Adnexal Involvement Research Articles

Lymphovascular space invasion and cervical stromal invasion are independent risk factors for nodal metastasis in endometrioid endometrial cancer.

The purpose of this study was to investigate the potential roles of pathological variables in the prediction of nodal metastasis in women with endometrioid endometrial cancer (EC). Women who underwent surgery for endometrioid EC between 1995 and 2012 were retrospectively reviewed. Those who underwent prior neoadjuvant chemotherapy or radiotherapy and inadequate lymphadenectomy as well as those with nonendometrioid histology, synchronous cancers, International Federation of Gynecology and Obstetrics stage IV disease, gross uterine serosal and/or gross adnexal involvement were excluded. Lymph node dissemination was defined as occurring in the following circumstances: (i) when nodal metastasis with pelvic and/or para-aortic (P/PA) lymph node dissection (LND) was performed or (ii) when there was recurrence in the P/PA lymph nodes after a negative LND or when LND was not performed. Univariate and multivariate logistic regression models were used to identify the pathological predictors of lymphatic dissemination. A total of 827 women with endometrioid EC were assessed; 516 (62.4%) of whom underwent P/PA LND and 205 (24.8%) underwent P LND. Sixty-seven (13%) women in the P/PA LND group and 5 (2.4%) in the P LND group had positive lymph nodes. Multivariate analysis confirmed cervical stromal invasion (OR 4.04, 95% CI 2.02-8.07 (P<0.001)) and lymphovascular space invasion (LVSI) (OR 110.18, 95% CI 38.43-315.87 (P<0.001)) as independent predictors of lymphatic dissemination. Cervical stromal invasion and LVSI are highly associated with LN metastasis. These markers may serve as a surrogate for nodal metastasis.

Clinical outcomes of uterine carcinosarcoma: results of 94 patients.

We aimed to determine the clinicopathologic features and identify prognostic factors of patients with uterine carcinosarcoma. A total of 94 patients with uterine carcinosarcoma who were diagnosed between January 1993 and October 2013 were included. Staging surgery consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, peritoneal cytology, and omentectomy. Staging is undertaken according to the 2009 International Federation of Gynecology and Obstetrics staging system. Kaplan-Meier survival analysis was used to determine the effects of variables on disease-free survival (DFS) and overall survival (OS). Seventy-nine patients underwent staging surgery and none of them had residual tumor after surgery. Three-year DFS and 3-year OS were 42.7% and 59.2%, respectively. In the univariate analysis, stage, presence of para-aortic metastatic lymph nodes, uterine serosal spread, positive peritoneal cytology, and extrapelvic metastases were associated with 3-year DFS and stage, presence of para-aortic metastatic lymph nodes, uterine serosal spread, positive peritoneal cytology, adnexal involvement, and extrapelvic metastases were associated with 3-year OS. Seventy-four patients received adjuvant therapy. Adjuvant therapy did not reduce recurrence or improve survival. Any of the chemotherapy regimens was not superior to the others. In the multivariate analysis, only age was an independent prognostic factor for 3-year DFS and no parameter was statistically significant for 3-year OS. Age was an independent prognostic factor for 3-year DFS. Older age was associated with poor survival. Extrauterine spread was associated with survival. The aims of surgery should be both staging and providing tumoral debulking. Prospective randomized trials are needed to better define the necessity and modality of the administered adjuvant therapy.

Preoperative thrombocytosis and poor prognostic factors in endometrial cancer.

