Biomedical subjects

S E Mills

Publications and source records attributed to S E Mills.

At least 19 recordsLinked to original sources

PubMed1992

Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma.

The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.

Adrenal Cortex Neoplasms↗

PubMed1992

Lobular capillary hemangioma. An immunohistochemical study including steroid hormone receptor status.

Twenty-one lobular capillary hemangiomas (LCH), including lesions from six pregnant patients, were examined by immunohistochemical analysis. Antibodies to estrogen and progesterone receptor proteins were used to determine whether these steroid hormones play a direct role in LCH development and growth. All 21 LCHs were negative for both receptor proteins. Contrary to the association of LCH with pregnancy and oral contraceptive use, the absence of these steroid receptors strongly suggests that estrogen or progesterone are not directly involved in the formation of these lesions. All 21 LCHs were stained with Ulex europaeus lectin and with a panel of antibodies directed against cytokeratin, vimentin, Factor VIII, collagen Type IV, and muscle-specific actin. Endothelial cells in LCH, both in cellular proliferations with poorly formed lumens and in well-formed capillaries, were labeled by Factor VIII, Ulex europaeus lectin, and vimentin. A population of concentrically arranged, perivascular spindle-shaped cells was highlighted by positive staining for muscle-specific actin, collagen Type IV, and vimentin. The spindled cells were associated with both well-developed and immature vessels in all lesions. The appearance, immunophenotype, and location of these cells is consistent with a pericytic origin. Although the intimate association of both endothelial cells and pericytes suggests a reactive, as opposed to neoplastic, origin, other benign vascular tumors traditionally considered neoplastic have a similar bicellular composition. Accordingly, the findings neither support nor refute a neoplastic origin for LCH.

Adolescent↗

PubMed1992

Immunoreactivity for BER-EP4 in adenocarcinomas, adenomatoid tumors, and malignant mesotheliomas.

Ber-EP4 is a recently characterized monoclonal antibody directed against a cell surface glycoprotein that is putatively present on human epithelial cells but lacking on the mesothelium. To investigate the diagnostic efficacy of Ber-EP4 in distinguishing adenocarcinoma from mesothelioma, we studied formalin-fixed, paraffin-embedded sections from well-documented cases of adenocarcinoma (120 cases), adenomatoid tumor (nine cases), and malignant mesothelioma (49 cases). Of the 120 adenocarcinomas, 103 (86%) showed membranous Ber-EP4 positivity, with diffuse reactivity noted in 82 cases and focal staining in 21 cases. Reactivity with Ber-EP4 was also observed in two of nine adenomatoid tumors (22%) and 10 of 49 mesotheliomas (20%). Staining in the mesotheliomas was restricted to epithelioid areas and generally focal. In one mesothelioma, however, Ber-EP4 stained the majority of neoplastic cells. In contrast to previous reports, we conclude that positivity with Ber-EP4 does not exclude the diagnosis of mesothelioma. Nonetheless, most Ber-EP4-positive mesotheliomas exhibit only focal positivity, as opposed to the extensive staining commonly observed in adenocarcinomas. Ber-EP4 has diagnostic utility in the discrimination of mesothelioma from adenocarcinoma, but it is best utilized in an antibody panel that includes other markers of carcinomatous differentiation.

Adenocarcinoma↗

PubMed1992

Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and immunohistochemical study of 40 cases.

In this study of 40 cases of basaloid squamous cell carcinoma, 83% arose in the pyriform sinus, base of tongue, tonsil, and larynx. The 35 men and five women ranged in age from 27 to 88 years (median 62). In patients for whom social habits were recorded, 24 of 26 patients were smokers and 22 of 25 drank ethanol. Most presented with stage III or IV disease. Twenty-seven patients had regional metastases at the time of presentation and 15 developed distant metastases. Seventeen patients died with disease (median survival 18 months). The tumors were composed of moderately pleomorphic basaloid cells forming nests, cords, and frequent cribriform patterns. Squamous dysplasia of surface mucosa, focal squamous differentiation within invasive basaloid squamous cell carcinoma, or foci of conventional squamous cell carcinoma were present, alone or in combination. All studied neoplasms were immunohistochemically positive for keratins with the 34 beta E12 antibody. Approximately 80% were immunoreactive using AE1/AE3 or CAM 5.2. Epithelial membrane antigen, carcinoembryonic antigen, and S100 protein were found in 83%, 53%, and 39%, respectively, of the cases. Diffuse, weak immunoreactivity for neuron-specific enolase was seen in 75% of tumors. Synaptophysin, chromogranin, muscle-specific actin, and glial fibrillary acidic protein were absent. Basaloid squamous cell carcinoma has been confused with adenoid cystic carcinoma and small cell undifferentiated carcinoma, but is usually distinguishable in routine hematoxylin and eosin-stained sections, or, in rare problematic cases, with the aid of immunohistochemical studies. Distinction is warranted because the biologic behavior of basaloid squamous cell carcinoma differs from that of both of these lesions.

