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Biomedical subjects

M J Merino

Publications and source records attributed to M J Merino.

At least 127 records · Page 7Linked to original sources
PubMed1991

Thyroid cancer: a lethal endocrine neoplasm.

This conference focuses on the controversies about managing thyroid cancer, emphasizing the possibility that the treatment of patients with potentially fatal thyroid cancer may be improved. Although the mortality rate from thyroid cancer is low, it is the highest among cancers affecting the endocrine glands (excluding the ovary). Exposure to radiation during childhood in the 1930s and 1940s increased the incidence of but not the mortality from thyroid cancer, because these tumors are mainly papillary cancers developing in young adults. These rates may change as the exposed cohort ages. Risk factors that increase mortality include older patient age and the growth characteristics of the tumor at diagnosis, the presence of distant metastases, and cell type (for example, the tall-cell variants of papillary cancer, follicular cancer [to be distinguished from the more benign follicular variant of papillary cancer], medullary cancer, and anaplastic cancer). Local metastases in lymph nodes do not seem to increase the risk for death from papillary cancer, but they do increase the risk for death from follicular and medullary cancer. In the latter, mortality is decreased by the early detection and treatment of patients with the familial multiple endocrine neoplasia syndrome 2a. There are excellent tumor markers for differentiated cancer of the parafollicular and of the follicular cells (serum calcitonin and serum thyroglobulin levels, respectively). Measuring the calcitonin level allows early diagnosis of familial medullary cancer, whereas measuring the thyroglobulin level, although useful only after total thyroidectomy, allows early recognition of recurrence or metastases of papillary or follicular cancer. Initial surgery, protocols for follow-up, and the use of radioiodine for the ablation of any residual thyroid and the treatment of metastatic cancer are discussed. Because these tumors resist currently available chemotherapy regimens, possible ways to increase the effectiveness of radioiodine therapy are considered as are new approaches to treatment.

Carcinoma↗
PubMed1991

Langerhans cell histiocytosis of the female genital tract.

Langerhans cell histiocytosis (LCH) of the female genital tract is rare. Four new cases are reported, and there is a review of the 38 cases in the literature. This disease may involve the vulva, vagina, cervix, endometrium, and ovary. Four distinct patient groups, segregated on the basis of initial presentation and subsequent anatomic extent of disease, were categorized as follows: (1) "pure" genital LCH, (2) genital LCH with subsequent multi-organ involvement, (3) oral or cutaneous LCH with subsequent genital and multi-organ involvement, and (4) diabetes insipidus with subsequent genital and multi-organ disease. Although involvement of the genital tract can occur at any age, it is most common in young adulthood. Clinically, LCH may mimic either primary neoplasia or various inflammatory lesions; the major pathologic differential diagnosis is venereal and other inflammatory diseases. The pure genital form may have a distinct nosologic position in the spectrum of LCH similar to the "pure," self-limited cutaneous histiocytosis seen in infants. There is no correlation between histologic findings and the outcome of the genital lesions. There is also no correlation between clinical presentation and/or the extent of involvement and outcome of genital lesions; complete regression, partial improvement, persistent lesions, and recurrences were seen in all four groups of patients. The treatment of genital LCH is not well defined and is highly individualized. Therapy has included surgery, radiation, topical corticosteroids, topical nitrogen mustard, systemic chemotherapy, and combination therapy; mixed results were obtained with all treatment modalities. Although no modality has been shown to yield a superior outcome, complete surgical excision is advocated as initial therapy.

Adult↗
PubMed1991

Molecular analysis of genetic changes in the origin and development of renal cell carcinoma.

Renal cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3 which suggests the presence of a tumor suppressor gene at this location. In order to more precisely define the location of the renal cell carcinoma gene and to differentiate molecular changes occurring in early stages of renal neoplasia versus those occurring later in malignant progression, DNA from normal and tumor tissue from 60 patients with various stages of renal cell carcinoma was analyzed for loss of alleles at different chromosomal loci. In tumor tissue from 51 of 58 evaluable patients (88%) there was loss of heterozygosity at one or more of 10 loci tested on chromosome 3 independently of tumor stage. Analysis of the genotypes identified the distal portion of 3p bounded by D3S2 and D3S22 (3p21-26) as the region of the disease gene. In tumor tissue from patients with advanced renal cell carcinoma, we found loss of heterozygosity on chromosome 11p in 5 of 21 (24%), on chromosome 13 in 3 of 9 (33%), and on chromosome 17 in 2 of 19 (11%). We found no loss of heterozygosity at the loci on chromosomes 11, 13, or 17 in tumor tissue from patients with localized renal cell carcinoma (N = 5). These data suggest the existence of a tumor suppressor gene on chromosome 3p which may be essential to the genesis of sporadic renal cell carcinoma and that other tumor suppressor genes are associated with progression of this malignancy.

