Biomedical subjects
Publications and source records attributed to C A Axiotis.
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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.
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.
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.
Duodenal gastrinomas are increasingly found at surgery, yet information about their location and characteristics is based on the results of either pooled series or retrospective reviews of small numbers of selected cases. To address these issues we have analyzed the location, incidence, and malignant potential of duodenal gastrinomas in 65 consecutive patients who underwent removal of all tumor as part of a 10-year prospective study to resect gastrinomas in patients with sporadic Zollinger-Ellison syndrome. The primary gastrinoma was located in the duodenum in 24 patients (37%). There were 19 men and five women aged 32 to 69 years (mean 49.4 years), with symptoms for 0.6 to 35 years (mean 7.9 years). Preoperative studies included serum gastrin levels of 114 to 35,798 pg/ml (mean 2060 pg/ml), basal acid output of 7 to 95 mEq/hr (mean 37.6 mEq/hr), and a positive secretin test result in 22 patients. Preoperative imaging studies identified tumor in the duodenal area in 11 patients (46%), but most positive imaging findings were metastatic gastrinoma in lymph nodes, and the primary duodenal tumor itself was identified in only two patients. Portal venous sampling had a localizing gastrin gradient in the inferior or superior pancreaticoduodenal vein in 17 of 23 patients (74%). Each of the 24 patients had a single, small duodenal wall tumor of 2.8 to 10.1 mm diameter (mean 6 mm). Each tumor stained positive for gastrin by immunohistochemistry. Seventeen tumors (71%) were located in the first portion of the duodenum, five (21%) in the second, and two (8%) in the third. Each tumor originated in the submucosa, and 13 (54%) were limited to the submucosa, whereas 11 (46%) were locally invasive, four (16%) extending into the muscularis mucosa and seven (29%) into the muscularis propria. Thirteen patients (54%) had spread to regional lymph nodes, whereas two (8%) had liver metastases. Lymph node metastases were seen with larger duodenal tumors (mean 7.1 vs 5.4 mm; p less than 0.01). The data suggest that a single duodenal wall gastrinoma is a common cause of Zollinger-Ellison syndrome (37%). These small (less than 1 cm) tumors are located in the submucosal layer of the proximal duodenum (92%) and are malignant more often than previously thought (54%).
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.
The authors report a case of primary bronchial malignant melanoma, occurring in a 34-year-old woman presenting with persistent cough. At bronchoscopic examination, a polypoid mass was found to occlude the left mainstem bronchus. Biopsies showed a malignant epithelioid tumor resembling an atypical carcinoid. Histochemistry, electron microscopic study, and immunohistochemistry confirmed the diagnosis of melanoma. Physical examination and additional clinical history to exclude other possible primary sites were negative. The patient underwent thoracotomy with left pneumonectomy. Nineteen months after resection she was found to have a histologically similar tumor involving her left adrenal gland. Review of the literature shows that melanoma of the lower respiratory tract has been reported only in adults and has a tendency to present as a central polypoid growth that may be responsive to surgical resection.
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Endosalpingiosis within the muscularis propria of the distal vermiform appendix was discovered in an appendectomy specimen removed during exploratory laparotomy for inflammatory tubal disease. Endosalpingiosis has not been previously reported in the appendix. The pathogenesis and possible significance of this lesion are discussed.
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We report multifocal cutaneous and mucosal vascular proliferations with the clinical and histological features of lobular capillary hemangioma and histiocytoid hemangioma in a 32-year-old acquired immunodeficiency syndrome patient. The lesions resolved subsequent to erythromycin therapy.
The production of tumors through solid-state mechanisms has been demonstrated in experimental animals, but foreign body tumorigenesis has not been proven definitively in man. The authors report three patients with angiosarcoma that occurred in intimate association with foreign material retained for prolonged periods. Although several etiologic factors have been defined in angiosarcoma, foreign bodies generally are not appreciated to have this potential. Review of the literature disclosed six cases of angiosarcoma and 40 cases of sarcomas of other histologic types associated with foreign material, with latency periods of from 4 months to 63 years. Implanted foreign material thus should be considered capable of inducing virtually any form of sarcoma in humans.
