fibroadenomas, probably because of their rapid growth. There are no good clinical criteria by which to distinguish a phyllodes tumor from a fibroadenoma. Whereas observation of a fibroadenoma is acceptable, excision of a phyllodes tumor is necessary for local control and for determination of benign or malignant features. Ultrasonography evaluation has limitations even when color and pulse Doppler ultrasonography are used in conjunction with it (163). It may be easier to distinguish benign phyllodes from malignant phyllodes tumors than benign phyllodes tumors from fibroadenomas (170).

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Neoplasms composed of Hurthle cells are still controversial with regard to their classification and biologic behaviour pregnancy yoga classes cheap capecitabine online american express. Some consider it a subtype of follicular neoplasm and the criteria for differentiating benign from malignant are the same as in the other follicular tumours women's health recipe finder purchase cheap capecitabine online, including demonstration of invasion menstruation occurs in response to cheap capecitabine line. Others women's gynecological health issues cheap capecitabine online amex, however menopause emedicine buy capecitabine 500 mg overnight delivery, consider thyroid neoplasms composed of this cell type as a separate entity with different pathologic and behavioural features [2 breast cancer epidemiology purchase capecitabine 500 mg without prescription. Most studies recognize benign and malignant forms, with invasion as the most important determining fac to r. Papillary carcinoma Papillary carcinoma is the most common type of thyroid cancer. It is a malignant epithelial tumour with evidence of follicular cell differentiation forming papillae and/or a set of distinctive nuclear features [2. The tumour is multifocal in 18 22% of cases, and metastasizes more frequently to regional cervical lymph nodes than to distant sites [2. Grossly, the papillary nature of the tumour may be suspected from the granular surface (Fig. The margins are ill-defined, and calcifications are indicated by a gritty sensation imparted to the cutting knife. The coarsely granular surface reflects the microscopic morphologic features of branching processes. Branching processes composed of fibrovascular stalks supporting low columnar cells with optically clear nuclei (inset). Papillary carcinoma variants Occult sclerosing papillary tumour (papillary microcarcinoma). To be classified under this category, most pathologists agree that the papillary neoplasm should measure 1 cm. It may show a to tally follicular or a mixed follicular and papillary architecture, with the distinctive nuclear characteristics of papillary carcinoma. Like conventional papillary carcinoma, cervical lymph node metastases are common, and the nodal metastases may show a more obvious papillary pattern. Most cases share many features of classic papillary carcinoma, including multicentric occurrence and its propensity to metastasize to cervical lymph nodes. However, some behave in an aggressive manner, metastasizing through the haema to genous route to distant sites [2. The tall cell variant of papillary carcinoma makes up approximately 10% of thyroid cancers, tend to occur in the older age group, and is usually large (more than 5 cm. The papillae are lined by cells that are twice as tall as they are wide, containing abundant eosinophilic cy to plasm superficially resembling oncocytes. This variant has a more aggressive clinical behaviour than the classic papillary thyroid carcinoma [2. The columnar cell variant differs from the tall cell variant from the presence of nuclear stratification. It may show clearing of the cy to plasm resembling subnuclear vacuolation in early secre to ry phase endometrium. This subtype of papillary carcinoma is characterized by a diffuse involvement of one, or more commonly both, lobes of the thyroid gland by multiple papillary formations within intrathyroid spaces probably representing lymphatic spaces, with tendency to be associated with squamous metaplasia, and many psammoma bodies. In contrast to the 13 conventional papillary carcinoma, this variant has a higher incidence of cervical nodal metastasis, a greater incidence of pulmonary metastasis, and a lesser probability of disease free survival on follow-up [2. Poorly differentiated carcinoma Insular carcinoma is the term proposed by Carcangiu, et al. It is an aggressive neoplasm associated with regional and distant metastases and a high mortality rate [2. The prognosis is worse than well differentiated follicular carcinoma and better than anaplastic carcinoma. This is a highly malignant neoplasm that is partly or to tally undifferentiated, but shows evidence of epithelial differentiation based on morphologic, immunohis to chemical, or ultrastructural grounds [2. There is a wide spectrum of his to logic appearances, but most assume squamoid, spindle cell, and giant cell patterns (Fig. Neither extent of operation nor completeness of resection has affected survival, and multimodal therapy (surgery, chemotherapy, and radiotherapy) has not improved the high mortality rate [2. Marked pleomorphism associated with hemorrhage, necrosis, and osteoclast-like multinucleated giant cells scattered among the neoplastic cells. It is interesting to note that patients with familial medullary 14 carcinoma diagnosed by screening (genetic and/or biochemical) and treated early, had a lower incidence of cervical lymph node metastasis and nearly a 100% cure rate [2. Early detection not only of hereditary but even of sporadic medullary thyroid carcinoma by means of calci to nin screening programs permits curative surgery in majority of patients [2. Architectural patterns include trabecular, follicular, tubular, and cell nests with carcinoid appearance. The tumour is composed of spindly cells with moderate amount of eosinophilic cy to plasm, some assuming plasmacy to id appearance. Prognosis of medullary carcinoma is related to the following pathologic features: tumour pattern, necrosis, presence of amyloid [2. Malignant lymphoma of the thyroid gland may occur as part of a systemic lymphoma, or may arise as a primary non-epithelial neoplasm. It is estimated that the risk of malignant lymphoma developing in a patient with lymphocytic thyroiditis is 40-80 times greater than in the general population. Summary the morphologic features of the different types of thyroid cancer have been reviewed, including prognostic fac to rs and recent advances in ancillary procedures which aid in a more precise his to logical typing. Continuing studies will undoubtedly contribute to more precise diagnosis, earlier treatment with improved cure rates, and even prevention of occurrence of certain thyroid malignancies, particularly those associated with genetic fac to rs in their pathogenesis. The most common presentation is the incidental, asymp to matic, small, solitary nodule, in which the exclusion of cancer is the major concern. Regional metastatic lymphadenopathy in the neck is rare in adults but is fairly common among children. Rarely, it may present as a large mass, partly retrosternal nodule that causes pressure symp to ms or it may present as hoarseness of voice due to infiltration or compression of recurrent laryngeal nerve. The prevalence of thyroid nodule varies from country to country, and more so depends on the environmental iodine status. In the United States, which is an iodine sufficient environment, 4 to 7 per cent of the adult population has a palpable thyroid nodule [3. This corresponds to approximately 2 to 4 per 100 000 people per year, constituting only 1 per cent of all cancers and 0. The prevalence is much greater with the inclusion of nodules that are detected by ultrasonography or at au to psy. By the latter assessment, approximately 50 per cent of 60-year old persons have thyroid nodules [3. The natural his to ry of solitary thyroid nodules is poorly unders to od, mainly because nodules that are suspicious for cancer, cause pressure, or produces cosmetic problems are rarely left untreated. With this reservation, it seems that the majority of benign non-functioning nodules also grow, particularly those that are solid [3. In one study, 89 per cent of nodules that were followed for five years increased by 15 per cent or more in volume [3. The most common diagnoses are colloid nodules, cysts, and thyroiditis approximately in 80 per cent of cases; follicular neoplasms in 10 to 15 per cent; and thyroid carcinoma in 5 per cent. The solitary thyroid nodule that is detected on physical examination, regardless of the finding of additional nodules by radionuclide scanning or ultrasonography has equal probability of malignancy, since such a finding does not alter the risk of cancer [3. The risk of thyroid cancer seems nearly as high in incidental nodules (<10 mm), the majority of which escape detection by palpation, as in larger nodules [3. However, the vast majorities of these microcarcinomas do not grow during long term follow-up and do not cause clinically significant thyroid cancer [3. His to ry and physical examination the his to ry and physical examination remain the diagnostic corners to nes in evaluating the patient with a thyroid nodule and may be suggestive of thyroid carcinoma. However, a very few of patients with malignant nodules have suggestive findings, which often also occur in patients with benign thyroid disorders. The fact that ultrasonography detects nodules a third of which are more than 20 mm in diameter in up to 50 18 per cent of patients with a normal neck examination underscores the low specificity and sensitivity of clinical examination [3. When two or more risk fac to rs that indicate a high clinical suspicion are present, the likelihood of cancer approaches 100 per cent [3. Intrathyroid papillary carcinomas and microangioinvasive follicular carcinomas are very slow growing tumours in patients under the age of