Adult↗
PubMed1991

Level of axillary involvement by lymph node metastases from breast cancer is not an independent predictor of survival.

We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Positive gallium-67 citrate scintigraphy in Wiskott-Aldrich syndrome with malignant lymphoma.

This case describes the first detection of solid lymphoma lesions by gallium-67 scintigraphy in a 12-year-old patient with Wiskott-Aldrich syndrome. Gallium 67 uptake was found in multiple sites in the patient who had developed an undifferentiated small, non-cleaved cell lymphoma. Response to chemotherapeutic treatment is correlated with findings on the gallium scintigraphy follow-up.

Child↗
PubMed1991

Value of gross cystic disease fluid protein-15 in distinguishing metastatic breast carcinomas among poorly differentiated neoplasms involving the ovary.

Women with breast cancer have an increased risk of developing primary ovarian tumors. Because a differential diagnosis between primary and metastatic tumors may be difficult in poorly differentiated ovarian neoplasms, breast carcinoma markers may be helpful in establishing the primary site of origin. Gross cystic disease fluid protein-15 (GCDFP-15), a well-known marker of apocrine differentiation, has been reported as a highly specific and sensitive breast carcinoma marker. To evaluate the usefulness of GCDFP-15 as a marker for metastatic breast cancer, we have studied, by the avidin-biotin-peroxidase technique, 14 cases of breast cancer metastatic to the ovary and compared them with 32 primary ovarian tumors and seven cases of ovarian metastases other than breast in origin. Two cases of primary ovarian cancer metastatic to the breast were also included. A strong cytoplasmic immunostaining was found in 10 of 14 cases (71%) of ovarian metastasis from breast carcinoma, and in most cases a characteristic paranuclear staining was noted. All primary ovarian tumors were negative. Ovarian metastases from tumors other than breast and both cases of ovarian carcinoma metastatic to the breast were negative. These results are highly significant (P less than .00001) and demonstrate the value of GCDFP-15 in establishing a primary breast origin among neoplasms of unknown origin involving the ovaries.

Antibodies, Monoclonal↗
PubMed1991

Monoclonal antibodies for radioimmunoscintigraphy of breast cancer.

Breast cancer is the leading cause of cancer deaths among females, and it is estimated that each year, one in ten American women will be newly diagnosed as having the disease. It is therefore not surprising, that a great deal of effort has been made to better understand the biology of breast cancer, and that investigators keep up the search for new tools to better characterize, diagnose and treat these tumours. In this regard, the introduction of the hybridoma technique in 1975 by Kohler and Milstein has lead to an extensive work in the characterization of monoclonal and polyclonal antibodies against breast cancers. A large number of antibodies has been raised to different epitopes present in normal and neoplastic breast tissue; but unfortunately we have yet to find a highly sensitive and specific monoclonal antibody for breast cancer that can successfully be used for scintigraphic detection of nodal metastases and for radioimmunotherapy treatment of this disease. As possible radioimmunodiagnostics, antibodies are known which react with the following antigens: (1) cytoskeletal proteins (2) breast cell products (3) steroid receptors (4) putative tumor-associated antigens (5) oncogene products (6) pregnancy-related products (7) basement membrane antigens (8) degradative enzymes (9) cell receptors for extracellular matrix molecules (10) multidrug resistance gene product (p-glycoprotein) (11) proliferative markers.

Antibodies, Monoclonal↗
PubMed1991

Vaginal cancer: the role of infectious and environmental factors.