A 51-year-old man was found to have two separate intratesticular serous cystadenomas of low malignant potential. Electron microscopy and OC 125 antibody reactivity characterize the neoplasms as serous and suggest müllerian histogenesis.
Pathological and clinical features in early localized mucinous and nonmucinous bronchiolo-alveolar carcinomas (BAC) have not been adequately compared. In an attempt to characterize such lesions, we studied the clinicopathological, ultrastructural, and immunohistochemical features of three mucinous and eight nonmucinous BAC (four Clara cell, four Type II pneumocyte) along with one sheep pulmonary carcinoma (SPC). Tumor border, associated fibroplasia, tumor cell incohesion, lymphocytic infiltrate, T-lymphocytes, Langerhans cells (LC), and Leu-M1 and OC 125 immunoreactivity were evaluated. Localized tumors of both types had a similarly favorable prognosis, even when the tumor size was greater than 3 cm or showed more complex histology. Type II pneumocyte carcinomas with tumor cell disassociation and desquamation or a pseudomesotheliomatous phenotype did poorly. Clara cell and type II carcinomas elicited an LC and T-lymphocyte immune response. LC and T-lymphocytes were absent in mucinous BAC and SPC. All of the three mucinous and three of the seven nonmucinous BAC were Leu-M1 negative, indicating that Leu-M1 may not distinguish between BAC and mesothelioma, especially in a small biopsy specimen. Tumors with absent or slight Leu-M1 immunoreactivity had a favorable outcome irrespective of cell type and presence or absence of LC. Inasmuch as OC 125 was negative in all cases of BAC, OC 125 may be a useful adjunct in the immunodiagnosis of mesothelioma. Our investigation supports the view that two different groups of tumors are assembled under the single nosologic entity of BAC: one, mucinous, which grows along an unaltered pulmonary alveolar framework and elicits a B-lymphocytic response, and the other, nonmucinous, which induces desmoplasia and elicits an LC and T-lymphocytic response. Only mucinous BAC represent a biologic entity distinct from conventional pulmonary adenocarcinomas.
An 87-year-old man was found to have a lymphoma in the deep soft tissue of the right shoulder with concomitant central nervous system involvement. There was no evidence of cutaneous, peripheral lymph node, mediastinal, abdominal, or bone marrow involvement. Light microscopic, ultrastructural, and immunohistochemical evaluation characterized the neoplasm as a peripheral T-cell lymphoma. Lymphomas presenting in soft tissue are rare, and the few well-documented cases in the literature are of B-cell origin. We report a T-cell lymphoma presenting in the soft tissue of the extremity, and delineate its clinicopathologic features.
A 24-year-old woman with severe Cushing's syndrome was found to have corticotroph cell pituitary adenoma arising within a benign cystic ovarian teratoma. The patient manifested sustained hypercortisolemia and lack of suppression of either adrenocorticotropin (ACTH) or cortisol production. There was no evidence of a pituitary mass or secretion of other hormones. After careful clinical evaluation, no other tumor masses were found. Resection of the ovarian tumor led to normalization of ACTH and cortisol levels. Densely granulated corticotroph tumor cells with prominent Type I microfilaments and intracytoplasmic ACTH immunoreactivity characterized the neoplasm as a pituitary corticotroph cell adenoma. This is, to our knowledge, the first case reported of a functioning pituitary adenoma arising within a benign cystic teratoma.
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Bronchioloalveolar carcinomas (n = 45), intravascular bronchiolo-alveolar tumors (n = 8), and sclerosing hemangiomas of the lung (n = 2) were stained for surfactant apoprotein by the immunoperoxidase method. Of the bronchiolo-alveolar carcinomas, 12 were found to be carcinomas of type II pneumocytes and the remaining 33 tumors were designated as nontype II pneumocytic bronchiolo-alveolar carcinomas. Twenty-five of these tumors displayed trapped benign type II pneumocytes within the tumor masses. In the case of intravascular bronchioloalveolar tumors, none of the tumors demonstrated staining of tumor cells for surfactant apoprotein. In the two cases of sclerosing hemangiomas, the type II pneumocytes were exuberant and numerous, and in one case contained intranuclear inclusions of surfactant apoprotein. This article discusses the implication of the presence of benign type II pneumocytes in pulmonary tumors.