Adult↗

PubMed1992

Intraarticular synovial sarcoma.

A 43-year-old man presented with decreased range of motion in his left knee and a painful medial joint mass that was grossly visible. Arthroscopy demonstrated a mobile, flat mass 3 cm in diameter in the knee joint that seemed to be loosely tethered to the synovium. The mass was excised, and light microscopic examination demonstrated a biphasic synovial sarcoma. There was no transition with the attached normal synovium. Immunohistochemically, the epithelial component was intensely positive for epithelial membrane antigen and cytokeratins (CAM 5.2 and AE 1/AE 3), and the spindle cell component was focally positive for these markers. The patient has no evidence of disease 9 years after only local excision. Although the term synovial sarcoma suggests a relationship to normal synovium, only rarely has truly intraarticular disease been reported.

Adult↗

PubMed1992

Estrogen inhibits calbindin-D28k expression in mouse uterus.

The cellular localization and hormonal controls of calbindin-D9k expression in the rodent reproductive tract have suggested new functions for this protein. The present studies were undertaken to extend the earlier studies of calbindin-D9k to the related protein, calbindin-D28k. Immunohistochemical studies revealed that calbindin-D28k was absent from female rat reproductive tissues, but was abundantly expressed in immature mouse uterus and oviduct. Immunoreactivity was restricted to the endometrial and glandular epithelium of the uterus and the oviductal epithelium. Neither 1,25-dihydroxyvitamin D- nor strontium-containing diets (to blunt 1,25-dihydroxyvitamin D production) affected expression of calbindin-D28k. Uterine, but not oviductal, calbindin-D28k decreased markedly at sexual maturity; this pattern persisted in pregnant mice and was reproduced in immature mice by the administration of estradiol (3 micrograms/day for 3 days). RNA extraction and Northern analyses demonstrated that estrogen markedly decreased calbindin-D28k mRNA abundance in the uterus, but not in the oviduct. These findings suggest that estrogen affects mammalian calbindin-D28k expression and represent a rare example of estrogen-induced down-regulation of gene expression.

Animals↗

PubMed1991

Denervation of transplanted porcine lung causes airway obstruction.

Lung transplantation can be complicated by a form of small airway obstruction known as bronchiolitis obliterans. We tested the hypothesis that lung denervation causes small airway obstruction in young pigs (10 +/- 1 weeks). Control pigs had an innervated native lobe, and study pigs had either a denervated native lobe or a denervated transplant lobe. Transplanted pigs received standard immunosuppression. At 10 weeks we measured isolated left lobe pulmonary mechanics. Dynamic resistance in both study groups was significantly higher than in the lobectomy group, whereas dynamic compliance in both study groups was significantly lower than in the lobectomy group. No significant difference in resistance or compliance was noted between the transplant and reimplant groups. Histologic changes consistent with rejection were noted in the transplant lobes. We conclude that the small airway obstruction noted in this model is due to operative denervation rather than to immunosuppression or rejection.

Animals↗

PubMed1991

Injury to the pre-pubertal vas deferens. I. Histological analysis of pre-pubertal human vas.

There is very little information in the literature on the development of the human vas deferens. Therefore, the age at which the pre- or para-pubertal vas deferens becomes large enough for a vasovasostomy to be technically feasible is unknown. To determine the age or degree of sexual maturity at which a microscopic vasovasostomy is technically feasible, we collected surgical or autopsy vasa from 34 young males over a three year period, and correlated vasal size to age and Tanner stage (degree of sexual maturity ranging from 1-childhood to 5-adult). The specimens were embedded and sectioned transversely in glycol methacrylate. Using image analysis, the total transverse area and diameter, and luminal area and diameter was determined for each specimen. Surprisingly, there was no change in vasal size from birth up through 11 years. From age 15 years and on, the vas was adult in size. The vas develops to adult size between Tanner stages 2 and 3. The average external and luminal diameters of pre-midpuberty specimens (Tanner stages 1 and 2) were 1.0 and 0.19 (mm.) and the diameters of post-midpuberty specimens were 2.1 and 0.43 (mm.), respectively. These results suggest that, in the event of a recognized iatrogenic injury to the vas deferens after midpuberty, a repair by a traditional microsurgical vasovasostomy is possible. If the vas is injured before midpuberty it may be technically difficult to repair by traditional microsurgical methods.

