Clinical aspects and diagnostic relevance of neuroautonomic evaluation in patients with unexplained falls.

OBJECTIVE: To evaluate the diagnostic relevance of neuroautonomic evaluation in patients with unexplained falls compared to those with a syncope etiologically unexplained after initial evaluation. METHODS: It is an observational study, comparing 298 patients with unexplained fall with 989 patients with unexplained syncope. Each patient underwent supine and upright blood pressure measurement, tilt testing (TT) and carotid sinus massage (CSM). RESULTS: Patients with unexplained falls were older (75.3 ± 11.1 vs. 63.2 ± 19.2 years, p < 0.001), were more frequently hypertensive (66.1 vs. 47.2 %, p < 0.001) and more frequently prescribed antihypertensive drugs (62.4 vs. 48.7 %, p < 0.001) or benzodiazepines (15.7 vs. 10.6 %, p = 0.01), and in a greater proportion they experienced major traumatic injuries (77.5 vs. 29.6 %, p < 0.001) as a consequence of falls. The TT was less frequently positive in patients with unexplained falls (36 vs. 51.3 %, p < 0.001), whereas a Carotid Sinus Syndrome as suggested by CSM had a similar prevalence in the two groups (14.3 vs. 10.5 %, p = 0.074). Overall, either TT or CSM were positive in 61 % of patients with unexplained falls, and in 64 % of those with syncope (p = 0.346). After matching by age 298 patients with falls (75.3 ± 11.1 years) and 298 patients with unexplained syncope (75.4 ± 11.1 years), we found that the positivity prevalence of TT and CSM were similar in the two groups. CONCLUSIONS: The positivity prevalence of TT and CSM in patients with unexplained falls compared to patients with unexplained syncope is similar. Given its high diagnostic relevance, the neuroautonomic evaluation should be routinely performed in older patients with unexplained falls.

The management of syncope in older adults.

Syncope is a frequent symptom in older patients. The diagnostic and therapeutic management may be complex, particularly in older adults with syncope and comorbidities or cognitive impairment. Morbidity related to syncope is more common in older persons and ranges from loss of confidence, depressive illness and fear of falling, to fractures and consequent institutionalization. Moreover, advan-ced age is associated with short and long-term morbidity and mortality after syncope. A standardized approach may obtain a definite diagnosis in more than 90% of the older patients with syncope and may reduce diagnostic tools and hospitalizations. The initial evaluation, including anamnesis, medical examination, orthostatic hypotension test and electrocardiogram (ECG), may be more difficult in the elderly, specially for the limited value of medical history, particularly for the certain diagnosis of neuro-mediated syncope. For this reason neuroautonomic assessment is an essential step to confirm a suspect of neuromediated syncope. Orthostatic blood pressure measurement, head up tilt test, carotid sinus massage and insertable cardiac monitor are safe and useful investigations, particularly in older patients. The most common causes of syncope in the older adults are orthostatic hypotension, carotid sinus hypersensitivity, neuromediated syncope and cardiac arrhythmias. The diagnostic evaluation and the treatment of cardiac syncope are similar in older and young patients and for this reason will not be discussed. In older patients unexplained falls could be related to syncope, particularly in patients with retrograde amnesia. There are no consistent differences in the treatment of syncope between older and younger population, but a specific approach is necessary for orthostatic hypotension, drug therapy and pacemaker implantation.

Long-term results of combined modality therapy in primary bone lymphomas.

PURPOSE: To report the Massachusetts General Hospital experience in the management of patients with primary bone lymphoma (PBL) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Records from 37 eligible patients were reviewed. Two patients were treated with complete resection of the tumor, while 35 patients underwent radiation therapy with a median total dose of 54 Gy (range 38.35-66.5). All patients received combination chemotherapy, which contained doxorubicin in 33 cases. We compared the current data with our previous experience in patients treated with local measures only. RESULTS: Actuarial disease-free survival (DFS) at 5 and 10 years is 78% and 73%, respectively, while overall survival (OS) is 91% and 87%, respectively. No local failures were seen. Pathologic fracture at presentation influenced DFS (p = 0.005) and OS (p = 0.017) adversely. OS was compromised in patients older than 60 years (p = 0.059) and DFS in patients with pelvic primaries (p = 0.015). CMT was associated with improved DFS (p = 0.0008) and OS p = 0.0001) compared to our historical controls. Ten patients (27%) developed complications requiring orthopedic procedures following completion of therapy at a median of 25.5 months (range 4-228). CONCLUSION: Patients with PBL have a favorable outcome with CMT, which appears superior to radiation therapy alone. Late complications can be seen, especially in weight-bearing bones.

Metaplastic carcinoma of the breast with melanocytic differentiation.

