Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer.

Semaphorins are a large family of evolutionarily conserved morphogenetic molecules that are associated with repelling axonal guidance. Intriguingly, recent researches indicate that semaphorins are involved in cancer progression. Semaphorin 4C (SEMA4C) has long been considered a neuronal migration gene, but we detected that it is also highly expressed in many malignant human cancers. During an investigation of subcutaneous tumor models, we found that SEMA4C expression promoted tumor growth and progression. We discovered that SEMA4C was involved in maintaining tumor cell self-renewal, likely by regulating the p53 pathway. Inhibiting the expression of endogenous SEMA4C in tumor cells impaired growth and induced senescence and cell-cycle arrest in the G2-phase. In addition, we found that SEMA4C induced the production of angiogenin and colony-stimulating factor-1 (CSF-1) in tumor cells by activating the NF-κB pathway in a plexinB2-dependent manner. In conclusion, SEMA4C expression in breast cancer cells promotes cancer cell proliferation, macrophage recruitment, and angiogenesis. Thus, inhibition of SEMA4C activity may be a novel therapeutic strategy for human breast cancer. IMPLICATIONS: In breast cancer, therapeutic targeting of the SEMA4C pathway may prevent tumor growth, angiogenesis, metastasis, and progression.

Synchronous Pulmonary Adenofibroma and Solitary Fibrous Tumor: Case Report and Review of the Literature.

Pulmonary adenofibroma (PAF) is a rare neoplasm that may be related to solitary fibrous tumor (SFT). A subset of PAFs harbor the NAB2-STAT6 fusion that is typical of SFT, but a significant proportion do not. Their distinction is clinically important as SFTs can potentially have an aggressive clinical course, while there has been no report of a PAF behaving in a malignant fashion. We report a case of a 60-year-old male who developed a SFT and PAF in the same lung. The SFT harbored a NAB2-STAT6 fusion, while the PAF did not have any identifiable fusion. This case represents the first instance of a single patient with both of these tumors occurring simultaneously in the same lung.

Glucocorticoid resistance syndrome caused by a novel NR3C1 point mutation.

Glucocorticoid resistance syndrome (GRS) is a rare genetic disorder caused by inactivating mutations of the NR3C1 gene which encodes the glucocorticoid receptor. The phenotypic spectrum is broad but typically include symptoms of adrenal insufficiency, mineralocorticoid excess and hyperandrogenism. We report a new case associated with a novel NR3C1 mutation. A 55-year-old woman with lifelong history of low body weight, hyperandrogenism and anxiety was seen at the endocrine clinic after left adrenalectomy and salpingoophorectomy for lesions suspicious of ovarian cancer and adrenal metastasis. The tumors turned out to be a 3.5 cm benign ovarian serous adenofibroma and a 3.5 cm multinodular adrenal mass. She complained of worsened fatigue and inability to recover weight lost with surgery. Pre-operative serum and urinary cortisol were elevated, but she had no stigma of Cushing's syndrome. Plasma ACTH was elevated and a 1-mcg cosyntropin stimulation test was normal. Her fatigue persisted over ensuing years and ACTH-dependent hypercortisolemia remained stable. Low dose oral dexamethasone failed to suppress endogenous cortisol. A pituitary MRI was normal but revealed incidental brain aneurysms. Bone densitometry showed profound osteoporosis. On the bases of this contradictory clinical picture, glucocorticoid resistance syndrome (GRS) was suspected. Using next generation sequencing technology, a novel heterozygous pathogenic variant in the NR3C1 gene was detected. We speculate that vascular malformations and profound osteoporosis, findings associated to cortisol excess, reflect in our patient a variable tissue sensitivity to glucocorticoids. In conclusion, in patients with clinically unexpected ACTH-dependent hypercortisolemia, primary glucocorticoid resistance (GRS) should be considered.

A comprehensive clinicopathological evaluation of the differential expression of microRNA-331 in breast tumors and its diagnostic significance.