Adolescent↗

PubMed1991

Injury to the pre-pubertal vas deferens. II. Experimental repair.

We have previously shown that the human vas deferens does not change in cross-sectional size between birth and the middle of puberty. This suggests that if the human vas is injured prior to mid-puberty, repair by a traditional microsurgical vasovasostomy may be technically difficult. We propose that a chromic stent can be used to assist in the repair of vas injured before mid-puberty. This hypothesis was tested in Sprague-Dawley rats. At three weeks of age, male offspring were divided into three groups (eight to nine rats/group): 1) Sham group--a sham operation at three weeks, 2) VV group--bilateral transection of vasa at three weeks followed by a delayed repair at eight weeks by microsurgical vasovasostomy without a stent, 3) Stent group--bilateral transection of vasa at three weeks followed by immediate repair by aligning the lumens with a 6-0 chromic intravasal stent (suture) and holding the transected ends together with several seromuscular sutures. At four months all rats were fertility tested and a score was given to each rat (mean number of concepti among three females for each male rat). Analysis of anastomotic patency by flow rates and histology was performed. There was no statistical difference in the mean fertility score of 6.85 in the Stent group compared to 7.83 in the Sham group. However, a fertility score of 0.71 in the VV group was significantly decreased compared to the Stent and Sham group (p = .0003), despite no statistical difference between the groups in patency. This suggests that a recognized injury to the pre-pubertal human vas should be immediately repaired and the repair can be done using 6-0 chromic suture as an intravasal stent to help align the lumina of the smaller pre-pubertal vas.

Animals↗

PubMed1991

Malignant peritoneal mesothelioma in childhood with long-term survival.

A diffuse, well-differentiated, malignant peritoneal mesothelioma (MPM) developed in a nine-year-old girl. She received limited chemotherapy and radiation therapy and is alive and well without clinical evidence of disease 109 months after diagnosis. The neoplastic cells stained immunohistochemically for cytokeratin and epithelial membrane antigen but were unreactive with B72.3, anti-carcinoembryonic antigen, and anti-Leu-M1. Ultrastructurally, the tumor cells had abundant desmosomes, numerous tonofilament bundles, and variable-length microvilli. These findings confirm the mesothelial nature of the cells. Features consistent with malignancy included DNA aneuploidy by flow cytometric analysis and diffuse peritoneal involvement. The three previously described survivors with MPM were also premenarchal girls. Some MPMs in premenarchal girls have an indolent biologic behavior similar to that of low-grade peritoneal serous neoplasia or well-differentiated papillary mesothelioma in adult women.

Adolescent↗

PubMed1991

Sinonasal malignant melanoma. A clinicopathologic and immunohistochemical study of 14 cases.

The clinical, light microscopic, and immunohistochemical features of 14 sinonasal malignant melanomas were studied to show their diverse morphologic appearance and distinction from therapeutically more amenable neoplasms that occur in this region. The tumors arose in 6 men and 8 women (median age, 70 years). Eleven patients died of disease 7 to 44 months (median, 18 months) after diagnosis. The absolute median survival time was 18.5 months (range, 7 to 44 months). The predominant microscopic appearance was categorized as small blue cell in eight cases, spindle cell in three cases, epithelioid in two cases, and pleomorphic in one case. Eight tumors had multiple patterns. Five sinonasal malignant melanomas had theque-like growth, five had junctional change, and 10 contained at least rare melanin pigment. Fourteen, 13, and 12 sinonasal malignant melanomas were immunoreactive with anti-vimentin, HMB45, and anti-S100 protein antibodies, respectively. One epithelioid tumor positive for vimentin, S100, and HMB45 also contained scattered epithelial membrane antigen-positive and cytokeratin-positive cells, which emphasizes the need for a battery of stains to distinguish sinonasal malignant melanoma from carcinoma. All tumors were negative for leukocyte common antigen, muscle-specific actin, and synaptophysin. Diffuse immunopositivity for vimentin, S100 protein, and HMB45 allows distinction of sinonasal malignant melanomas from histologically similar neoplasms.