This study aimed to evaluate the prevalence of preoperative thrombocytosis and its prognostic significance in Thai patients with endometrial cancer. We retrospectively reviewed the medical records of 238 cases who had undergone surgical staging procedures between January 2005 and December 2008. Associations between clinicopathological variables and preoperative platelet counts were analyzed using Pearson's chi square or two- tailed Fisher's exact tests. Survival analysis was performed with Kaplan-Meier estimates. Univariate and Cox- regression models were used to evaluate the prognostic impact of various factors including platelet count in terms of disease-free survival and overall survival. The mean preoperative platelet count was 315,437/μL (SD 100,167/ μL). Patients who had advanced stage, adnexal involvement, lymph node metastasis, and positive peritoneal cytology had significantly higher mean preoperative platelet counts when compared with those who had not. We found thrombocytosis (platelet count greater than 400,000/μL) in 18.1% of our patients with endometrial cancer. These had significant higher rates of advanced stage, cervical involvement, adnexal involvement, positive peritoneal cytology, and lymph node involvement than patients with a normal pretreatment platelet count. The 5-year disease-free survival and overall survival were significantly lower in patients who had thrombocytosis compared with those who had not (67.4% vs. 85.1%, p=0.001 and 86.0% vs. 94.9%, p=0.034, respectively). Thrombocytosis was shown to be a prognostic factor in the univariate but not the multivariate analysis. In conclusion, presence of thrombocytosis is not uncommon in endometrial cancer and may reflect unfavorable prognostic factors but its prognostic impact on survival needs to be clarified in further studies.

A Case of Extramammary Paget's Disease Resistant to Photodynamic Therapy and Surgery Successfully Treated with Radiotherapy.

Dear Editor: Although surgery is widely accepted as the first-line treatment for extramammary Paget's disease (EMPD), it cannot always be accomplished due to its frequent involvement of areas with important function1. Nonsurgical treatments including radiotherapy (RTx) and photodynamic therapy (PDT) are considered in such cases. We report a case of EMPD refractory to PDT and surgery that was successfully treated with RTx. A 68-year-old man presented with a well-defined erythematous patch with ulceration on the left side of scrotum, which enlarged during the last 7 months (Fig. 1A). Skin biopsy revealed numerous Paget cells (Fig. 2). Possible accompanying internal neoplasms were discounted through multiple means, ranging from physical examination to positron emission tomography/computed tomography. Diagnosed as localized EMPD, the patient was primarily treated with PDT because he strongly requested preservation of his genitourinary functions. Methyl aminolevulinate cream (Metvix; Galderma, Fortworth, TX, USA) was applied occlusively and was maintained for 3 h. The lesion was then irradiated with a 630-nm light-emitting diode (Aktilite CL128; Photocure, Oslo, Norway). After two sessions, the patient showed a partial response and underwent local excision. He was treated with 15 sessions of PDT for possible remnants. As Paget cells were still seen on follow-up biopsy of the surgical margin, he underwent a three-stage Mohs surgery and received 11 additional sessions of PDT. Nonetheless, the lesion persisted clinically. We referred him to the radiation-oncology clinic. Radiation was administered by using an electron beam of 6 MeV, at 200~250 cGy per day, 4 days a week, until a total dose of 37 Gy was reached. He received subsequent RTx with a total dose of 30 Gy in same manner. The lesion disappeared completely. After 18 months, the patient revisited our clinic with an erythematous patch on the scrotum (Fig. 1B). Biopsy only revealed telangiectatic dermal vessels. Fig. 1 (A) Patient image at initial visit. (B) The patient revisited our clinic suspecting of recurrence. The biopsy of skin lesion did not show any tumor cells. Fig. 2 Skin biopsy showing acanthotic epidermis with numerous Paget cells of large nucleus and eosinophilic cytoplasm (H&E, ×200). A systematic review of clinical studies examining the use of PDT for EMPD showed that of 133 EMPD lesions, 77 exhibited complete response and 52 exhibited partial response with satisfactory cosmetic outcome in all patients2. However, the durability of this response remains unclear, as the follow-up periods were typically less than a year2. In a long-term follow-up study of EMPD in situ for 24 months, the recurrence rate was 50%. The authors stated that PDT should be recommended only for cases of scrotal lesions <4 cm in diameter3. Larger lesions showed an unfavorable response presumably because of the denser infiltration of Paget cells and more adnexal involvement, followed by disproportionate protoporphyrin IX accumulation in the glands resulting in photodynamic oxygen depletion. In the present case, the lesion was much larger than 4 cm, which may have been responsible for the ineffectiveness of PDT. The optimal RTx dose is not standardized; however, a total of 40~50 Gy has been considered suitable for primary treatment4. The lesion of our case was refractory to other therapies; hence, a higher dose of 67 Gy was chosen. In conclusion, EMPD lesions resistant to PDT and surgery may be significantly resolved with RTx; thus, it should be considered a treatment option in cases of repeatedly unsuccessful PDT and surgery.

