Cytoplasmic Pattern p53 Immunoexpression in Pelvic and Endometrial Carcinomas With TP53 Mutation Involving Nuclear Localization Domains: An Uncommon But Potential Diagnostic Pitfall With Clinical Implications.

A cytoplasmic pattern of p53 immunohistochemical expression has recently been reported in a rare subset of pelvic and endometrial cancers with a TP53 mutation involving domains affecting nuclear localization. This study reports the clinicopathologic features of 31 cases with a TP53 mutation involving nuclear localization, the largest study to date, emphasizing practical strategies for recognizing this uncommon variant and distinguishing it from the p53 wild-type pattern. The study also evaluates the prognostic significance of TP53 mutation involving nuclear localization in the ovarian high-grade serous carcinoma (HGSC) cohort of The Cancer Genome Atlas database. Most of the 31 tumors were advanced stage pelvic or endometrial HGSC. All TP53 mutations were predicted to result in loss of function. The p53 overexpression pattern was present in 6 tumors; the p53 null pattern in 3 and the p53 cytoplasmic pattern in 22 tumors. The p53 cytoplasmic pattern predominantly consisted of weak to moderate cytoplasmic staining in >95% of tumor cells as well as variable intensity nuclear staining involving a range of just a few cells to just under 80% of tumor cells. The p53 cytoplasmic pattern was observed in 100% of tumors with TP53 mutation in the nuclear localization domain and in 33% to 44% of tumors with a mutation in the adjacent tetramerization domain or nuclear exclusion sequence (P<0.01). p16 immunoexpression was present in 74% of tumors. In The Cancer Genome Atlas ovarian HGSC cohort, 9% of 471 nonredundant TP53-mutant cases had a nuclear localization domain, tetramerization domain, or nuclear exclusion sequence mutation but there was no significant difference in survival when compared to cases with TP53 mutation outside those domains (P>0.05). p53 cytoplasmic staining merits classification as an aberrant result despite coexisting nuclear staining that in some cases may resemble the p53 wild-type pattern. While positive p16 immunostaining may be of value to confirm diagnostically challenging cases of p53 cytoplasmic staining, a negative result is noninformative and molecular testing for TP53 mutation should be considered, if available.

Embryonal rhabdomyosarcoma within abdomen and pelvis in an adult.

Rhabdomyosarcoma arising in abdomen and pelvis is an uncommon but important type of soft tissue sarcoma, posing a great challenge for clinicians. Sporadic cases of intra-abdominal rhabdomyosarcoma were reported, but mostly in pediatrics. We demonstrated a rare case of primary abdominopelvic rhabdomyosarcoma in an elderly woman who presented with a notable increase in abdominal circumference and constipation. Abdominal magnetic resonance imaging showed a huge mass throughout the abdomen and pelvis. Cytoreductive surgery was performed by gynecologists due to the suspicious diagnosis of disseminated leiomyosarcoma. However, the final pathological analysis revealed embryonal rhabdomyosarcoma. Although adjuvant chemotherapy was administered, localized recurrence was identified 6 months after the initial operation. Gynecologists and radiologists should be aware of it so it can be listed in the differential diagnosis of masses that primarily arise in the abdomen and pelvis.

Central Nervous System-type Neuroepithelial Tumors and Tumor-like Proliferations Developing in the Gynecologic Tract and Pelvis: Clinicopathologic Analysis of 23 Cases.

