Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage

Endometriosis is a common gynecological disease in which tissue similar to the endometrium proliferates at sites outside the uterine cavity. Malignant transformation of endometriosis to endometrioid and clear cell ovarian carcinomas has been documented in histological studies, but no molecular genetic evidence exists to support that endometriosis is the clonal precursor of such malignancies. We examined 14 cases of endometriosis synchronous with ovarian cancer for loss of heterozygosity on 12 chromosome arms, X chromosome inactivation, and TP53 mutation to determine whether they shared genetic alterations. In all four of the cases where the carcinoma had arisen within endometriosis and in five of the seven cases where the carcinoma was adjacent to the endometriosis, common genetic lesions were detected, consistent with a common lineage. A TP53 mutation was also detected in one case of endometriosis adjacent to carcinoma. These findings support the numerous histological observations that endometrioid and clear cell ovarian carcinomas may arise through malignant transformation of endometriotic lesions.     

The clinical and pathological characters of malignant neoplasms arising from endometriosis

Eight cases of malignant tumors arising from endometriosis were reported; the ovary was the primary site in 7, whereas extragonadal site (rectum) in 1. The histologic classification was as follows: endometrioid carcinoma in 1. Clear cell carcinoma in 2, mixed clear cell carcinoma and endometrioid carcinoma in 2, mixed papillary cystadenocarcinoma in 1 and serous tumor of borderline malignancy in 1. The histologic pattern arising from endometriosis of the rectal wall was endometrioid adenocarcinoma with benign endometriosis contiguous to it. It was found that the ectopic endometrial tissue may undergo malignant change when they were under stimulation by some factors. One of which may be intrinsic or extrinsic estrogen, which may be related to the high incidence rate in this age group. Laparotomy should be done for assessing malignant change when ovarian mass was greater than 10 cm or grew rapidly. Five year survival rate will be expected to improved with postoperative progestin or irradiation. Preventive measures were also suggested.     

Impedance of a goat eye lens

Cyclins are essential proteins in cell cycle control, and their deranged expression has been reported to be associated with malignant transformation. Involvement of cyclins in the development of endometrioid carcinomas of the endometrium was studied immunohistochemically using antibodies against both cyclin A and tumor suppressor gene product p53, and their expression was compared with that of Ki-67 antigen. Sixty-two cases of endometrial endometrioid carcinoma and 20 cases of normal endometrium (10 proliferative and 10 secretory phase) were examined. Of the 62 endometrioid carcinomas, atrophic endometrium and hyperplasia were found adjacent to the cancers in 30 and 19 cases respectively. Cyclin A was expressed in < 1% of the glandular cells of normal endometrium in the proliferative phase and in hyperplasia, but was negligible in normal secretory phase and atrophic endometrium. p53 was almost always negative in normal endometrium and hyperplasia. Of the 62 endometrioid carcinomas, 12 tumors (19.4%) overexpressed cyclin A and 21 tumors (33.8%) overexpressed p53 (positive cells > 1%). Cyclin A and p53 were more frequently expressed in poorly differentiated tumors than in well differentiated tumors (cyclin A, p = 0.002; p53, p = 0.016). In addition, cyclin A-positive cells were topographically related to those cells positive for p53 as well as Ki-67. In conclusion, the abnormal expression of cyclin A and p53 is associated with high-grade endometrial endometrioid carcinomas.     

C4342T-mutation in the SCN4A gene on chromosome 17q in a Swedish family with paramyotonia congenita (Eulenburg)--correlations with clinical, neurophysiological and muscle biopsy data

Expression of P53 protein was determined in the process and the end of induction of malignant transformation in human fetal lung cells, with organic extract from tap water in a river of City G, to study its molecular mechanism. Results showed that the water sample of experimental doses could induce formation of cell malignant transformation foci to different extent and had certain toxicity to cells. High expression of P53 protein was observed in cell nuclei 15 days after exposure and before formation of cell transformation foci, or 30 days after exposure and formation of them. It suggests that changes of P53 protein may relate to cell malignant transformation to certain extent, and play some roles in the process of it.     