Primary cancers of the vagina are rare. They comprise 1% to 2% of all gynecologic malignancies and occur predominantly in older women. The diagnosis of primary carcinoma of the vagina requires that the cervix and vulva be intact and that no clinical evidence of other primary tumors exist. Approximately 90% of all vaginal tumors are squamous cell in type on histologic examination. Adenocarcinoma, which is much less common (2% to 4%), is seen primarily in younger women with in utero exposure to diethylstilbestrol. In addition to exposure to diethylstilbestrol, other environmental factors have been associated with the development of vaginal tumors, including chronic irritation from pessaries, previous hysterectomy for benign disease, immunosuppression therapy, cervical irradiation, and endometriosis. Infectious causes seem to play an even more pernicious role in vaginal cancer. The two agents most often implicated are herpes simplex virus and human papillomavirus. These viruses appear to serve as cofactors in the inducement of various genital cancers, working together or with environmental agents such as diethylstilbestrol and host-related genetic abnormalities. The prognosis of vaginal cancer depends on the stage of the disease, with an overall 5-year survival rate of 80% to 90% for early stages.

Adenocarcinoma↗
PubMed1991

Immunohistochemical detection of P-glycoprotein in endometrial adenocarcinoma.

P-glycoprotein (Pgp) has emerged as the central mediator in classic multidrug resistance in model systems in vitro. High levels of Pgp also have been detected in many normal human tissues and tumors; and its role in clinical drug resistance is currently under investigation. Recently significant levels of Pgp were localized to gravid and secretory endometrium; and it was demonstrated that the combination of estrogen and progesterone is sufficient to induce high levels of both Pgp mRNA and Pgp in uterine secretory epithelium. These findings suggest that increased Pgp expression also may be present in hormone-responsive malignancies such as endometrial adenocarcinoma. To determine whether Pgp is expressed in endometrial adenocarcinoma, 36 endometrial adenocarcinomas (grade I [n = 17]; grade II [n = 6]; grade III [n = 13]) were investigated retrospectively by the avidin-biotin-complex immunohistochemical procedure using three murine monoclonal antibodies (MAb) MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Seventy-two percent of the tumors showed positive immunostaining with at least one MAb; 67% showed immunostaining with MAb C219, 50% with MAb C494, and 62% with MAb JSB-1. Forty-six percent of tumors were immunoreactive to two and 29% to all three antibodies. Membranous and Golgi/paranuclear type staining patterns were observed. Overall the intensity of immunostaining varied from one sample to another for a given tumor type, and considerable heterogeneity of expression was commonly seen within a given tumor. Strong to moderate immunoreactivity was seen in diffusely infiltrating, adenosquamous, and serous papillary carcinomas. In general, immunoreactivity to MAb C494 was weaker than MAb C219 or MAb JSB-1. Adenomatous and non-neoplastic endometrium adjacent to the tumors displayed strong membranous immunostaining with MAb JSB-1. Endometrial capillaries showed weak-to-moderate immunostaining to all three antibodies. It is concluded that Pgp is commonly expressed in endometrial adenocarcinoma and may be a significant factor responsible for their drug-resistant nature subject to modulation by progesterone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

P-glycoprotein expression is increased in human secretory and gestational endometrium.

To determine the expression, distribution, and intracellular localization of the multi-drug resistance gene product P-glycoprotein (Pgp) in the human menstrual cycle and in early gestational endometrium, we retrospectively studied 36 endometrial samples utilizing 3 murine monoclonal antibodies (MAbs), MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Formalin-fixed, paraffin-embedded endometrial samples obtained from 36 women of reproductive age with normal menstrual cycles were assigned morphologic menstrual dates: proliferative (N = 10), secretory (N = 19), menstrual (N = 1), and gestational endometrium (N = 6). The cellular localization, staining intensity, and percentage of Pgp immunoreactive cells varied with the phase of the menstrual cycle. Early proliferative endometria revealed no Pgp immunoreactivity for all three MAbs. Mid-proliferative endometria showed weak immunostaining in less than 15% of the glandular epithelia. Late proliferative endometria showed a strong apical paranuclear/Golgi staining pattern. Early secretory endometria showed strong luminal membranous, subnuclear vacuolar membranous, and supranuclear vacuolar membranous immunostaining to all 3 MAbs in greater than 80% of the glandular epithelia. Apical paranuclear/Golgi and membranous staining were present in nonvacuolated mid-secretory glands. Immunoreactivity diminished in the late secretory phase with mild to moderate staining in less than 35% of the endometrial glands. Menstrual endometria showed weak, focal staining. All gestational endometria showed marked cytoplasmic, membranous, and apical/Golgi immunostaining both in the hypersecretory (Arias-Stella) endometrial glands as well as in the decidua. In general, the intensity of MAb C494 immunostaining was weaker than that of MAb C219 or JSB-1. These results suggest the following: Pgp expression parallels that of nuclear progesterone receptor expression in the normal human endometrial cycle and early gestational endometrium; Pgp expression corresponds to rising plasma and tissue levels of progesterone as well as to morphologic changes in the endometrial glandular epithelium associated with the marked development of the secretory apparatus; Pgp expression is hormonally regulated and may be involved in uteroplacental transport of substrates important in the implantation process and in early embryo-endometrial interactions; and Pgp may be involved in the transport of progesterone across the uterine epithelium during pregnancy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Papillary endothelial hyperplasia in the thyroid following fine-needle aspiration.