Central nervous system (CNS)-type tumors and tumor-like proliferations arising in the gynecologic tract and pelvis are rare. Clinicopathologic features of 23 cases are reported using the current WHO classification system for CNS tumors, with selected relevant immunohistochemical and molecular genetic analyses when possible. There were 12 embryonal tumors, including 7 medulloepitheliomas, 2 embryonal tumors (not otherwise specified), 1 embryonal tumor with multilayered rosettes, 1 embryonal tumor with features of nodular desmoplastic medulloblastoma, and 1 medulloblastoma with extensive nodularity, with primary sites including ovary (7), uterus/endometrium (3), and pelvis (2). Six ovarian tumors had associated germ cell tumors (3 immature teratomas [1 also with yolk sac tumor], 2 mature cystic teratomas, and 1 yolk sac tumor). These tumors typically had some expression of synaptophysin (10/10), GFAP (5/9), S100 (3/6), and NeuN (3/3) and were negative for C19MC amplicon by fluorescence in situ hybridization (0/5). There were 6 glial tumors, including 3 ependymomas (1 anaplastic), 1 oligodendroglioma, not otherwise specified, 1 pilocytic astrocytoma, and 1 atypical glial proliferation after therapy of a high-grade high-stage immature teratoma, with primary sites including ovary (4), fallopian tube (1), and pelvic sidewall (1). Four ovarian tumors had associated teratomas (2 immature and 2 mature). These tumors expressed GFAP (5/6), OLIG2 (2/3), and S100 (1/1), and the pilocytic astrocytoma was negative for BRAF (V600E) mutant protein. There were 4 neuronal or mixed glioneuronal tumors, including 3 neurocytomas and 1 malignant (high-grade) glioneuronal neoplasm, all primary ovarian and associated with teratomas (3 mature, 1 immature). These tumors expressed synaptophysin (4/4), GFAP (1/3), NeuN (1/2), and OLIG2 (1/2). Single-nucleotide polymorphism microarray analysis of the malignant glioneuronal neoplasm demonstrated a partial deletion at location (1)(p36.23p35.2) on chromosome 1p, and 2 regions of deletion at locations (19)(q11q13.12) and (19)(q13.41qter) on 19q. One neurocytoma had no 1p and 19q co-deletions. There was 1 meningioma in the pelvis. For 10 patients with embryonal tumors and follow-up, 5 were alive with no evidence of disease (mean/median: 60/52 mo), 4 were alive with recurrent disease (mean/median: 32/31 mo), and 1 died of disease (13 mo). For 5 patients with other tumor types and follow-up, all were alive without evidence of disease (mean/median: 33/30 mo). Diagnostic evaluation and classification per systems used for primary CNS tumors are recommended for the wide spectrum of CNS-type neuroepithelial tumors that can occur in the female genital tract and pelvis.

[Late Relapse of Testicular Cancer at the Pelvis with Elevated AFP Levels : A Case Report].

We report a patient with seminoma which recurred as late relapse at the pelvis with elevated alphafetoprotein (AFP) levels. A 40-year-old man presented with a left testicular tumor and subsequently underwent high orchiectomy in 2006. Pathological findings showed that the tumor was a seminoma with invasion into the tunica albuginea (pT2N0M0). Seven years after surgery, computed tomography showed a 12×8.7 mm, well-circumscribed, pelvic cystic tumor, and AFP and human chorionic gonadotropin levels were elevated. He was clinically diagnosed with recurrent testicular cancer. Despite the fact that the patient had four courses of bleomycin, etoposide, and cisplatin (BEP), the tumor enlarged and AFP levels were still elevated. Therefore, we performed open excision of the pelvic tumor. Judging from the pathological report, we made the final diagnosis of mature cystic teratoma. The patient was free of recurrence or metastasis within 48 months of follow-up.

Asymptomatic uterus-like mass (ULM) of the extraperitoneal space - a case report of a rare finding with unusual clinical presentation and review of the literature.

The paper presents a case of a uterus-like mass (ULM), a rare type of tumour of the female reproductive system, which did not present any clinical symptoms described in other cases of ULMs. There are 35 reported cases of this type of tumour. It is defined as a lesion composed of smooth muscle-like stromal cells with a central cavity lined with endometrial type epithelium. There are three theories on the pathogenesis of ULMs which we discuss along with clinical presentation, diagnostic features, treatment options and potential oncological implications of this type of tumour, based on our case, and the review of the literature.

Cellular fibroma in the Douglas cavity, mimicking a malignant neoplasia: fibroma, fibrosarcoma or mitotically active cellular fibroma?

INTRODUCTION: Ovarian fibroma is a benign stromal tumour composed of spindle/ovoid fibroblastic cells producing collagen. Approximally 10% of fibromas are densely cellular with small amount of collagen. In these cases, if mild nuclear atypia is present, they are best addressed as cellular fibroma. However cellular fibroma may show a greater mitotic activity and therefore they should be referred as mitotically active cellular fibromas. Mostly benign, it is necessary to differentiate them from malignant tumours such as fibrosarcomas. METHODS: We report a case of an unusual presentation of mitotically active cellular fibroma, detected in the Douglas cavity of a young woman, with normal appearing ovaries and uterus, mimicking a malignant neoplasia clinically and on imaging. In fact abdominal mass may be associated with acute pain, resulting in clinical emergency, really difficult to distinguish from a frank malignancy, before surgical procedure. RESULTS: We described the clinical, radiological and pathological characteristics of our case and we make a comparison of what previously described in literature. DISCUSSION: The differential diagnosis among those entities is based on the microscopic features such as atypia and the number of mitoses. However, according to their dimensions, it may be necessary to generously sample these tumours and sometimes, to perform a panel of immunohistochemical markers, in order to make a correct diagnosis, establish the best treatment and the right follow-up. In fact, the prognosis is not certain, due to the possible recurrence, especially if not completely excised.