We report the clinical and pathologic findings of a metaplastic carcinoma of the breast that exhibited melanocytic differentiation. The tumor possessed both in situ and invasive components. Lower grade regions of the infiltrating carcinoma had features of tubular, mucinous, and matrix-producing carcinomas. In the higher grade areas, conventional poorly differentiated ductal carcinoma merged with an anaplastic neoplasm that looked like malignant melanoma. The nonpigmented cells stained for keratin but lacked HMB-45 and S-100 proteins, whereas the cells containing melanin showed the opposite characteristics. Electron microscopic examination disclosed melanosomes in the neoplastic cells. We believe that these observations convincingly establish both the origin of the tumor from the mammary epithelium and the synthesis of melanin by the tumor cells. We propose the diagnosis of metaplastic carcinoma with melanocytic differentiation for this neoplasm and suggest that the phenomenon of melanocytic metaplasia might underlie the formation of primary melanomas of the breast.

Sertoli-Leydig cell tumor of the ovary: a case report with endocrinologic observations.

OBJECTIVE: To present a case of a Sertoli-Leydig cell ovarian tumor and discuss the endocrinologic findings. METHODS: We describe the clinical manifestations in a female patient with an ovarian tumor and summarize the results of hormonal studies. RESULTS: A 33-year-old woman with abrupt cessation of menses, progressive hirsutism, and weight gain because of a unilateral ovarian mass identified sonographically and an increased serum testosterone level underwent laparotomy, which disclosed a left ovarian Sertoli-Leydig cell tumor. Hysterectomy and bilateral adnexectomy were performed. Tissue extraction studies revealed 17-hydroxyprogesterone as the predominant steroid in tumor tissue in conjunction with substantially increased testosterone, free testosterone, dihydrotestosterone, androstenedione, and dehydroepiandrosterone levels and left ovarian vein effluent. CONCLUSION: A unilateral ovarian mass associated with substantially increased serum testosterone should suggest the presence of a functioning ovarian tumor. Androgenic symptoms are a consequence of disturbed steroidogenesis from multipotential steroidogenic cells of ovarian stromal origin whose clinical effects depend on enzymatic specificity and the relative concentrations of steroids produced.

Spindle cell endocrine carcinoma of the mammary gland.

We report the pathological characteristics of a variant of mammary endocrine tumour, predominantly formed from cytologically bland spindle cells. This neoplasm grows as a red, well defined mass lacking the usual macroscopical characteristics of breast cancer. Within smoothly contoured aggregates arranged in an insular pattern, delicate capillaries and collagen bundles support the neoplastic epithelial cells. Most of the tumour cells possess a slender spindle shape and form a solid or fenestrated sheet, but a few appear cuboidal and create glands. Immunohistochemical studies demonstrate that the spindle cells and the glandular cells constitute a single population. Both types of cells stain for neuroendocrine markers (chromogranin, synaptophysin, and CD 57), carcinoembryonic antigen, keratin 8/18, S-100 protein, and receptors for oestrogen and progesterone. Many of the tumour cells possess argyrophilic granules, and electron microscopy may reveal dense core granules.

Basal cell carcinoma of the vulva with groin node metastasis.

There have been five previous well-documented cases of metastatic vulvar basal cell cancer in the literature. We now present the sixth case-an 86-year-old patient with vulvar basal cell cancer metastatic to an ipsilateral groin node. She was treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy and remains free of disease 1 year later.

A comparative study of radical vulvectomy and modified radical vulvectomy for the treatment of invasive squamous cell carcinoma of the vulva.

Forty-five patients who underwent a modified radical vulvectomy for invasive squamous cell carcinoma of the vulva were compared with forty-five patients who underwent radical vulvectomy for similar lesions. Vulvar wound infection and breakdown were infrequent in both groups. Anal incontinence developed postoperatively in five of the modified radical vulvectomy patients and in none of the radical vulvectomy patients. Urinary incontinence developed postoperatively in two of the modified radical vulvectomy patients and in seven of the radical vulvectomy patients. Possible reasons for these differences are discussed. One invasive local recurrence (2.2%) developed in the modified radical vulvectomy group and two (4.4%) local recurrences developed in the radical vulvectomy group. A modified radical vulvectomy appears to be efficacious for the vulvar phase of treatment of localized invasive squamous cell carcinoma of the vulva.

Experience with the EndoPap device for the cytologic detection of uterine cancer and its precursors: a comparison of the EndoPap with fractional curettage or hysterectomy.

Cytologic assessment of the endometrium with the EndoPap sampler was compared with curettage or hysterectomy in 249 women with symptoms. The sensitivities for the detection of primary corpus cancer and hyperplasia were 0.90 (59/66) and 0.58 (18/31), respectively. All six cases of atypical endometrial hyperplasia were detected by the EndoPap device. Malignant EndoPap cytologic findings were present in 4 of 10 patients with a primary adnexal malignancy and normal endometrial histologic findings. Ninety-two percent of primary uterine cervical cancers were detected by EndoPap cytologic sampling. The specificity for the cytologic diagnosis of benign conditions was 0.93. EndoPap cytologic sampling has a reasonably high sensitivity for the detection of uterine cancers and preinvasive endometrial lesions with a high risk of progression to carcinoma. Further evaluation as to its usefulness in a screening program for uterine and adnexal cancers in postmenopausal women should be considered.