A 74-year-old woman was found to have exuberant papillary endothelial hyperplasia within her thyroid gland subsequent to multiple fine-needle aspiration biopsies of a Hürthle cell neoplasm. To our knowledge, this histologic alteration in the thyroid has not been previously reported. We describe this unusual complication following fine-needle aspiration, and we delineate the clinicopathologic and differential diagnostic features.

Adenoma↗
PubMed1990

Parathyroid imaging by Tc/Tl scintigraphy.

Between 1983 and 1988, a total of 224 99mTc/201Tl subtraction parathyroid scintigraphy studies were performed in 214 patients (136 women, 78 men, average age 50, +/- 15 years) with clinical and biochemical signs of hyperparathyroidism. Of the 214 patients, 113 underwent surgical exploration, and 127 benign parathyroid lesions were found, 48 of which were correctly localized by scintigraphy (sensitivity 38%). We detected 30 of 71 adenomas (42%) and 18 of 56 hyperplastic glands (32%). Additionally, the scans localized 2 of 6 parathyroid carcinomas in 5 patients. Overall, 83 parathyroid lesions were missed. There was no significant difference in size between detected and missed lesions. Previous neck surgery (65 of 113 patients) was not a significant detriment to scan sensitivity; but correct detection did depend upon the anatomic site of the lesion: 39% (n = 109) were detected in the typical site, 44% (n = 9) intrathyroidal, and 11% (n = 9) in the anterior and/or superior mediastinum. In conclusion, these results show only limited value for this 99mTc/201Tl subtraction scintigraphy protocol as the initial procedure for localization of abnormal parathyroid tissue prior to surgical exploration.

Female↗
PubMed1990

Scintigraphic findings and follow up in Erdheim-Chester disease.

Two cases of Erdheim-Chester disease are presented: a 26-year-old white male patient with lipoidgranulomatosis of numerous long and flat bones and infiltration of pericardium, pleura, liver, spleen, thyroid, skin, conjunctiva, gingiva, and false vocal cord; and a 54-year-old white male with involvement of bones, orbits, brain, pericardium, and retroperitoneum. The scintigraphic findings in this disease are described, and a comprehensive review of the 27 previously reported cases is given including an assessment of the value of scintigraphy for diagnosis and follow up of this rare disease.

Adult↗
PubMed1990

The effects of hormonal and chemotherapy on tumoral and nonneoplastic breast tissue.

One hundred four sequential pretherapy and posttherapy breast tissue specimens from 57 patients with locally advanced and metastatic breast cancer were evaluated in an attempt to define the effects of systemic chemotherapeutic agents on the tumors and residual nonneoplastic breast tissue. The patients were treated uniformly at the National Cancer Institute on an experimental protocol combining systemic chemotherapy with attempted hormonal synchronization. Tumors were sampled prior to and following several cycles of chemotherapy to a maximum objective clinical response (average number of cycles, 7). In 38 cases, the posttreatment biopsy was positive for tumor. The most striking histologic change was extreme vacuolization of tumor cells that often resembled histiocytes. Atrophy of the terminal duct lobular unit (TDLU) and atypia of epithelial cells in TDLU and large ducts were also seen. Severe degrees of epithelial atypia occasionally proved to be difficult to distinguish from residual intraductal carcinoma. Breast biopsies were stained with antibodies to cytokeratin, epithelial membrane antigen (EMA), B72.3, lactalbumin, and SP1 using immunoperoxidase techniques. The number of cases showing immunoreactivity with antibodies to cytokeratin, EMA, and B72.3 remained approximately the same before and after therapy, while SP1 expression decreased and lactalbumin expression increased after therapy. Recognition of chemotherapeutic changes in breast tissue is important since systemic chemotherapy plays an important role in the management of breast cancer.