ACTH-secreting pancreatic neuroendocrine carcinoma with ovarian and pelvic metastases causing Cushing's syndrome: a case report.

Adrenocorticotropin hormone (ACTH)-secreting pancreatic neuroendocrine carcinoma (NEC) with ovarian and pelvic metastases causing Cushing's syndrome is very rare and might be misdiagnosed. We describe a case of ACTH-secreting pancreatic poorly differentiated NEC developing bilateral ovarian and pelvic metastases. A 27-year-old woman presented with thirst, polydipsia, fatigue and poorly controlled hyperglycemia. Laboratory and imaging investigations revealed hypokalemia, hyperglycaemia, ACTH-dependent hypercortisolemia and a 12-cm mass at the junction of body and tail of the pancreas with ovarian and pelvic nodules. The patient underwent partial pancreatectomy and splenectomy, uterectomy, bilateral oophorectomy, and excision of peritoneal nodules. Tumors in pancreas, ovaries and pelvis were diagnosed as poor-differentiated NEC. After 19-month chemotherapy, she developed pelvic metastasis. The tumor in our case is a large, poorly differentiated NEC secreting ACTH and causing CS, with ovarian metastases. To our knowledge, this new additional case of ACTH-secreting pancreatic NEC with ovarian metastases would add to the better understanding of this tumor.

Hemangioblastoma of pelvic cavity: report of a case and review of literature.

Hemangioblastoma of soft tissue is a very rare tumor of uncertain histological type. Herein, we reported a 51-year-old woman was found to have a solid and cystic mass measuring 31×30 mm in the right adnexa area on a computed tomography scan. The tumor showed the typical histology of hemangioblastoma. Tumor was composed of numerous capillaries and stromal cells with cytoplasmic vacuolization. Immunohistochemical study revealed that the tumor stromal cells were positive for CD56, S-100 protein, NSE, Syn, CgA, and inhibin-α. Focal EMA positivity was present. Ki-67 expression was found in approximately 1% of tumor cells. The tumor cells were negative for CK, HMB-45, Melan-A, SMA, and CD68. The differential diagnosis of Hemangioblastoma arising in pelvic cavity includes hemangioma, hemangioendothelioma, liposarcoma, renal cell carcinoma, fat-forming solitary fibrous tumor, paraganglioma, and perivascular epithelioid cell tumor (PEComa).

Malignant gangliocytic paraganglioma of the duodenum with distant metastases and a lethal course.

Gangliocytic paraganglioma (GP) is rare and has been regarded as benign in general with a good prognosis. We present a patient with duodenal GP showing a malignant and lethal clinical course. A 47-year-old male patient was found to have a duodenal tumor and enlarged regional lymph nodes. The patient initially underwent a pancreaticoduodenectomy to resect the tumor and involved lymph nodes completely. Histological and immunohistochemical analyses showed findings typical of GP. However, the distant metastatic lesions in the liver and pelvic cavity were rapidly observed after surgery. The patient underwent chemotherapy and radiotherapy, as well as a second surgery to partly remove the metastatic mass in the pelvic cavity. The histological examination revealed no significant difference in histological features between the primary duodenal tumor and the metastatic pelvic mass. However, the patient finally died of the tumor due to the recurrence of the residual pelvic lesion and increased liver mass. To our knowledge, this is the first report of lethal GP with multifocal metastases. Our case confirms that GP should be regarded as a malignant potential tumor with behavior code of "1", rather than a benign tumor of "0".

Giant pelvic angiomyofibroblastoma: case report and literature review.

Angiomyofibroblastoma (AMF) is a rare, benign, soft-tissue tumor, which predominantly occurs in the vulvovaginal region of middle-aged women. It is clinically important to distinguish an AMF from other stromal cell lesions. Here, we report the case of a 32-year-old woman with a rare, giant pelvic AMF, which showed a benign clinical course. The tumor was located in the cul-de-sac of Douglas. It was well demarcated, hypocellular, edematous and composed of spindle-shaped and oval stromal cells aggregating around thin-walled blood vessels. The tumor cells had abundant eosinophilic cytoplasm, and expressed estrogen receptors, progesterone receptors and desmin. Mitotic figures were absent. It is important to distinguish AMFs from aggressive angiomyxomas because both occur at similar sites but show different clinical behaviors. Most AMFs and aggressive angiomyxomas have the same immunohistochemical phenotype. The well-circumscribed borders of AMF are the most important characteristic that distinguish it from aggressive angiomyxomas. AMFs rarely recur after complete surgical excision. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5510813471244189.

Solitary fibrous tumors in abdomen and pelvis: imaging characteristics and radiologic-pathologic correlation.