Giant Brenner tumor. Case report.

A case is reported of an unusually large benign cystic Brenner tumor. Larger solid tumors have been reported, and, additionally, proliferating Brenner tumors are most often large and cystic. However, the tumor described in this presentation appears to be the largest entirely cystic Brenner tumor reported to date.

Adenocarcinoma of the endometrium and endometrioid carcinoma of the ovary associated with pregnancy.

Nine well-accepted cases of endometrial carcinoma associated with pregnancy have been reported. A 10th patient is added and the cases are briefly summarized. At the time of her definitive surgery 6 weeks postpartum, our patient was also found to have a Stage I endometrioid ovarian carcinoma. Nine of the 10 cases have been well-differentiated adenocarcinoma or adenoacanthoma and the lesions have tended to be focal with minimal or no invasion. Given the small number of patients, conclusions regarding prognosis and treatment are difficult to make. However, in younger patients with noninvasive adenocarcinoma of the endometrium, the adnexa may be spared. Endometrioid adenocarcinoma of the ovary, discovered incidentally in our patient, is associated with a concomitant adenocarcinoma of the endometrium in 5-29% of cases, but the present case in which the lesions coexisted with pregnancy appears to be the first such report in the literature.

Carcinoma in situ of the vulva: 24 years' experience in southwest Florida.

We retrospectively studied 125 patients treated for carcinoma in situ of the vulva from 1961 through 1984, with follow-up ranging from one to 24 years. Patients' ages ranged from 24 to 90 years, with a mean age of 53 years. Multifocal disease was more common in women under age 40. Pruritus was the most common complaint, but 60% of the patients were asymptomatic. Twenty-five patients (20%) had other associated malignancies: carcinoma in situ of the cervix in ten patients, invasive carcinoma of the cervix in six, multifocal carcinoma in situ involving vulva, vagina, and cervix in five, vaginal carcinoma in situ in two, and endometrial carcinoma in two. Sixty-five patients were treated primarily with wide excision, 45 with total vulvectomy, seven with "subtotal" vulvectomy, three with skinning vulvectomy, and three with vulvectomy and bilateral groin node dissection; two patients refused treatment. Fifteen patients had a recurrence--recurrent carcinoma in situ in ten, and invasive carcinoma of the vulva in five. Whether the patient had had total vulvectomy or a lesser procedure appeared to make no difference in the recurrence rate. Thus a well planned excision of vulvar carcinoma in situ appears to be the treatment of choice. All recurrences were in patients over age 40, so although the lesion is histopathologically identical in the younger patients, its biologic behavior seems to be more benign. Since it is possible, however, that invasive disease will ultimately develop in some of the younger patients, careful follow-up is still required.

Basal cell carcinoma of the vulva with inguinal lymph node metastases.

Basal cell carcinoma of the vulva is a rare neoplasm which is generally thought to be indolent, locally invasive, and nonmetastasizing. A case of basal cell carcinoma of the vulva with metastases to the ipsilateral inguinal lymph nodes is presented. This is the third well-documented case in the literature of vulvar basal cell carcinoma with inguinal lymph node metastases.

Role of needle biopsy in the investigation of gynecologic malignancy.

Three methods were used to investigate and evaluate patients with primary and persistent/recurrent pelvic malignancy in the gynecologic oncology services at two medical centers. The 22-gauge Chiba needle was utilized with fluoroscopic guidance to perform fine needle aspiration (FNA) of pelvic and paraaortic lymph nodes that appeared abnormal on lymphangiography (LAG). The Tru-cut needle was used to obtain tissue samples from beneath the surface epithelium of the cervix, vaginal vault and parametrium. A disposable, hand-held syringe and 20-gauge needle were used to aspirate supraclavicular and inguinal lymph nodes and cul-de-sac nodules. One hundred thirty-eight patients were evaluated, with positive results in 66 (47.8%). Surgical exploration was used to further investigate 16 negative results that did not correlate with LAG and/or clinical presentation. The sensitivity and predictive value of a negative result for the three methods was Chiba needle FNA/LAG, 62.1% and 65.6%; Tru-cut needle biopsy, 94.4% and 93.5%; and hand-held syringe and needle, 87.5% and 66.7%, respectively. All three techniques proved to be safe, uncomplicated and rapid methods of assessing gynecologic tumor spread. Positive results from these techniques can often replace surgical exploration, with a considerable savings in patient morbidity and hospitalization, and permit additional treatment to proceed without delay. Negative results still require surgical validation.