Aged↗

PubMed1991

The mystique of the mistake. With proposed standards for validating proficiency tests in anatomic pathology.

Variability in classification in anatomic pathology does not necessarily indicate that a mistake has been made. It is usually an artifact, created when pathologists choose a single category from among two or more justifiable alternatives. This is most common when standard classifications with uniform terminology are not used. It also can occur when classification systems are not constructed so as to insure mutual exclusivity of categories. It is proposed that a proficiency test in anatomic pathology should not be considered scientifically valid until a professional organization primarily concerned with anatomic pathology has endorsed its proposed classification system as having categories that are close to 100% mutually exclusive in the hands of expert pathologists not involved in developing the system. All possible precautions should be taken to insure that the "right answers" for any proficiency test are generated in a way that excludes the possibility of multiple justifiable alternatives.

Clinical Competence↗

PubMed1991

Interaction of somatotropin and genotype on the requirement for energy in two lines of finishing pigs.

Eighty barrows were used in a 2 x 2 x 4 factorial experiment to examine the effects of genetic line (Hampshire x Yorkshire, H x Y, and Yorkshire x Landrace, Y x L), somatotropin (dose, 0 and 5 mg/d) and energy intake (ad libitum, 93%, 86% and 80%) on growth performance and energy requirements for lean gain over the finishing phase of growth. Four diets were formulated to maintain equal intakes of protein, vitamins and minerals at different energy intakes. Somatotropin increased growth rate 30 to 35% across diets despite an 8 to 12% reduction in ad libitum feed intake. Lean growth rate (kg/d) was increased preferentially by ST in the faster-growing H x Y barrows, which showed a 2.8-fold greater maximum rate increase than the slower-growing Y x L barrows. In control barrows, 10% reductions in energy intake had no effect on lean gain and improved feed/lean gain about 10%. In somatotropin-treated barrows, lean gain was reduced with each energy restriction in H x Y; energy intake had no effect on lean gain in Y x L barrows. Feed/lean gain was improved 22% in Y x L barrows at the lowest energy intake. Data indicate that somatotropin accentuates breed differences in lean gain and energy requirements. Pigs with low lean-growth potential will benefit from restricted feeding, whereas strategies to increase energy intake in pigs with high lean-growth potential may be desirable.

Animal Feed↗

PubMed1991

Small-cell neuroendocrine carcinoma of the cervix. A human papillomavirus type 18-associated cancer.

Small-cell undifferentiated carcinomas comprise a rare but aggressive subset of uterine cervical neoplasms. Analogous to small-cell anaplastic carcinoma of the lung, these tumors frequently exhibit neuroendocrine differentiation. Although human papillomaviruses (HPV) types 16 and 18 are strongly associated with the development of cervical squamous carcinoma, there is as yet little information describing the relationship of these viruses to small-cell carcinomas. To address this question, we analyzed 20 cases of small-cell carcinoma of the cervix using in situ hybridization to detect HPV gene expression. In addition, immunohistochemistry was used to evaluate three markers of neuroendocrine differentiation. Eighteen of 20 tumors (90%) demonstrated some evidence of neuroendocrine differentiation; 17 of 20 (85%) expressed HPV type 16 or 18 messenger RNA. Of the neuroendocrine-positive cases, 14 of 18 expressed HPV 18 messenger RNA. In contrast, both of the cases with squamous differentiation were HPV 16 positive. These findings broaden the spectrum of HPV-associated cervical neoplasia and strongly suggest that HPV 18 is a viral type specifically associated with cervical small-cell neuroendocrine carcinomas.

Carcinoma, Small Cell↗

PubMed1991

Histologic classification of sinonasal intestinal-type adenocarcinoma.

Kleinsasser and Schroeder recently described a histologic classification system for woodworker-associated, intestinal-type adenocarcinomas of the sinonasal region. To determine if their approach is easily applied and prognostically meaningful for both woodworker-associated and sporadic intestinal-type adenocarcinomas in the sinonasal region, we analyzed 15 such cases. The 12 men and three women ranged in age from 37 to 75 years. Only four were woodworkers. All tumors arose in the nasal cavity or paranasal sinuses. The three authors independently classified the tumors with unanimous agreement in 11 (73%) of 15 cases. Disagreements were resolved by group review and consensus. Ten tumors were papillary tubular cylinder cell type; these were subdivided into grades I (four cases) and II (six cases) on the basis of cytologic atypia. Three tumors were alveolar goblet cell type; one tumor was signet-ring type; and one had a mixed pattern. Median survivals were papillary tubular I, 9 years; papillary tubular II, 3 years; and alveolar goblet cell, 7 years. It is concluded that this classification system is easy to apply, reproducible, and appears to identify a group of sinonasal intestinal-type adenocarcinomas (papillary tubular I) with a prolonged survival.