AIM: To describe the imaging features of solitary fibrous tumors (SFTs) in the abdomen and pelvis, and the clinical and pathologic correlations. METHODS: Fifteen patients with pathologically confirmed SFTs in the abdomen and pelvis were retrospectively studied with imaging techniques by two radiologists in consensus. Patients underwent unenhanced and contrast-enhanced imaging, as follows: 3 with computed tomography (CT) and magnetic resonance imaging (MRI) examination, 8 with CT examination only, and 4 with MRI examination only. Image characteristics such as size, shape, margin, attenuation or intensity, and pattern of enhancement were analyzed and correlated with the microscopic findings identified from surgical specimens. In addition, patient demographics, presentation, and outcomes were recorded. RESULTS: Of the 15 patients evaluated, local symptoms related to the mass were found in 11 cases at admission. The size of the mass ranged from 3.4 to 25.1 cm (mean, 11.5 cm). Nine cases were round or oval, 6 were lobulated, and 10 displaced adjacent organs. Unenhanced CT revealed a heterogeneous isodense mass in 7 cases, homogeneous isodense mass in 3 cases, and punctuated calcification in one case. On MRI, most of the lesions (6/7) were heterogeneous isointense and heterogeneous hyperintense on T1-weighted images and T2-weighted images, respectively. All tumors showed moderate to marked enhancement. Heterogeneous enhancement was revealed in 11 lesions, and 7 of these had cysts, necrosis, or hemorrhage. Early nonuniform enhancement with a radial area that proved to be a fibrous component was observed in 4 lesions, which showed progressive enhancement in the venous and delayed phase. No statistical difference in the imaging findings was observed between the histologically benign and malignant lesions. Three patients had local recurrence or metastasis at follow-up. CONCLUSION: Abdominal and pelvic SFTs commonly appeared as large, solid, well-defined, hypervascular masses with variable degrees of necrosis or cystic change that often displaced adjacent structures.

Clinical and computed tomography features of adult abdominopelvic desmoplastic small round cell tumor.

To investigate the clinical and computed tomography (CT) features of desmoplastic small round cell tumor (DSRCT), we retrospectively analyzed the clinical presentations, treatment and outcome, as well as CT manifestations of four cases of DSRCT confirmed by surgery and pathology. The CT manifestations of DSRCT were as follows: (1) multiple soft-tissue masses or diffuse peritoneal thickening in the abdomen and pelvis, with the dominant mass usually located in the pelvic cavity; (2) masses without an apparent organ-based primary site; (3) mild to moderate homogeneous or heterogeneous enhancement in solid area on enhanced CT; and (4) secondary manifestations, such as ascites, hepatic metastases, lymphadenopathy, hydronephrosis and hydroureter. The prognosis and overall survival rates were generally poor. Commonly used treatment strategies including aggressive tumor resection, polychemotherapy, and radiotherapy, showed various therapeutic effects. CT of DSRCT shows characteristic features that are helpful in diagnosis. Early discovery and complete resection, coupled with postoperative adjuvant chemotherapy, are important for prognosis of DSRCT. Whole abdominopelvic rather than locoregional radiotherapy is more effective for unresectable DSRCT.

CD40 signal regulates CXCR4 mediating ovarian carcinoma cell migration: implications for extrapelvic metastastic factors.

Ovarian carcinomas are highly invasive, especially in the peritoneal cavity. SDF-1α and its receptor, CXCR4, play a crucial role in migration of cancer cells. Here, SDF-1α directed HO8910 cell migration, but not SKOV3 cells. After being educated to express CXCR4 in vivo or by treating with sCD40L, SDF-1α reexhibited the ability of directing SKOV3 cell migration, which could be antagonized by CXCR4-neutralizing antibody. Furthermore, concomitant expression of CXCR4/CD40 in ovarian carcinoma tissues had stronger correlation with pelvic metastasis than did each alone. It is suggest that SDF-1α acts through CXCR4 to induce ovarian cancer cell migration, which could be facilitated by CD40 activation. Simultaneously examining the expression of CXCR4 and CD40 will provide valuable diagnosis of pelvic metastasis for ovarian carcinomas.

Extragonadal seminoma presenting as a large mass in the pelvic cavity without c-kit-activating mutations.