OBJECTIVE: MicroRNA-331 (miR-331) has shown regulatory activity against several genes whose expression has been claimed to be deregulated in breast tumors, including that of epidermal growth factor receptor 2 (HER2). Herein, the clinical value of miR-331 expression was investigated by analyzing its levels in breast benign and malignant tumors. METHODS: The expression levels of miR-331 were quantified via real-time PCR in 130 malignant and 66 benign breast tissue specimens collected after surgical resection of primary tumors. The generated data were analyzed by applying several statistical tests in order to examine the relationship of miR-331 expression with various established clinicopathological features and survival data of patients. RESULTS: Our data showed that miR-331 was overexpressed in malignant breast tumors compared to their benign counterparts both overall (P = 0.026) and individually when the subgroups of fibroadenoma and invasive ductal carcinoma were analyzed with each other (P = 0.001). ROC curve analysis confirmed the diagnostic value of these variations, providing an AUC value equal to 0.597 (P = 0.026) and 0.663 (P = 0.001), respectively. Furthermore, miR-331 levels were elevated (P = 0.026) in ductal cancerous specimens compared to the lobular ones but failed to correlate with other clinicopathological features or survival data of the breast cancer patients. CONCLUSIONS: Our results provide evidence that miR-331 levels might provide valuable information regarding the differential diagnosis of benign and malignant breast tumors but present no prognostic value for breast cancer.

Biliary Adenofibroma of Liver: Morphology, Tumor Genetics, and Outcomes in 6 Cases.

Biliary adenofibroma is a rare primary hepatic neoplasm, recognized in the World Health Organization classification, although only 14 cases have been reported to date. This series includes extended follow-up from 2 of the early case reports and 4 novel cases. Clinical history and histology were reviewed in all 6 cases. Tumor DNA was analyzed for point mutations by multiplex polymerase chain reaction and copy number alterations by array comparative genomic hybridization. The patients included 4 females and 2 males presenting between 46 and 83 years of age, with tumors ranging from 7 to 16 cm in diameter. The tumors had similar morphology, with tubules and cysts lined mainly by bland to mildly atypical cuboidal epithelium embedded in fibrous stroma. Multiplex polymerase chain reaction did not identify mutations in 4 tumors tested. Three tumors tested by array comparative genomic hybridization showed chromosomal copy number alterations, including 1 with amplifications of CCND1 and ERBB2. Three patients underwent resection with no recurrence at 21, 20, and 3 years of follow-up. One patient is alive after 14 months with no resection. Two patients with margin-positive resections had local recurrence at 1 and 6 years after surgery. No patient had distant metastasis. The distinct morphology and multiple clonal cytogenetic alterations in biliary adenofibromas indicate that the lesions are neoplastic. Amplifications of CCND1 and ERBB2 are not typical of benign neoplasms, and suggest that these tumors may have the ability to behave aggressively. However, the clinical outcomes in these patients suggest the neoplasms are only slowly progressive.

Recurrent NAB2-STAT6 gene fusions and oestrogen receptor-α expression in pulmonary adenofibromas.

AIMS: Pulmonary adenofibromas are rare benign fibroepithelial tumours of the lung with unknown histogenesis and an indolent clinical behaviour. Their stroma resembles that of solitary fibrous tumours, whereas the glands are composed of respiratory epithelium organized in a phyllodes-like architecture. Differentiation of pulmonary adenofibromas from other more aggressive intrathoracic tumours is clinically relevant. However, their biology is unknown. Here, we sought to characterize pulmonary adenofibromas at a clinicopathological level and to define whether they could be underpinned by a highly recurrent somatic genetic alteration akin to tumours with similar morphology. METHODS AND RESULTS: Seven pulmonary adenofibromas were subjected to immunohistochemical analysis for thyroid transcription factor 1 (TTF1), napsin A, cytokeratin 7, E-cadherin, CD99, CD34, CD31, STAT6, oestrogen receptor (ER), progesterone receptor, androgen receptor, bcl-2, and vimentin, as well as electron microscopy and capillary sequencing on microdissected samples to evaluate the presence of NAB2-STAT6 fusion genes and MED12 exon 2 mutations in their discrete components. A control group comprising pulmonary solitary fibrous tumours, pulmonary hamartomas and breast fibroadenomas was also analysed. We confirmed that the stromal elements of pulmonary adenofibromas pertain to the fibroblastic lineage, and show ER overexpression in 71% of cases, whereas the epithelium consists of TTF1-positive, E-cadherin positive bronchiolar elements. A highly recurrent NAB2-STAT6 fusion variant (exon 4-exon 2) was detected in the stroma but not in the epithelium. No MED12 mutations were identified. CONCLUSIONS: Here, we demonstrate that pulmonary adenofibromas are neoplastic lesions harbouring the molecular hallmark of solitary fibrous tumours.