Adenocarcinoma↗

PubMed1991

Uterine intravascular menstrual endometrium simulating malignancy.

Intravascular menstrual endometrium, a rare finding in hysterectomy specimens, can pose clinically critical differential diagnostic problems. We describe a 28-year-old female with cervical dysplasia and numerous foci of menstrual endometrium in the parametrial blood vessels of her subsequent hysterectomy specimen. Histologically, the intravascular tissue consisted of small spindled stromal cells, larger cuboidal epithelial cells, or both components in close association. Immunohistochemically, the small spindled cells were vimentin positive and the larger cuboidal cells stained with epithelial markers. Distinction of intravascular menstrual endometrium from intravascular malignancies such as carcinoma, sarcoma, or lymphoma may be difficult, especially at the time of frozen-section diagnosis. Awareness of this process, attention to its cytologically bland, usually biphasic appearance, knowledge of the menstrual status, and application of appropriate immunohistochemical markers will allow distinction from neoplasia.

Adult↗

PubMed1991

Clear cell tumor of the lung. Immunohistochemical and ultrastructural evidence of melanogenesis.

Clear cell tumors of the lung (CCTL) are rare neoplasms of uncertain differentiation. A previous study of eight CCTL demonstrated a lack of epithelial features, but their exact nature remained unknown. In the current study of nine CCTL, immunohistochemistry using preliminary enzymatic digestion showed strong reactivity with the antimelanocytic markers HMB-45 (seven cases) and HMB-50 (six cases) and focal positivity for S-100 (nine cases), neuron-specific enolase (three cases), synaptophysin (one case), and Leu-7 (one case). Staining for cytokeratin, epithelial membrane antigen, chromogranin, and glial fibrillary acid protein was uniformly negative. Frozen-section immunoreactivity for vimentin and the antimelanocytic monoclonal preparation NKI/BETEB was noted in the one CCTL for which snap-frozen tissue was available. Ultrastructural examination of three glutaraldehyde-fixed CCTL showed rare neoplastic cells containing the full spectrum of melanosomes in two, one of which also contained neurosecretory-type granules. Aberrant melanosomal forms were identified in the third case. Melanosomes were not identified in the remaining five CCTL studied from formalin- or paraffin-retrieved material. The findings indicate that CCTL exhibits melanocytic differentiation. This feature may be of considerable value in distinguishing CCTL from other clear cell neoplasms.

Antibodies, Monoclonal↗

PubMed1991

Immunoreactivity for estrogen receptor protein in sweat gland tumors.

The histologic and immunophenotypic similarities between sweat gland carcinoma and breast cancer are well known. Indeed, these likenesses often preclude the diagnostic separation of primary cutaneous glandular neoplasms from metastatic mammary carcinomas, based on light microscopic and immunohistochemical features alone. To assess whether the presence of estrogen receptor protein (ERP) in breast carcinoma might serve as a diagnostic marker in this context, we analyzed 33 eccrine carcinomas, 24 sebaceous carcinomas, 15 intraepidermal apocrine carcinomas (extramammary Paget's disease), and 42 benign sweat gland tumors for ERP content. The monoclonal anti-ERP H222 was used with a modified avidin-biotin-peroxidase complex (ABC) method and paraffin sections. For comparison, eight cutaneous metastases of mammary carcinomas were similarly studied. ERP was identified in six of eight secondary neoplasms. However, this steroid-binding protein also was detected in 10 of 33 eccrine carcinomas. In three of 10 eccrine hidradenomas, each of two examples of hidradenoma papilliferum, and two of three chondroid syringomas, ERP-reactivity was noted as well. The remaining eccrine, apocrine, and sebaceous neoplasms were nonreactive. Among immunoreactive eccrine neoplasms, eight of 10 carcinomas occurred in males, whereas most ERP-positive benign eccrine tumors arose in females. The potential expression of ERP by sudoriferous malignancies reinforces the biologic similarities between mammary and cutaneous adnexal neoplasms. Moreover, ERP reactivity in the latter lesions underscores the inability of immunohistochemistry to distinguish primary and secondary glandular tumors of the skin with certainty.

Breast Neoplasms↗