Postoperative radiotherapy for endometrial cancer: treatment results and prognostic factors

Introduction and Purpose: In this study, we aim to investigate the effects of the prognostic factors related to tumour, treatment, local and regional controls, overall survival, and disease free survival in postoperative radiotherapy patients. Materials and Methods: Sixty-one patients admitted to suffering from adenocarcinom of endometrium were analyzed retrospectively following surgical operation, adjuvant radiotherapy, and brachytherapy. We evaluated the patients in trems of age, tumour differentiations, tumour stage, lymphovascular invasion, serosal invasion, myometrial invasion, endocervical invasion, adnex involvement, lymph node involvement, menopausal age, hypertension, diabetes mellitus, smoking history, parity, hormone replacement therapy, chemotherapy process, vaginal brachitherapy, the type and doses of radiotherapy and local relapses. Throughout our research, we studied how overall survival and disease-free survival are influenced by factors like age, stage, tumour differentiation, histological type, lymph node involvement, lymphovascular invasion (LVI), endocervical invasion, serosal invasion, menopausal age, hypertension, diabetes mellitus, smoking history, parity, hormone replacement therapy (HRT), operation type, depth of myometrial invasion, and adnexal involvement. Results: Fifty three patiens (87%) were exposed to total abdominal hysterectomy+bilateral saphingo oohporectomy+bilateral pelvic lymp node dissection (TAH+BSO+BPLND), while 8 patients (13%) were exposed to TAH-BSO. Thirty patients were treated by conventional methods, 23 patients were treated by conformal methods. Eight patients were treated only by brachytherapy. The five-year overall survival rate was 80.3% and disease-free survival rate was found to be 77%. Two year overall survival rate was 93.4% and disease-free survival rate was 85.2%. It was noticed that serosal invasion (p=0.034) affect overall survival.

Isolated eye lid Cysticercosis: Report of a rare case with review of literature

Cysticercosis is a parasitic infection caused by larval form of Taenia solium. Humans become the intermediate hosts for this parasite when the eggs are consumed through contaminated food and water. It is endemic in India. Approximately 50 million people worldwide are infected with the Taeniasis/Cysticercosis complex and 50,000 succumb to death annually. The commonest site of cysticercosis is central nervous system in humans followed by muscles, eyes and subcutaneous tissue. Ocular or adnexal involvement occurs in 13-46% and 1.8-4.5% of the Western and Indian patients suffering from cysticercosis, the commonest ophthalmic site being subretinal space. The anterior segment is the commonest location in Indians where as in Western population it is posterior. The orbit is involved in only 1% of the cases. Only a handful of cases of eyelid cysticercosis have been reported in the past. We report a rare case of isolated eyelid cysticercosis in a young girl who presented with an asymptomatic slowly growing painless mass in the right eyelid. Key words: Cysticercosis, eyelid, Histopathology

Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin.

Progression from actinic keratosis (AK) to invasive squamous cell carcinoma (iSCC) of the skin is thought to occur after the development of full thickness epidermal neoplasia, as in the classic pathway of cervical cancer. Nevertheless, cutaneous iSCC may also directly arise from a proliferation of atypical basaloid cells limited mostly to the epidermal basal layer (AK I), akin to what happens in the 'differentiated pathway' of iSCC of the vulva, oral cavity and other locations. To evaluate the prevalence of classic and differentiated pathways in the development of cutaneous iSCC. The epidermis adjacent to and overlying iSCC, assumed to be representative of pre-existing lesions, was histologically studied in 196 skin biopsy specimens showing iSCC. AK I, AK II and AK III lesions overlying iSCC were present in 63.8%, 17.9% and 18.4% of cases respectively. The corresponding percentages in the epidermis adjacent to iSCC were 77.9%, 6.6% and 8.3% respectively (stage could not be assessed in 8.1% of cases). Focal epidermal ulceration overlying iSCC was seen in 32% of AK I, 28.6% of AK II and 33.3% of AK III instances. Adnexal involvement by atypical keratinocytes (proliferative AK) was present more frequently in cases with overlying AK I (39/125, 31.2%) than with AK II (8/35, 22.9%) and AKII I (5/36, 13.9%). Direct invasion from proliferating basaloid atypical keratinocytes limited to the epidermal basal layer (AK I), known as the differentiated pathway, was the most common form of progression to cutaneous iSCC in our series. On the other hand, stepwise progression from AK I to AK II and AK III (classic pathway) was seen to be operative in a substantial proportion of iSCC cases. All AK lesions, irrespective of intraepidermal neoplasia thickness, are therefore potentially invasive and tumour advance along adnexal structures might facilitate iSCC development from AK I lesions.