forty. This applies also to metastases, which may not be clinically apparent until five to ten or more years after initial thyroidec to my. Such metastases tend to occur either in the lymph nodes (papillary) or in bones (follicular). After the age of forty years, previously diagnosed and newly diagnosed tumours show a tendency to grow and spread more rapidly, usually associated with less well-differentiated his to pathology. Hurthle cell carcinoma, which is considered to be a variant of follicular cancer presents as bulky and invasive tumour and behave fairly aggressive manner, metastasize widely and prove lethal in a high proportion of patients. They also present as solitary nodules th predominantly in the 6 decade of life and with sizes over 4 cm. The course is variable and the tumour tends to be slowly progressive metastasizing early to the cervical lymph nodes. The sporadic type is commonly unilateral, occurs early in life and is rapidly progressive in type 2B disease. The 19 th th familial type is almost always bilateral and may present as a nodule in the 5 and 6 decades. Fifty per cent on presentation are localized and 10% as distant spread and 10% with pressure symp to ms. Facial flushing, diarrhoea and elevated calci to nin levels are typical features of the disease. Anaplastic carcinoma accounts for 1-2% of thyroid cancer and present as a his to ry of recent, very rapid enlargement of a normal or goitrous thyroid gland, with local pressure symp to ms, particularly difficulty in breathing. On examination, the thyroid is asymmetrically enlarged or with a large hard mass that is fixed to the underlying structures. Frequently, there is a his to ry of a pre-existing goitre and a his to ry of long standing thyroid enlargement in about 80% of patients. There may also be a previous his to ry of well differentiated thyroid cancer with sudden fulminant disease. It is highly fatal and spreads locally involving the trachea, oesophagus and superior mediastinum by direct extension. This is the most aggressive form of thyroid cancer and affects the older age group usually over 70 years old. They may present with dysphagia, a painful neck mass or as a superior vena caval syndrome. This may also be the picture of the other undifferentiated thyroid carcinomas as in lymphomas, squamous carcinomas, giant and small cell carcinomas, sarcomas and mucoepidermoid carcinoma of the thyroid. It is usually painless though pain may occur if there is haemorrhage in the nodule but is rare. Pain may be the presenting feature of anaplastic thyroid cancer when there is rapid growth of the nodule over weeks that stretch the capsule causing pain or there is 20 invasion in to the skin. The patient may have noticed it incidentally or someone else may have pointed out a swelling in the neck. The swelling may be slowly growing over months or years or rapidly growing over weeks. The general approach to the diagnosis of a solitary thyroid nodule is described in later section and will not be repeated here. Thyroid cancer, usually of the follicular variety may arise in a long standing multi-nodular goitre. A patient with recurrence of disease following treatment may also complain of swelling in the neck in the thyroid bed. Lymph node enlargement: Although microscopic metastasis can be found in up to 50% of cases, palpable lymph node enlargement is much less common though of extreme clinical significance from the points of view of staging and treatment. Nodes in the anterior triangle are more clinically significant than those in the posterior triangle. Findings due to loco-regional spread Invasion in the surrounding structures, which is recurrent laryngeal nerve, trachea, strap muscles of the neck, or oesophagus, may occur. The patient may present with hoarseness of voice, difficulty in breathing or strider, or dysphagia. Superior Vena Cava Syndrome may arise due to spread along the blood vessels in follicular cancer or due to external compression in the case of anaplastic cancer. Bone metastasis: Thyroid cancer may spread to appendicular skele to n, skull including base of skull, spine or pelvis. The patient may present with a swelling or a pathological fracture in the case of appendicular skele to n metastasis. In a patient with a pathological fracture of the humerus or femur with an unknown cause, thyroid gland must be carefully examined. A patient may present with diplopia, prop to sis or difficulty in swallowing due to base of skull metastasis. Widespread skeletal metastasis can be extremely painful needing significant attention to pain palliation therapy. Brain Metastasis: Though rare, a patient with brain metastasis from thyroid cancer may present with or develop features of raised intracranial tension that is, persistent headache, early morning vomiting, diplopia and papilledema [3. Also, in a patient with brain metastasis from an unknown primary, thyroid gland must be carefully examined as it makes the disease potentially treatable.

Diseases

References