ACTN4 gene amplification and actinin-4 protein overexpression drive tumour development and histological progression in a high-grade subset of ovarian clear-cell adenocarcinomas.

AIMS: Actinin-4, encoded by the ACTN4 gene located on chromosome 19q13.2, enhances cell motility by bundling the actin cytoskeleton. We assessed how ACTN4/actinin-4 alterations contribute to the tumorigenesis of ovarian clear-cell adenocarcinomas (CCAs). METHODS AND RESULTS: Fluorescence in-situ hybridization analysis demonstrated that ACTN4 amplification (≥4 ACTN4 copies in ≥40% of cells) occurred in 27 (33%) of 81 CCAs and genomic gains of ACTN4 were associated strongly with immunohistochemical actinin-4 overexpression, poorly differentiated tumour histology and shorter patient survival (all P < 0.05). From the 27 ACTN4-amplified CCAs, 23 tumours with adjacent putative precursor lesions were selected and examined for ACTN4/actinin-4 alterations with respect to their intratumoral heterogeneity. In this selected cohort, none of the precursors lacking cytological atypia exhibited gains of ACTN4 or actinin-4 overexpression; 50% of the atypical endometrioses and 75% of the borderline CCAFs showed low-level gains of ACTN4 and actinin-4 overexpression, respectively. In 12 of 23 ACTN4-amplified CCAs, intratumoral heterogeneity for ACTN4 alterations was documented in carcinomatous components; the better differentiated carcinoma components exhibited fewer alterations than those with poorly differentiated histology. CONCLUSION: Accumulative genomic gains of ACTN4, causing actinin-4 protein overexpression, drive the development and progression of ovarian CCAs with high-grade histology.

Accumulative copy number increase of MET drives tumor development and histological progression in a subset of ovarian clear-cell adenocarcinomas.

Our previous study demonstrated that, among ovarian carcinomas, amplification of the MET gene and overexpression of MET specifically and commonly occur in clear-cell adenocarcinoma histology. This study was conducted to address how these alterations contribute to development and progression of this highly chemoresistant form of ovarian cancer. We histologically reviewed 21 previously described MET amplification-positive clear-cell adenocarcinoma cases, and selected 11 tumors with synchronous endometriosis and 2 tumors with adjacent clear-cell adenofibroma (CCAF) components. Using double in situ hybridization and immunohistochemistry, copy number alterations of the MET gene and levels of MET protein expression were analyzed in these putative precursor lesions and the corresponding invasive carcinoma components in this selected cohort. All of the non-atypical precursor lesions analyzed (ie, non-atypical endometrioses and the benign CCAFs) were negative for MET gain. However, low-level (≥3 MET copies in ≥10% and ≥4 MET copies in 10-40% of tumor cells) gain of MET was detected in 4 (40%) of the 10 atypical endometrioses and 1 of the 2 borderline CCAFs. Moreover, high-level (≥4 MET copies in ≥40% of tumor cells) gain of MET were detected in five (50%) of the atypical endometrioses. In 4 (31%) of the 13 cases enrolled, intratumoral heterogeneity for MET gain was documented in invasive carcinoma components, wherein all the relatively differentiated carcinoma components showed low-level gain of MET and all the corresponding poorly differentiated carcinomas showed high-level gain. The overall incidence of MET overexpression gradually increased from the precursors of non-atypical form (0%), through those of atypical form (67%) and the relatively differentiated carcinoma components (92%), to the poorly differentiated carcinoma components (100%). These results suggest that accumulative MET gene copy number alterations causing MET overexpression are associated with higher tumor grade and might drive the development and progression of the MET amplification-positive ovarian clear-cell adenocarcinoma.

Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations.