Undifferentiated uterine carcinoma: Analysis of eighteen cases

Analysis of the surgicopathological characteristics and clinical follow-up of patients with undifferentiated uterine carcinoma (UUC) was conducted. A total of 18 cases operated between January 1993 and December 2013 were included. Among 1,690 patients with endometrial cancer, 18 patients (1.1%) had UUC. Lymph node involvement was detected in 70.6%; depth of myometrial invasion was ≥ 0.5 in 55.6%; lymphovascular space invasion was detected in 99.3%; cervical stromal invasion was positive in 27.8%; omental and adnexal involvement were detected in 11.8% and 38.9%, respectively. The median follow-up time of the 12 patients evaluated in the survival analysis was 66 months. In the follow-up period, recurrence or progression during adjuvant therapy were observed in four patients (33.3%) and two patients (16.6%) died of the disease. UUC manifests as an aggressive tumour. In conclusion, a high rate of survival could be achieved with complete staging surgery, including an extensive lymphadenectomy with the contribution of adjuvant therapy.

Ocular involvement and visual outcome of herpes zoster ophthalmicus: review of 45 patients from Tunisia, North Africa.

BackgroundOcular complications of herpes zoster ophthalmicus (HZO) may lead to substantial visual impairment. The purpose of this study was to characterize and analyze ocular involvement and visual outcome of HZO in patients from Tunisia, North Africa. This study is a retrospective chart review of 51 eyes of 45 patients with HZO.ResultsMean age was 44.5 years. Thirty patients (66.7%) were aged over 50 years. Twenty-four patients (53.3%) were male and 21 patients were female (46.7%). There was no statistically significant difference in gender distribution. Initial mean best corrected visual acuity (BCVA) was 20/50. Ocular manifestations included adnexal involvement (58.8%), keratitis (31.4%), keratouveitis (31.4%), isolated anterior uveitis (AU) (29.4%), intraocular pressure elevation (23.5%), oculomotor nerve palsy (5.8%), and optic neuritis (1.9%). Isolated AU (p < 0.001), isolated keratitis (p = 0.001), and intraocular pressure elevation (p = 0.013) were more likely to be concomitant to HZO active skin disease, while keratouveitis occurred more likely more than 1 month after HZO eruption (p < 0.001). AU and keratouveitis were more likely to be associated with age ≥ 50 years (p = 0.001 and p = 0.02, respectively). Ocular complications included neurotrophic keratopathy (1.9%), corneal opacity (5.9%), secondary glaucoma (7.8%), optic atrophy (1.9%), and postherpetic neuralgia (13.3%). Mean follow-up was 12 months. Mean final BCVA was 20/32; it was ≥ 20/40 in 78.4% of the eyes.ConclusionsOur study provided epidemiologic and clinical data of HZO in a Tunisian population. AU and keratitis were the most common ocular complications. Neurotrophic keratopathy was scarce. The overall visual outcome is good, with about three quarters of the treated patients maintaining VA of 20/40 or better.