Villoglandular adenocarcinoma of the endometrium: a clinicopathologic study of 61 cases: a gynecologic oncology group study

Papillary endometrioid or villoglandular adenocarcinoma (VGA) is a relatively common type of endometrial adenocarcinoma, but studies describing its behavior have yielded conflicting results. Patients with a component of VGA were identified in a review of 819 women entered in a Gynecology Oncology Group Study (Protocol 33) of clinical stages I and II endometrial adenocarcinoma. Cases with coexisting foci of serous or clear cell carcinoma were excluded from further consideration. Of the 61 cases that formed the study sample, there were 24 with pure villoglandular differentiation and 37 who were admixed with typical endometrioid adenocarcinoma (EA). The general clinicopathologic features of patients with pure and mixed VGA are compared with 469 patients with pure EA. The VGAs were better differentiated (grade 1 or 2--97% of VGA versus 74% EA, p = 0.001). but they were not significantly different with respect to median age, depth of invasion, or frequency of nodal spread. Six of the 61 patients with VGA died of their tumor. The disease-specific survival rate at 3 years for VGA is 94% (95% confidence interval: 0.88-0.99) compared with 88% (95% CI: 0.86-0.91) for EA. Two of the patients who died had pure villoglandular tumors and four had mixed villoglandular and endometrioid carcinoma. In view of the frequent admixture of VGA and EA and their generally similar biological characteristics, with a prognosis similar to that of typical EA, we conclude that VGA should be considered a variant of EA.     

Sensitivity of myeloid progenitors to NK-cell depletion

AIMS: Cytomorphologic characterization of tumor cell subsets, according to the stage of pathologic differentiation, and comparison of cellular composition in tumor cyst and ascitic fluids were carried out on individual patients with ovarian endometrioid carcinoma. METHODS: A density gradient centrifugation technique was applied to fractionate the cells from tumor effusions. RESULTS: The enrichment of cell forms representing individual stages of pathologic differentiation by gradient centrifugation facilitated their cytomorphologic characterization. According to cytomorphologic features, 5 discrete cell subpopulations were identified and catalogued. The cellular composition of tumor cyst and ascitic fluids in individual patients was similar, but the number of fractions and percentage of cell subsets differed. CONCLUSIONS: The estimation of precise cytomorphologic criteria for cell forms in tumor effusions facilitated the cytologic diagnosis of ovarian endometrioid carcinoma. The possibility to concentrate poorly differentiated, frankly malignant cell subsets in low densities could significantly improve the diagnosis of tumor effusions.     

Magnetic resonance imaging of the female pelvis

Evaluation of pelvic pathology is an important part of most radiology practices. Magnetic resonance imaging (MRI) has proven itself to be a useful and cost-effective method in evaluating many of these diseases. This article reviews appropriate MR imaging techniques and findings of common gynecologic disorders. Uterine pathology is categorized into congenital anomalies, benign lesions (leiomyomas, adenomyosis, endometrial polyps, and nabothian cysts), and malignancies (endometrial and cervical carcinoma). Adnexal pathology reviewed includes endometriosis, polycystic ovaries, teratomas, and benign and malignant ovarian epithelial tumors.     

The relation of adenomyosis uteri to coexistent endometrial carcinoma and endometrial hyperplasia

The relation of adenomyosis uteri to endometrial carcinoma and endometrial hyperplasia has been the subject of only a few studies. These investigations have resulted in opposing conclusions on the association between the conditions. In this study of a 10-year period, all cases were retrieved from the surgical pathology laboratory files of adenomyosis uteri with either simultaneous endometrial carcinoma or endometrial hyperplasia. A control population was selected from patients who underwent hysterectomy for mechanical problems related to the uterus. Adenomyosis was found in association with endometrial carcinoma in 19.4% of 175 cases and in association with endometrial hyperplasia in 20.5% of 254 cases. The control series of 203 patients had a 16.7% incidence of adenomyosis. Statistical analysis showed no association between these conditions.     

Prostatic adenocarcinoma showing features of endometrioid and mucinous carcinomas: a case report

A 77-year-old male was admitted for the examination of post renal acute renal failure. Blood examination revealed renal dysfunction and elevation of carcinoembryonic antigen (CEA). Computed tomography and retrograde pyelography showed bilateral hydronephrosis due to ureteral stenosis. He died of renal failure and autopsy was done. Histologic findings showed moderately differentiated adenocarcinoma of the prostate associated with endometrioid and mucinous carcinoma, and metastases of retroperitoneal lymph nodes and multiple bones. Immunohistochemically, endometrioid carcinoma was positive for prostatic acid phosphate (PAP) and prostatic specific antigen (PSA), and negative for CEA. Mucinous carcinoma was negative for PAP and PSA, and positive for CEA. Including our case, 29 cases of endometrioid and 32 of mucinous carcinoma of the prostate reported in the Japanese literature are reviewed.     

Pure squamous cell carcinoma of the larynx with cervical nodal metastasis showing rhabdomyosarcomatous differentiation. Clinical, pathologic, and immunohistochemical study of a unique example of divergent differentiation

We describe a unique case of pure squamous carcinoma of the larynx that developed a cervical lymph node metastasis showing rhabdomyosarcoma admixed with squamous carcinoma (that is, carcinosarcoma). The rhabdomyosarcoma showed foci immunoreactive to multiple cytokeratin monoclonal antibodies, as well as to markers for striated muscle, thus indicating true divergent epithelial and rhabdomyosarcomatous differentiation. Although the morphogenesis of carcinosarcomas remains controversial, the sequence of events for the current case favors sarcomatous transformation of the original carcinoma (that is, sarcomatous neometaplasia of the primary carcinoma clone). The possible contributory role of radiation therapy in this case in inducing such a change is noted.     

Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas

We performed a multi-institutional, incident case-control study of 328 endometrioid and 26 serous carcinomas to assess whether risk factors and circulating hormone levels in women with serous carcinoma differ from the expected profile for endometrial carcinoma We also evaluated exposures potentially related to endometrial cancer risk, anthropometric measurements, and circulating levels of sex hormones and related carrier proteins. Histopathologic specimens were reviewed without knowledge of the other data. As expected, a statistically significant association was observed for high body mass index (BMI) (relative risk, 3.5) and use of menopausal estrogens (relative risk, 2.4) in the endometrioid carcinoma cases, whereas serous carcinomas were not strongly associated with these factors. Smoking and oral contraceptive use decreased risk for both tumor types. For five of six sex hormones tested, age-adjusted mean serum levels in patients with serous carcinoma were significantly lower than those in women with endometrioid carcinoma. After adjustment for BMI, these differences were narrowed, but levels of albumin-bound estradiol and estrone remained significantly lower in the serous cases. Age and BMI-adjusted levels of sex hormone-binding globulin were significantly higher in patients with serous carcinoma than in women with endometrioid carcinomas. In conclusion, risk factors and sex hormone levels in patients with uterine serous carcinoma seem to differ from those in women with endometrioid carcinoma, suggesting that there may be at least two different pathways of endometrial carcinogenesis.     

Miscellaneous types of surface epithelial neoplasms. The well-differentiated end of the morphologic spectrum of endometrioid, clear-cell, and Brenner tumors and mixed epithelioid tumors of low malignant potential of müllerian type

Benign ovarian neoplasms with endometrioid or clear-cell differentiation are rare, but benign Brenner tumors are not unusual. A subgroup of endometrioid, clear-cell, and Brenner neoplasms, characterized by morphologic features intermediate between benign and malignant, has been labelled by various investigators as borderline, of low malignant potential (LMP), or proliferating. This chapter reviews the definition of each of these cell types, evaluates the significance of the LMP category, and concludes with a discussion of well-differentiated ovarian neoplasms with mixed differentiation of the müllerian type.     

Nutritional status of participants in the Giessen Senior Long-Term Study with respect to antioxidant vitamins and selenium

The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous cell carcinoma development by enhancing activation, amplification, and overexpression of pre-existing oncogenes within neoplastic tissues. Because of the integral role of viruses in malignant transformation of host cells, innovative antiviral therapy may prevent tumour development, involute neoplastic proliferations, or arrest malignant progression.     

Adenoid basal carcinoma of the cervix uteri: a case report

We report a rare case of adenoid basal carcinoma of the uterine cervix, unexpectedly found in a uterus resected for the treatment of cervical intraepithelial neoplasia (CIN) 3. The patient was a 47-year-old Japanese female. She received a total abdominal hysterectomy under a diagnosis of CIN 3 of the cervix. Grossly, there were no significant findings in the surgical specimens. Microscopically, in seven of the 12 blocks of the cervix examined, scattered small nests of uniform small cells, which extended 4 mm below the epithelial surface, with dark nuclei and scant cytoplasm were observed. Peripheral palisading as well as the formation of gland-like or acinar structures were noted. The latter were positive for mucicarmine. Stromal reaction was not obvious. There were also foci of squamous differentiation in some portions of the small nests. Occasional mitoses as well as large atypical cells were also seen in this area. Immunohistochemically, the foci of squamous differentiation were positive for carcinoembryonic antigen. The epithelial surface in other portions showed CIN 3 with crypt extension. Distinction between adenoid basal carcinoma of the cervix and other diseases, such as adenoid cystic carcinoma and squamous cell carcinoma with basaloid features, is important for clinical management because the clinical behavior of adenoid basal carcinoma is less malignant.     

Fatal thyroid carcinoma. Anaplastic transformation of adenocarcinoma

Prognosis of well-differentiated carcinoma of the thyroid gland is generally favorable, while that of anaplastic carcinoma, extremely poor. Well-differentiated carcinoma may sometimes be fatal; the most common underlying cause is considered to be due to anaplastic transformation of the original well-differentiated carcinoma to a less differentiated form. We studied 27 consecutive autopsy cases of fatal thyroid cancer treated at the Ito Hospital, Tokyo, during a five-year period, 1969-1973. We found uniform histological features of anaplastic carcinoma in 10 cases and of well differentiated carcinoma in four cases. In addition, co-existence of well-differentiated and anaplastic carcinomas was observed in nine cases and well differentiated and squamous cell carcinomas in four. Circumstantial evidence strongly suggests that malignant transformation is a part of the natural history of thyroid carcinoma, from well-differentiated carcinoma to less differentiated forms, either squamous cell or anaplastic carcinoma.     