ARID1A is a recently identified tumor suppressor gene that is mutated in ∼50% of ovarian clear-cell carcinomas. This mutation is associated with loss of ARID1A protein expression as assessed by immunohistochemistry. The present study aimed at determining the timing of the loss of ARID1A protein expression during the development of ovarian clear-cell carcinoma and assessing its relevance in correlation to PIK3CA gene mutations. A total of 42 clear-cell carcinoma cases with adjacent putative precursor lesions (endometriosis-associated carcinoma cases (n=28) and (clear-cell) adenofibroma-associated carcinoma cases (n=14)) were selected and subjected to immunohistochemical analysis for ARID1A protein expression and direct genomic DNA sequencing of exons 9 and 20 of the PIK3CA gene. ARID1A immunoreactivity was deficient in 17 (61%) of the 28 endometriosis-associated carcinomas and 6 (43%) of the 14 adenofibroma-associated carcinomas. Among the precursor lesions adjacent to the 23 ARID1A-deficient carcinomas, 86% of the non-atypical endometriosis (12 of 14) and 100% of the atypical endometriosis (14 of 14), benign (3 of 3), and borderline (6 of 6) clear-cell adenofibroma components were found to be ARID1A deficient. In contrast, in the 19 patients with ARID1A-intact carcinomas, all of the adjacent precursor lesions retained ARID1A expression regardless of their types and cytological atypia. Analysis of 22 solitary endometrioses and 10 endometrioses distant from ARID1A-deficient carcinomas showed that all of these lesions were diffusely immunoreactive for ARID1A. Among the 42 clear-cell carcinomas, somatic mutations of PIK3CA were detected in 17 (40%) tumors and majority (71%) of these were ARID1A-deficient carcinomas. These results suggest that loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development, similar to the pattern of PIK3CA mutation recently reported by our group, and frequently coexists (not mutually exclusive) with PIK3CA mutations.

Copy number aberrations in benign serous ovarian tumors: a case for reclassification?

PURPOSE: Serous ovarian carcinomas are the predominant epithelial ovarian cancer subtype and it has been widely believed that some or all of these may arise from precursors derived from the ovarian surface epithelium or fimbriae, although direct molecular evidence for this is limited. This study aimed to conduct copy number (CN) analysis using a series of benign and borderline serous ovarian tumors to identify underlying genomic changes that may be indicative of early events in tumorigenesis. EXPERIMENTAL DESIGN: High resolution CN analysis was conducted on DNA from the epithelial and fibroblast components of a cohort of benign (N = 39) and borderline (N = 24) serous tumors using the Affymetrix OncoScan assay and SNP6.0 arrays. RESULTS: CN aberrations were detected in the epithelium of only 2.9% (1 of 35) of serous cystadenomas and cystadenofibromas. In contrast, CN aberrations were detected in the epithelium of 67% (16 of 24) of the serous borderline tumors (SBT). Unexpectedly, CN aberrations were detected in the fibroblasts of 33% (13 of 39) of the benign serous tumors and in 15% (3 of 20) of the SBTs. Of the 16 cases with CN aberrations in the fibroblasts, 12 of these carried a gain of chromosome 12. CONCLUSIONS: Chromosome 12 trisomy has been previously identified in pure fibromas, supporting the concept that a significant proportion of benign serous tumors are in fact primary fibromas with an associated cystic mass. This is the first high resolution genomic analysis of benign serous ovarian tumors and has shown not only that the majority of benign serous tumors have no genetic evidence of epithelial neoplasia but that a significant proportion may be more accurately classified as primary fibromas.

Epigenetic regulation of retinoic acid receptor ß2 gene in the initiation of breast cancer.

In order to investigate the methylation status of the retinoic acid receptor beta 2 gene (RAR-ß2) in breast carcinoma in relation to gene expression and clinicopathological parameters of patients with breast cancer, expression of RAR-ß2 gene and methylation status were analyzed in invasive carcinoma, atypical ductal hyperplasia, fibroadenoma specimens, and normal tissues. Our findings showed that RAR-ß2 expression was lower in the breast cancer compared to normal tissue and fibroadenoma. The methylation rate of RAR-ß2 in breast cancer and precancerous lesions of breast cancer were higher than that of normal tissues. Hypermethylation may be an initial step in breast carcinogenesis.

Aberrant expression of p27(Kip1)-interacting cell-cycle regulatory proteins in ovarian clear cell carcinomas and their precursors with special consideration of two distinct multistage clear cell carcinogenetic pathways.