Lymphovascular Space Invasion Is an Important Prognostic Factor for Lymph Node Metastases in Endometrioid Endometrial Cancer

Lymphovascular Space Invasion Is an Important Prognostic Factor for Lymph Node Metastases in Endometrioid Endometrial Cancer

A Phase 1/2 Study of the Angiogenesis Inhibitor Sorafenib in Cervical Cancer Patients Treated With Radiation Therapy

randomized trials have shown no survival benefit. However, identification of lymph node (LN)-positive women is important for directing adjuvant therapy. We developed a nomogram based on pathologic characteristics from surgical hysterectomy specimens to predict for LN metastasis. Materials/Methods: We retrospectively examined pathological data from all hysterectomies with LN sampling performed for endometrioid endometrial adenocarcinoma at our institution. A multivariate logistic regression analysis of selected features was performed, and a nomogram to predict LN metastasis was constructed. Results: From 1996 to 2013, 301 patients underwent hysterectomy with LN sampling for endometrial cancer. Surgical staging revealed the following staging distribution: FIGO IA (n Z 163), FIGO IB (n Z 57), FIGO II (n Z 22), FIGO IIIA-B (n Z 17), FIGO IIIC (n Z 33), and FIGO IV (n Z 9). One hundred five patients had grade 1, 123 patients had grade 2, and 73 patients had grade 3 tumors. No patient had prior treatment for endometrial cancer. While pelvic nodes were sampled in all cases, paraortic nodes were sampled in 135 cases. Median number of LNs removed was 13 (range, 1-72). On univariate analysis, tumor size 4 cm, grade, lymphovascular space involvement (LVSI), cervical stromal involvement, adnexal involvement, serosal involvement, positive pelvic washings, parametrial involvement, > one-half myometrial invasion, and number of LNs removed all significantly predicted for LN involvement. Age and ER/PR status did not. In a multivariate model, LVSI (p Z 0.0003, OR Z 6.5), > one-half myometrial invasion (p Z 0.04, OR Z 2.7), and cervical stromal involvement (p Z 0.003, OR Z 1.3) remained significant predictors of LN involvement, while tumor size 4 cm was borderline significant (p Z 0.07, OR Z 2.17). In particular, grade was no longer significant (p Z 0.56) when considered together with other factors. We constructed a prognostic nomogram (AUC 0.87), including LVSI, myometrial invasion, cervical stromal involvement, and tumor size. Of these factors, LVSI was most predictive of LN involvement, with a standardized coefficient of 49% in our model. Of 100 patients who had LVSI in this study, 30% had LN metastases. Conclusions: Studies have reported factors such as tumor size, grade, and depth of invasion as predictive of LN metastases, which we confirm. However, when looking at these factors together, LVSI was most predictive of LN involvement, followed by myometrial invasion and cervical stromal involvement, regardless of tumor grade. LVSI should be one of the main prognostic factors used to help direct adjuvant therapy in patients without LN surgery. Author Disclosure: E. Pollom: None. C. Conklin: None. R. Von Eyben: None. A. Folkins: None. E. Kidd: None.

Lack of Relation of Survivin Gene Expression with Survival and Surgical Prognostic Factors in Endometrial Carcinoma Patients

The relation of survivin gene expression to survival and surgical prognostic factors in the patients with endometrial carcinoma is unclear. In this study, 62 cases who were operated due to endometrial carcinoma were investigated between 2003 and 2011 in the the gynecological oncology clinic of Female Disease Training and Investigation Hospital of Etlik Zubeyde, Hanim, Turkey. Clinical and surgical prognostic factors were investigated by screening the records of these cases. With the standard streptavidin-biotin immune peroxidase method, cytoplasmic and nuclear expression of survivin was investigated in sections with specific antibodies (1:100, diagnostic Bio Systems, USA) primer. The aim was to elucidate any relation between survivin expression and defined prognostic factors and survival. There was no statistically significant relationship between cytoplasmic and nuclear indexes identified for survivin and age, body mass index, the levels of preoperative hemoglobin, platelet and Ca 125, stage, grade, lymph node meastasis, the number of metastatical lymph nodes (total, paraaortic and pelvic), myometrial invasion, serosal invasion, adnexal involvement, the presence of acid in the first diagnosis, the involvement of omentum, the adjuvant treatment application of the cases, the presence of recurrence and rate of mortality (p>0.05). Statistical significance was noted for the presence of advanced stage lymph node metastasis (pelvic, paraaortic, pelvic and paraaortic), serosal involvement, positive cytology, lymph vascular space invasion, intra abdominal metastasis, and omentum involvement. When investigated the relation between cytoplasmic and nuclear survivin indexes and total survival, the result was not statistically significant (p>0.05). In our study, there was no statistically significant relationship between the rates of cytoplasmic and nuclear survivin expression with identified prognostic factors and total or non-disease survival.