Implication of the glycoxidation and lipoxidation reactions in the pathogenesis of dialysis-related amyloidosis (Review)

BACKGROUND: The term Marjolin ulcer is now synonymous with malignant transformation of chronic ulcers, sinus tracts, and burn scars. OBJECTIVE: To illustrate the importance of incisional or excisional biopsies in cases of suspected burn scar carcinoma. METHODS: Case report and review of the literature. RESULTS: Multiple punch biopsies were negative while a complete excision revealed the diagnosis of squamous cell carcinoma. CONCLUSION: Because of the focal nature of malignant change in burn scars, incisional or excisional biopsy should be performed.     

Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma

BACKGROUND: Prostate carcinoma usually is heterogeneous and multifocal, with diverse clinical and morphologic manifestations. Understanding of the molecular basis for this heterogeneity is limited, particularly for the putative precursor, high grade prostatic intraepithelial neoplasia (PIN). In this study, the authors attempted to determine the genetic relation between multiple foci of PIN and matched foci of carcinoma, and whether they are independent in origin. METHODS: The distribution and prevalence of allelic imbalance at 6 microsatellite polymorphic markers on chromosomes 7q, 8p, 8q, and 18q were examined in 84 microscopically excised PIN foci (mean, 1.6 foci/case) and 95 foci of prostate carcinoma (mean, 1.8 foci/case) from 52 completely embedded, mapped whole mount prostates. RESULTS: PIN contained a lower overall proportion of allelic imbalance than matched prostate carcinoma foci for the 6 polymorphic microsatellite markers (65% vs. 82%), but this difference was not significant. The rate of allelic imbalance in PIN was similar to that in prostate carcinoma at 5 of 6 loci studied; the exception, D18S34 (18q12.2-12.3), had a significantly lower rate of allelic imbalance in PIN than in prostate carcinoma (19% vs. 52%), suggesting that genetic alterations in this chromosomal region may be important in carcinogenesis. Of 22 cases with allelic imbalance in at least 1 focus of PIN and 1 focus of prostate carcinoma, 21 informative cases (95%) showed a similar pattern of allelic imbalance at > or = 1 markers in the matched PIN and prostate carcinoma foci. Significant genetic heterogeneity was observed in both PIN and prostate carcinoma. Allelic imbalance was observed in at least 1 focus in 11 of 25 cases with multiple foci of PIN (44%) and 20 of 25 cases with multiple foci of prostate carcinoma (80%). There was no significant correlation between allelic imbalance and pathologic stage or tumor grade. CONCLUSIONS: Our findings indicate that multiple foci of PIN arise independently within the same prostate. This observation suggests that a field effect underlies prostatic neoplasia. Multiple foci of prostate carcinoma also often arise independently, lending additional support for this hypothesis. The strong genetic similarities between PIN and prostate carcinoma strongly suggest that evolution and clonal expansion of PIN may account for the multifocal etiology of carcinomas.     

Consideration on a case of carcinoma ex pleomorphic adenoma of the parotid gland

The authors report a case of carcinoma in an ex pleomorphic adenoma of the parotid gland that was recently referred to their attention. This form of carcinoma is not very frequent and in the literature it is reported in a percentage of cases ranging from 1.5 to 12%. The pathogenesis of this neoplasia is controversial and at the present state of the art there are authors who support the hypothesis of a malignant transformation of a previous pleomorphic adenoma, and those who sustain the onset of the tumour ex novo. At present, there is a tendency to differentiate the carcinoma ex pleomorphic adenoma from the malignant mixed tumour: the histological analysis of the former in fact shows a benign stromal component typical of pleomorphic adenoma associated with a malignant epithelial component, whereas in the malignant mixed tumour both the mesenchymal and epithelial components are malignant. The authors use this case report as a starting point to review their 20-year experience, of pleomorphic adenoma in order to evaluate the behaviour of this tumour, above all in relation to the phenomenon of recidivation and cancerization. They report recidivation in 3.5% of cases and no malignant degeneration. The surgical approach used varied depending on the site and size of the neoformation, as well as on whether the tumour was primary or recurrent.     

Endometrioid carcinoma arising in a scar of caesarean section. Case report

Endometriosis of a surgical scar is rare and occurs mainly when a hysterectomy has been performed in the past. Development of malignancy in such a lesion is very unusual. A rare case of primary endometrioid carcinoma in the endometriosis of a caesarean scar is described.