We have previously reported that alterations of p27(Kip1)-interacting cell-cycle proteins frequently occur during the development of endometriosis-associated ovarian clear cell adenocarcinoma (CCA; Yamamoto et al., Histopathology in press, 20). However, CCA also occurs in association with clear cell adenofibroma (CCAF). In this study, the expressions of p27(Kip1)-interacting proteins, i.e., p27(Kip1), Skp2, Cks1, cyclin A, cyclin E, and the Ki-67 labeling index (LI), were analyzed in 25 CCAFs (11 benign and 14 borderline) and 15 CCAF-associated CCAs, and compared with the expression status of each protein in the 23 previously studied endometriosis-associated CCAs. Although aberrant expression of all p27(Kip1)-interacting proteins was more frequent in the CCAF-associated CCAs than in the benign CCAFs, statistical significance was found only for Cks1 overexpression. The frequencies of p27(Kip1) downregulation and overexpression of Skp2 and cyclin A were significantly lower in CCAF-associated than in endometriosis-associated CCAs (P < 0.05, respectively). The frequencies of p27(Kip1) downregulation and Skp2 overexpression in borderline CCAFs were significantly lower than those in atypical endometriosis components in endometriosis-associated CCAs (P < 0.05, respectively). Mean Ki-67 LI increased significantly through benign (4.9%) to borderline (11.1%) CCAF and to CCAF-associated CCA (30.6%), but the latter two values were significantly lower than those in atypical endometriosis (21.4%) and endometriosis-associated CCA (46.9%; P < 0.05, respectively). These data suggest that accumulated alterations of p27(Kip1)-interacting proteins may accelerate the development of CCAs regardless of their carcinogenetic pathways, but that tumor cells in the CCAF-associated pathway appear to show slower cell-cycle progression than those in the endometriosis-associated pathway, possibly accounting for the distinct clinicopathological features of the two CCA subtypes.

Clear-cell adenofibroma can be a clonal precursor for clear-cell adenocarcinoma of the ovary: a possible alternative ovarian clear-cell carcinogenic pathway.

Several studies have reported that ovarian clear-cell adenocarcinoma can be derived from endometriosis. Although the clear-cell adenofibroma (CCAF), a major form of benign and borderline ovarian clear-cell tumour, has been suggested as another precursor for clear-cell adenocarcinoma (CCA), there is no supportive genetic evidence for this presumption. To examine the genetic linkage between CCAF and CCA of the ovary, we conducted allelotype analysis for both CCAF and adjacent CCA components in 14 cases of CCA associated with benign CCAF and/or borderline CCAF. DNA isolated from laser-microdissected tissue was subjected to polymerase chain reaction and analysis for loss of heterozygosity (LOH), using 17 polymorphic markers located on 11 chromosomal arms: 1p, 5q, 8p, 9p, 9q, 10q, 11q, 13q, 18q, 19p and 22q. For all informative loci, the frequency of LOH in adenocarcinoma was 49% (54/110 loci), and was significantly higher than those in the components of benign CCAF (22%, 20/92 loci) and borderline CCAF (30%, 25/83 loci) (chi(2) test; p<0.05, respectively). The concordance rate in allelic patterns at all informative loci was 74% between benign CCAF and adenocarcinoma components, 81% between borderline CCAF and adenocarcinoma components, and 95% between benign CCAF and borderline CCAF components. Furthermore, between CCAF and adenocarcinoma components, an identical LOH pattern, involving the same alleles, was found in 13 (93%) of 14 cases at one or more chromosomal loci, and estimation of probability indicated that these events were very unlikely to have occurred by chance. Among the markers examined, LOHs on 5q, 10q and 22q were frequent in both CCAF and adenocarcinoma components, whereas LOHs on 1p and 13q were rare in CCAF components but frequent in adenocarcinoma components. These findings suggest that CCAF can be a clonal precursor for ovarian clear-cell adenocarcinoma.

Chk1 frameshift mutation in sporadic and hereditary non-polyposis colorectal cancers with microsatellite instability.

AIM: Protein kinase Chk1 (hChk1) is essential in human cells for cell cycle arrest in response to DNA damage, and has been shown to play an important role in the G2/M checkpoint. The BRAF mutations have been suggested to be linked with defective mismatch repair in colorectal cancers. The aim of this study was to investigate whether a frameshift mutation within the Chk1 gene contribute to the development or progression of eastern sporadic and hereditary non-polyposis colorectal cancer (HNPCC) with microsatellite instability (MSI). METHODS: We analyzed MSI using the 6 microsatellite markers and a frameshift mutation in the BRAF gene and in poly(A)9 within the Chk1 gene in 51 sporadic colorectal cancer and 14 HNPCC specimens. RESULTS: Eleven of the 51 sporadic colorectal cancers and all of the 14 HNPCCs were MSI-positive. Chk1 frameshift mutations were observed in 2 and 3 sporadic colon cancers and HNPCC, respectively, whereas no BRAF mutations were detected in these samples. Interestingly, all cases with the Chk1 frameshift mutation had high-frequency MSI. CONCLUSION: These results suggest that the Chk1 gene is a target of genomic instability in MSI-positive colorectal cancers and that the Chk1 framshift mutations might be involved in colorectal tumourigenesis through a defect in response to DNA damage in a subset of sporadic colorectal cancers and HNPCCs.