The outcome and efficacy of adjuvant chemotherapy alone in patients with stage IIIA endometrial carcinoma with solitary adnexal involvement: A retrospective single-institution study

ObjectivesThe appropriate adjuvant therapy for patients with endometrial carcinoma with solitary adnexal involvement is unclear. We conducted a retrospective single-institution study to evaluate the outcome and efficacy of adjuvant chemotherapy alone in this population. MethodsAll patients with endometrial carcinoma who received primary surgical treatment between January 1999 and May 2010 were reviewed. The patients who were diagnosed with stage IIIA disease based only on isolated adnexal involvement and treated with surgical procedures followed by adjuvant chemotherapy alone were included. Demographic, clinicopathologic, treatment and outcome data were collected. Recurrence and survival were analyzed. ResultsAmong 1453 reviewed patients, 67 patients were identified. The median age was 48years. All patients were treated with platinum-based adjuvant chemotherapy, with the majority (36/67, 53.7%) receiving paclitaxel plus carboplatin. The total number of cycles of chemotherapy administered was 305 (median four cycles/person). Most of the chemotherapy related toxicities were mild or moderate. The median follow-up time was 76months. Eight patients experienced recurrence. The majority of initial relapses were distant (7/8, 87.5%), characterized by liver metastases (3/8, 37.5%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 89.6% and 91.9%, respectively. Multivariate analysis confirmed that grade 3 tumor was an independent predictor of worse DFS and OS (HR=5.19, P=0.048; HR=6.55, P=0.037, respectively). ConclusionPatients with stage IIIA endometrial carcinoma with solitary adnexal involvement have favorable outcomes. Adjuvant chemotherapy alone may be effective and feasible for these patients.

CD44 expression in curettage and postoperative specimens of endometrial cancer.

BackgroundAdhesive molecules like CD44 are well defined key players in the metastatic cascade in many cancers, including endometrial cancer. They could play a role of markers of invasion, metastasis and prognostic factors.Aim of the studyThe aim of the study is to assess a possible role of the CD44 as a marker of invasion in endometrial cancer, both at the moment of preoperative workup and final staging.Materials and methodsAvailable for analysis were archival specimens of 51 patients who had underwent curettage and surgery between 2002 and 2007. An immunohistochemical study for CD44 expression was performed in curettage and postoperative specimens. Normal endometrium of 20 randomly chosen patients was used as a control group.ResultsIn endometrial cancer the expression of CD44 was significantly more intensive than in normal endometrium. In postoperative specimens, the CD44 expression was weaker in serous than in endometrioid cancer. There was no significant correlation between the adhesion molecule expression and clinicopathological features: grade,depth of invasion, cervical involvement, serosal and adnexal involvement, lymph-vascular space involvement, lymph node and distant metastases nor FIGO stage.ConclusionsAn increased expression of CD44 in endometrial cancer suggests its possible role in pathogenesis of this disease, however, it doesn’t seem to be crucial. Different expression of the CD44 in endometrioid and papillary-serous type may reflect different pathogenesis of these types of cancer. No statistically proved relation between the investigated molecule expression and clinicopathological parameters suggests scepticism about its use in diagnostic process of endometrial cancer.

What is the importance of omental metastasis in patients with endometrial cancer?