Craniopharyngioma arising in the pharyngeal hypophysis.

Four cases of nasopharyngeal craniopharyngiomas have been previously reported in the medical literature. They were, in fact, only nasopharyngeal extensions of tumors originating in the anterior pituitary of the sella turcica. Pituitary adenomas can arise from any part of the craniopharyngeal canal. Supporting this theory are four reported cases of pituitary adenomas in the body of the sphenoid bone separate from both the sella turcica and the nasopharynx. The discovery by Erdheim in 1904 of the pharyngeal hypophysis located on the posterior edge of the vomerine bone raises the possibility of a tumor arising in this tissue. We report the case of a craniopharyngioma limited entirely to the nasopharynx and specifically to the posterior end of the vomer. We believe it to be the only reported example of a true neoplasm of the pharyngeal hypophysis first described by Erdheim.

Carcinoma of the endometrium.

PIP: Endometrial cancer is the cause of considerable morbidity among women, but the disease has been underrated and its management more casual than its virulence warrants. Endometrial carcinoma is the most frequently diagnosed invasive neoplasm of the female genital tract in the US, and is third in incidence after breast and colonic cancer. The white population of the US has the highest age standardized incidence of endometrial cancer in the world, India and Japan have the lowest, and the European countries occupy intermediate positions. Between 75% and 80% of women diagnosed with endometrial cancer are postmenopausal, and the mean age at diagnosis is about 60 years. In many cases endometrial hyperplasia is misdiagnosed as frank malignancy. The predisposing factors for endometrial cancer seem to be obesity, hypertension, diabetes mellitus or an abnormal glucose tolerance curve, and prolonged or unopposed estrogen stimulation. Raised estrogen levels may occur in the following situations: 1) women with functioning ovarian tumors that produce estrogen; 2) women with polycystic ovarian disease; 3) women with ovarian dysgensis (Turner's syndrome) managed with estrogen replacement therapy; 4) women taking high estrogen sequential oral contraceptives (OCs); and 5) women undergoing estrogen replacement therapy. There is an increased risk of endometrial carcinoma associated with nulliparity. Carcinoma of the endometrium occurs in a variety of subtypes, the most frequent being adenocarcinoma, followed by adenocanthoma, adenosquamous carcinoma, clear cell carcinoma, papillary adenocarcinoma, and secretory carcinoma. Overall 5-year survival rates are 72% for adenocarcinoma, 68% for adenocanthoma, and 26% for adenosquamous carcinoma. The true extent of endometrial cancer can be ascertained only after exploratory laparotomy and then various therapies may be used according to the stage of the disease.^ieng

Glandular intraepithelial neoplasia (GIN)--a unifying concept of the precursors of endometrial adenocarcinoma.

There is considerable variation and a good deal of confusion surrounding definitions and nomenclature for premalignant lesions of the endometrium. A unifying concept, based on the model of cervical intraepithelial neoplasia, is proposed to provide a uniform, practical basis for the diagnosis and management of the precursors of endometrial cancer. Lesions would be classified as glandular epithelial neoplasia (GIN) Grades, 1, 2 and 3. Illustrated examples, and comparisons with other classifications are provided.

Modern management of gestational trophoblastic disease.

Gestational trophoblastic disease is a disorder of pregnancy which may present in a very benign or malignant fashion. Hydatidiform mole complicates approximately 1 in 2000 pregnancies in the United States. The diagnosis may be made prior to evacuation if the signs and symptoms are kept in mind. When the patient presents with spontaneous expulsion of typical molar tissue, a complete evaluation is carried out, including physical examination, uterine curettage for histologic study, and initiation of weekly beta subunit of HCG determinations. At 8 weeks' post-evacuation, about 50% of patients continue to have detectable serum HCG levels. Of these patients, about half may develop chorioadenoma destruens (invasive mole) or choriocarcinoma and require chemotherapy (6, 16). Patient stratification in a clinical classification system based on anatomical extent of disease and certain risk factors is essential for proper management. Review of results obtained at gestational trophoblastic disease treatment centers has shown that with exception of the high-risk patient, virtually 100 per cent cure is possible with early diagnosis and appropriate treatment. Treatment of the high-risk patient with initial triple-drug chemotherapy and simultaneous irradiation of liver or brain metastases may be expected to yield a 90 per cent complete remission. If complete remission in the high-risk patient is maintained for 3 months after cessation of treatment, there appears to be a 98 per cent chance of remaining free of disease (47). The information accumulated in the 25 years since methotrexate was introduced into the treatment of gestational trophoblastic disease has made these excellent results possible. Aggressive multiagent chemotherapy, proper patient classification, radiation, surgery, and utilization of the beta subunit of HCG to monitor therapy are all pivotal in achieving these successes of modern management.