Adenocarcinoma, Mucinous↗
PubMed1990

Collecting duct carcinoma of the kidney.

Collecting duct carcinoma is an unusual variant of renal cell carcinoma, whose appearance and behavior are not well established. We identified six cases of collecting duct carcinoma in our files. The clinical, pathologic, and immunohistochemical characteristics of these tumors are reported. The most common symptom was gross hematuria (four cases). Two patients had cervical adenopathy due to metastatic tumor. Four rapidly developed systemic metastases and died within 4 to 24 months. The primary renal tumors were located predominantly in the renal medulla and pelvis and had a partially cystic white-gray appearance. Histologic examination showed prominent tubulopapillary structures, nests of clear cells, and infiltrating tubules in a dense desmoplastic stroma. Atypical hyperplastic changes were found in some of the adjacent collecting ducts. Mucicarminophilic material was present in glandular elements in all six cases. Immunohistochemical studies revealed positivity with antibodies to epithelial membrane antigen, keratins, peanut agglutinin, vimentin, Leu M1 and lysozyme. The location of this tumor in the medulla, its distinctive histologic appearance, mucin positivity, expression of high molecular weight cytokeratins, and peanut agglutinin suggest that this is a distinct clinicopathologic entity which has an aggressive clinical course.

Adult↗
PubMed1990

Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue.

Production of type IV collagenase by tumor cells has been linked to their metastatic potential in several experimental models. A possible role for this enzyme in basement membrane type IV collagen turnover has also been suggested. Two recently developed affinity-purified, monospecific antibodies directed against the amino terminus (H1), or an internal active site domain (metal binding region [MBR]) of human type IV collagenase, were employed in the avidin-biotin-immunoperoxidase technique in formalin-fixed, paraffin-embedded breast tissue samples from 55 patients. Intense cytoplasmic immunostaining of myoepithelial cells was found in normal and hyperplastic tissue, and discontinuous staining was noted in intraductal carcinomas. Luminal epithelial cells were negative or weakly positive in large- or medium-sized ducts but reacted frequently in normal terminal ducts and hyperplastic lesions. Epithelial cells in intraductal carcinomas exhibited immunoreactivity in 20 of 23 cases. Invasive carcinomas were positive in 36 of 40 cases, and metastatic cells in lymph nodes stained in 10 of 12 cases. These results support a role for type IV collagenase in the basement membrane remodeling of normal breast. Our findings suggest that myoepithelial cells play a pivotal role in this enzymatic activity. The high percentage of positive cells in invasive carcinomas and the strong immunoreactivity of lymph node metastases support the role of the enzyme in tumor invasion and metastasis and suggest that tumor cells are the essential source of the enzyme in these processes.

Antibodies↗
PubMed1990

Renal oncocytoma with cylindromatous changes: pathologic features and histogenetic significance.

We describe two cases of renal oncocytoma which showed an unusual light microscopic appearance characterized by nests of cells containing collections of eosinophilic hyaline material around and within oncocytic epithelial cell nests. Electron microscopy of the hyaline material showed a partly amorphous and partly lamellated structure, and immunohistochemistry for type IV collagen was positive. These cylindromatous changes are similar to the "glashelle Zylinder" of Billroth (Billroth T: Beobachtungen über geschwülste der speicheldrüsen. Virchous Arch [Pathol Anat] 17:357, 1859) described in adenoid cystic carcinoma and are most likely the result of an accumulation of basement membrane material in invaginations projecting into the surface of the basal plasmalemma. Since such invaginations occur in the normal distal tubule, our cases support origin of renal oncocytoma from distal tubular epithelial cells.

Adenoma↗