To identify surgico-pathologic factors, survival, and the factors determining survival in patients with omental metastasis from endometrial cancer. Patients with endometrial cancer operated on between 1993-2012 in our hospital and who had omental metastases were included. Patients with either uterine sarcoma or synchronous tumors were excluded. Omentectomy was performed in 811 patients with endometrial cancer, and omental metastasis was found in 48 (5.9%) patients. Tumor type was endometrioid cancer in 26 patients. Omental metastasis was macroscopic and microscopic in 60% and 40% of the patients, respectively. Total omentectomy increased the chance of detection of the microscopic metastases. Among the patients with omental metastasis, 68.8% had positive peritoneal cytology, 66.7% had adnexal involvement, 60.5% had metastases in the lymph nodes, 47.9% had cervical involvement, and 29.2% had serosal involvement; 43.8% of these patients had intra-abdominal spread beyond the omentum, adnexa, and peritoneal cytology. Two-year disease-free survival (DFS) was 28.2%, and 2-y overall survival (OS) was 40%. The depth of myometrial invasion, grade, cytology, and status of pelvic lymph nodes affected 2-y DFS, while cervical invasion and cytology affected 2-y OS. Omental metastasis in endometrial cancer means poor prognosis, and two-thirds of these patients are lost at the end of the second year. Although total omentectomy increases the chance of the detection of micrometastases, its effect on survival is controversial. New treatment modalities are necessary in this patient group.

Mucinous differentiation does not impact stage or risk of recurrence among patients with grade 1, endometrioid type, endometrial carcinoma

ObjectiveTo evaluate whether the presence of mucinous differentiation influences histopathologic findings, stage distribution, or rate of recurrence among women with grade 1, endometrioid type, endometrial carcinoma. MethodsThis was a retrospective cohort study of all patients with grade 1, endometrioid type, endometrial carcinoma between January 2005 and December 2012. Patients were separated by the presence or absence of mucinous differentiation and then compared. ResultsOf 655 patients, mucinous differentiation was present in 137 (20.9%) and absent in 518 (79.1%) patients. Compared to the group without mucinous differentiation, the group containing mucinous differentiation was older at diagnosis (mean: 61.1 vs. 58.5years, OR, 95% CI; 1.03, 1.01–1.05) and more likely to have myometrial invasion (61.3% vs. 51.5%, OR, 95% CI; 1.49, 1.01–2.19). Additional histopathologic findings including: tumor size, cervical stromal invasion, adnexal involvement, LVI and/or the presence of positive lymph nodes were similar between groups. Mucinous differentiation did not affect stage distribution, as most patients were stage 1A (85.4% vs. 86.3%). The median PFS for the entire group has yet to be reached. The mean PFS for the entire study sample was 94.7months. There was no difference in mean PFS when comparing the group with mucinous differentiation to the group without mucinous differentiation (98 vs. 93.4months, p=0.07). ConclusionsIn the setting of grade 1, endometrioid type, endometrial carcinoma, mucinous differentiation is more common in older patients and is associated with an increased likelihood of myometrial invasion. However, stage distribution and risk of recurrence are not affected.

Granulomatous Dacryoadenitis in Regional Enteritis (Crohn Disease)

To evaluate the clinical and immunopathologic features of 2 patients with bilateral dacryoadenitis associated with regional enteritis. Retrospective, clinicopathologic study. Clinical records, photographs, and imaging studies were reviewed and microscopic sections of lacrimal gland biopsy samples were critically re-evaluated. The microscopic slides were stained with hematoxylin and eosin, special stains for organisms, and a range of immunohistochemical biomarkers, including CD3, CD4, CD5, CD8, CD20, CD68, CD138, CD1a, and immunoglobulins Ig G, IgG4, and IgA. Both patients were young women with a well-established diagnosis of regional enteritis. Histopathologic examination of biopsy samples disclosed moderate intraparenchymal fibrosis and lymphoplasmacytic infiltrates without lymphoid follicles. Small to medium intraparenchymal, noncaseating granulomas lacking multinucleated giant cells and, in 1 patient, CD68-positive and CD1a-negative palisading granulomas in widened interlobular fibrous septa were detected. Vasculitis and IgG4 plasma cells were not observed. Additional immunohistochemical studies revealed that CD8T lymphocytes (suppressor or cytotoxic subset) predominated over CD4-positive T lymphocytes (helper cells) surrounding the necrobiotic foci and were intermixed with the CD68-positive histiocytes in the absence of CD20 B lymphocytes. Special stains for organisms demonstrated negative results. Dacryoadenitis is the rarest form of ocular adnexal involvement in regional enteritis, which affects the orbit far more frequently than ulcerative colitis. It is a granulomatous process with the possibility of palisading necrobiotic foci. In contrast, ulcerative colitis causes an interstitial lymphocytic and nongranulomatous myositis. Sarcoidosis, Wegener granulomatosis, and pseudorheumatoid nodules must be ruled out. Treatment options entail a wide variety of agents with selection based on empirical considerations and tailored to the patient's symptoms.