Extragonadal germ cell tumors are relatively rare tumors, which usually occur in the mediastinum or retroperitoneum. In this report, we present a case of primary seminoma arising in the pelvic cavity. A 58-year-old man with urinary retention and abdominal distension was admitted to our hospital. Computed tomography and magnetic resonance imaging demonstrated a large mass in the pelvic cavity. Histological examination of the specimens obtained by open biopsy revealed seminomatous malignant cells. Immunohistochemical studies detected vimentin, placental alkaline phosphatase and c-kit. Taking these results together with the patient's other clinical manifestations, this case was diagnosed as extragonadal seminoma without c-kit-activating mutations, and chemotherapy followed by radiation therapy was successful. Primary seminoma in the pelvic cavity is extremely rare, but should be considered a cause of pelvic mass formation.

[Inflammatory fibrosarcoma: a clinical morphological study of six cases].

The report describes the clinical and morphological characteristics of inflammatory fibrosarcoma (6). Tumor occurred in the mediastinum, small pelvis and liver in patients aged 12-64 yrs. It featured infiltrative growth. Primary tumor relapsed in 2 cases, distant metastases - 4. Four patients died from tumor progression within 7-14 months after diagnosis. Tumors consisted of neoplastic fibroblasts and lymphofibroblasts with polymorphous nuclei and high mitotic activity.

Undifferentiated pelvic adenocarcinomas: diagnostic potential of protein profiling and multivariate analysis.

BACKGROUND AND AIMS: Despite improved techniques, the determination of tumor origin in poorly differentiated adenocarcinomas still remains a challenge for the pathologist. Here we report the use of protein profiling combined with principal component analysis to improve diagnostic decision-making in tumor samples, in which standard pathologic investigations cannot present reliable results. MATERIALS AND METHODS: A poorly differentiated adenocarcinoma of unknown origin located in the pelvis, infiltrating the sigmoid colon as well as the ovary, served as a model to evaluate our proteomic approach. Firstly, we characterized the protein expression profiles from eight advanced colon and seven ovarian adenocarcinomas using two-dimensional gel electrophoresis (2-DE). Qualitative and quantitative patterns were recorded and compared to the tumor of unknown origin. Based on these protein profiles, match sets from the different tumors were created. Finally, a multivariate principal component analysis was applied to the entire 2-DE data to disclose differences in protein patterns between the different tumors. RESULTS: Over 89% of the unknown tumor sample spots could be matched with the colon standard gel, whereas only 63% of the spots could be matched with the ovarian standard. In addition, principal component analysis impressively displayed the clustering of the unknown case within the colon cancer samples, whereas this case did not cluster at all within the group of ovarian adenocarcinomas. CONCLUSION: These results show that 2-DE protein expression profiling combined with principal component analysis is a sensitive method for diagnosing undifferentiated adenocarcinomas of unknown origin. The described approach can contribute greatly to diagnostic decision-making and, with further technical improvements and a higher throughput, become a powerful tool in the armentarium of the pathologist.

Unusual presentation of an abdominoinguinal schwannoma.

Schwannoma is a rare, benign peripheral nerve sheath tumor of uncertain origin. This report describes a retroperitoneal cellular schwannoma that extended into the inguinal region. Surgical dissection of a tumor in this site requires an abdominopelvic approach. Histology revealed nodules of pale epithelioid cells separated by fascicles of spindle cells. With immunohistochemistry, no actin was seen. Neurospecific vimentin confirmed the presence of nerve cells. The tumor was completely removed, and as of 6 months later there had been no recurrence. Schwannoma are extremely difficult or even impossible to diagnose preoperatively. If clinicians are faced with an inguinal swelling or herniation and a coexisting abdominal mass, they should perhaps consider radiologic studies that better identify the origin.

[Clinicopathological and immunohistochemical analysis of gastrointestinal, urinary and perineal stromal tumors].

OBJECTIVE: To study the histogenesis and pathological characteristics of gastrointestinal stromal tumors (GIST) and GIST type stromal tumor (ST) beyond the gastrointestinal tract. METHODS: A retrospective study was carried out on leiomyoma, leiomyosarcoma and neurilemoma (46 cases in gastrointestinal tract and l3 cases in urinary tract and perineal area). 4 antibodies (CD117, CD34, SMA, S-100) were used for immunohistochemical staining. RESULTS: Among 45 cases of GIST, the positive rate of CD117 and CD34 was 93.3% and 88.9% respectively. Among 12 cases of GIST type ST beyond the gastrointestinal tract, the positive rate of CD117 and CD34 was 83.3% and 75.0% respectively. In 2 cases (1 in gastrointestinal tract) of leiomyomas, both CD117 and CD 34 were negative in tumor cells, while SMA was extensively positive. CONCLUSIONS: CD117 and CD34 positivity are the most valuable factors in diagnosing ST. Both GIST and GIST type ST beyond the gastrointestinal tract are considered originating from a proto-interstitial stem cell with disoriented differentiation.