Molecular pathology of ovarian cancer.

Ovarian cancer is the leading cause of death among women with gynecologic malignancies. Epithelial tumors typically constitute 80-90% of ovarian malignancies and are classified primarily as serous, mucinous, endometrioid or clear cell. Current data indicate that each of these histologic subtypes is associated with distinct morphologic and molecular genetic alterations. We describe such genetic alterations with specific reference to histologic subtypes.

Biliary adenofibroma: a rare neoplasm of bile duct origin with an indolent behavior.

We report a case of biliary adenofibroma in a 47-year-old woman, who presented with right upper quadrant pain for several months. Abdominal imaging revealed a 16-cm solid and cystic mass in the left hepatic lobe. Histologically, the tumor showed two distinct components: 1) cystic and tubular structures lined by low columnar to cuboidal biliary-type epithelium, and 2) a dense fibrous stroma composed of spindle-shaped cells with only mild nuclear pleomorphism and inconspicuous nucleoli. Mitoses and stromal invasion were absent. The glandular epithelium stained positively for keratin AE.3/Cam 5.2, cytokeratin 7, cytokeratin 19, carcinoembryonic antigen, and epithelial membrane antigen and had a low Ki-67 proliferative index. In addition, the epithelium was positive for D10 but did not stain for 1F6 or acid mucin with alcian blue stain. This staining pattern, similar to bile duct hamartoma (von Meyenburg complex) with which this tumor shares morphologic similarity, suggests that biliary adenofibroma originates from interlobular or larger bile ducts. Three years after a subtotal resection no metastasis or significant tumor growth was noted. However, given the marked nuclear p53 immunoreactivity and tetraploidy status observed in this tumor, we cannot exclude that biliary adenofibroma may represent a premalignant process that warrants complete resection and thorough histopathologic examination.

Unexpected gynecologic neoplasms in patients with proven or suspected BRCA-1 or -2 mutations: implications for gross examination, cytology, and clinical follow-up.

Identification of inheritable mutations associated with the development of malignancy has led to prophylactic surgeries to remove tissues at risk. We report seven unrelated patients with family histories of breast and/or ovarian cancer, five of whom underwent prophylactic salpingo-oophorectomy with hysterectomy. Four had proven BRCA-1 or -2 mutations. Malignant cells were found unexpectedly in the peritoneal washings of two patients, leading to the discovery of early-stage fallopian tube carcinoma. After changing the sampling technique at our institution, two more cases of unexpected fallopian tube carcinoma in situ were discovered. Another patient had a significant family history and underwent hysterectomy for uterine fibroids, leading to the discovery of fallopian tube carcinoma. Another patient with BRCA-1 mutation had unexpected widespread primary peritoneal papillary serous adenocarcinoma. The final patient had a borderline malignant clear cell adenofibroma. These cases underscore the importance of peritoneal cytology and thorough sampling in the management of patients undergoing hysterectomy with a family history of breast/ovarian cancer and/or known BRCA-1/BRCA-2 mutations. As prophylactic surgeries are becoming more common secondary to advances in molecular diagnostics, pathologists need to be aware that surgical specimens from these patients may require more rigorous examination to uncover early neoplastic changes.

[Testicular feminization--sequelae of chronic neglect of a neoplastic process]. / Zur testikulären Feminisierung--Folgen langdauernder Verschleppung eines neoplastischen Geschehens.

This paper reports on a 56-year-old patient with a history of "testicular feminization syndrome" who was admitted to hospital because of a rapid gain in her abdominal girth (106 cm). A benign cyst was removed laparotomically which, histologically, was equivalent to a cystadenofibroma. Based on this case report, the clinical significance of testicular feminization syndrome and the necessity for gonadectomy due to the risk of growth of a possibly malignant tumor are discussed.