Quantifying the risk of recurrence and death in stage III (FIGO 2009) endometrial cancer

ObjectiveAdvanced endometrial cancer patients comprise a heterogeneous group. This study assessed the association of clinicopathological factors with relapse and death from endometrial cancer. MethodsEligible patients were treated for stage III (FIGO 2009) endometrial adenocarcinoma, had peritoneal cytology performed, and had no gross residual disease post-operatively. ResultsOf 192 patients, 59% were ≥60years old, 48% had ≥50% myometrial invasion, 71% lymphovascular invasion, 25% cervical stromal invasion, 37% adnexal involvement, and 23% positive peritoneal cytology. High-grade histology (serous, clear cell, undifferentiated, or grade 3 endometrioid) was present in 45%. Pelvic lymphadenectomy was performed in 93% and para-aortic lymphadenectomy in 73%. Adjuvant chemotherapy and/or radiation therapy was administered to 93%. At a median follow-up of 42months, the 5-year rate of relapse was 37% and of death from endometrial cancer was 30%. On multivariate analysis, both outcomes were associated with high-grade histology, positive peritoneal cytology, and deep myometrial invasion (p≤0.04). The cohort was divided into subgroups of patients with 0 (n=46), 1 (n=83), or ≥2 (n=63) of these high-risk characteristics. The 5-year relapse rate for patients with 0 risk factors was 13%, 1 risk factor was 27%, and ≥2 risk factors was 62% (p<0.001). The corresponding 5-year rates of death from endometrial cancer were 11%, 20%, and 56%, respectively (p<0.001). ConclusionsStratification of stage III endometrial cancer according to high-grade histology, positive peritoneal cytology, and deep myometrial invasion is useful for prognostication and may grant insight into the optimal treatment for specific subgroups of patients.

Angiolymphoid Hyperplasia With Eosinophilia of the Orbit and Ocular Adnexa

To report the clinical and histopathologic findings of ocular adnexal angiolymphoid hyperplasia with eosinophilia, an unusual but often misdiagnosed benign disorder. The ophthalmologic findings of angiolymphoid hyperplasia with eosinophilia with ocular adnexal involvement are variable and include eyelid swelling, ptosis, proptosis, and loss of vision. Imaging studies typically reveal a well-circumscribed mass in the orbit. The condition may resemble other diseases that involve the orbit and ocular adnexal tissue, such as lymphoma, hemangioma, sarcoidosis, and dermoid cyst. Histopathologic analysis reveals marked vascular proliferation with an accompanying inflammation composed of numerous eosinophils, lymphocytes, and plasma cells. Angiolymphoid hyperplasia with eosinophilia is a rare disease that can affect the ocular adnexal tissue. The clinical presentation is often nonspecific; therefore, histopathologic studies are essential for diagnosis and subsequent management of this benign condition.

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: A single institution study of 458 patients

ObjectiveThe aim of this study is to determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer. MethodsWe performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hysterectomy (TAH) or minimally invasive hysterectomy (MIH) with use of a disposable uterine manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy at a single academic institution between 2002 and 2012. Exclusion criteria were pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and conversion to laparotomy. Multivariate logistic regression models to determine if type of hysterectomy predicts either LVSI or presence of abnormal cytology were controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal involvement. ResultsLVSI was identified in 39/214 (18%) MIH and 44/242 (18%) TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%) TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241 (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a significant predictor of either LVSI (p=0.29) or presence of malignant washings (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03). ConclusionMinimally invasive hysterectomy with use of a uterine manipulator for endometrial cancer is not associated with LVSI or malignant cytology. Algorithms that better determine the etiology and implications of inconclusive or atypical pelvic cytology are needed to inform the possible additional risk associated with a minimally invasive approach to endometrial cancer.