Omalizumab for refractory chronic spontaneous urticaria during concurrent immunomodulatory therapy for multiple sclerosis.

SUMMARY: Data derived from previous clinical trials and real-life studies have shown that omalizumab may represent an effective third-line treatment option for patients with chronic spontaneous urticaria (CSU) refractory to standard antihistamine treatment. Nevertheless, the safety and efficacy of omalizumab treatment for CSU, when administered concurrently with other immunomodulatory agents remains largely unknown. We herein present the case of a female patient with relapsing-remitting multiple sclerosis (RRMS), under treatment with interferon beta-1a, azathioprine and gabapentin, who was successfully treated with omalizumab for refractory CSU. To the best of our knowledge, this is the first reported case attesting to the safety and efficacy of omalizumab for CSU when administered concurrently with other immunomodulatory agents.

Successful rapid desensitization to glatiramer acetate in a patient with multiple sclerosis

No disponible

Fine-needle aspiration cytology of primary renal angiosarcoma with histopathologic and immunocytochemical correlation: a case report.

Primary renal angiosarcoma is an extremely rare neoplasm, with fewer than 28 cases reported thus far in the English literature. We report for the first time the cytomorphology and immunocytochemistry of this tumor in liquid-based (ThinPrep) fine-needle aspiration (FNA) samples in correlation with the conventional cytologic and histopathologic findings. Conventional smears showed pleomorphic tumor cells focally arranged in structures suggesting anastomosing vascular channels, while ThinPrep smears were less cellular with fewer and smaller tumor cells arranged in clusters or rosette-like formations. Immunocytochemical staining demonstrated positive results for vimentin, CD31, and CD34 and negative staining for epithelial markers, thus supporting the diagnosis of a mesenchymal tumor of vascular origin. The diagnosis of primary renal angiosarcoma was established after histopathologic evaluation of a metastatic liver nodule. The cytological differential diagnosis of this neoplasm and the utility of the ThinPrep method as a diagnostic adjunct to conventional FNA cytology are further discussed.

"Immunocytochemical expression of P53, PTEN, FAS (CD95), P16INK4A and HPV L1 major capsid proteins in ThinPrep cervical samples with squamous intraepithelial lesions".

The aim of this study was to further investigate the immunocytochemical expression of p53, PTEN, Fas, p16, and HPV L1 capsid proteins in cervical smears with low and high grade squamous intraepithelial lesions (LSIL and HSIL, respectively). A total of 92 ThinPrep cervical samples, comprising 11 cases of HSIL, 61 cases of LSIL, and 20 negative cases were studied by immunocytochemical methods. The results obtained in LSIL cases were correlated with the available follow up data. Abnormal p53, PTEN, or Fas expression was found in a subset of HSIL cases, while positive expression for p16 was significantly associated with the diagnosis of HSIL (P < 0.0001, P = 0.001, P < 0.0001, and P < 0.0001, respectively). Among cases positive for p16 expression, the staining pattern was weak in 88.9% of LSIL cases and strong in 80% of HSIL cases (P < 0.0001). The p16 negative/L1 positive and p16 positive/L1 negative staining patterns were significantly associated with the presence of LSIL and HSIL, respectively (P < 0.0001). None of these markers had a significant prognostic value in LSIL cases (P > 0.05). Our results suggest that loss of PTEN or Fas expression and p53 overexpression may be involved in the process of neoplastic transformation of the cervical epithelium. Furthermore, negative or weak immunocytochemical staining for p16 in a Pap smear may strongly argue against the presence of a high grade lesion, while the combined p16/L1 staining pattern may be useful as a diagnostic adjunct for differentiating between LSIL and HSIL.

Autopsy findings in fetuses with cystic hygroma: a literature review and our center's experience.

PURPOSE OF INVESTIGATION: To report our experience of autopsied cases of fetal cystic hygroma (CH) and discuss the role of fetal autopsy in genetic counseling. METHODS: A review of autopsy reports at our institution revealed 18 cases of fetal CH over a 10-year period (from 2000 to 2010). The clinical data, results of cytogenetic analysis and prenatal ultrasound findings were also retrieved and compared to the autopsy findings. RESULTS: Fetal death was due to intrauterine death in eight cases, therapeutic abortion in eight cases and spontaneous abortion in two cases. Cytogenetic analysis was available in 12 cases, and the results showed an abnormal karyotype in seven cases (5 cases of Turner syndrome and 2 cases of trisomy 21). The mean size of CH was 5.4 cm. Other malformations or findings suggestive of the cause of fetal death were diagnosed in 10/18 cases (55.6%). The most common autopsy findings were hydrops and central nervous system anomalies. The autopsy findings were in agreement with the prenatal ultrasound findings in 13/18 cases (72.2%), while in five cases (27.8%) additional findings were detected during autopsy. The most common placental abnormalities were infarcts and calcifications. CONCLUSION: In addition to prenatal diagnostic studies, fetal autopsy and pathologic examination of fetal and placental tissues may help to establish the exact cause of death and disclose important information as to the presence of various fetal malformations or placental abnormalities.

Additional slides from residual ThinPrep Pap tests: Of potential diagnostic benefit in equivocal cases?

The aim of this study was to further evaluate the diagnostic significance of additional slides prepared from residual ThinPrep (TP) Pap Tests. Up to 10 repeat slides were prepared from 105 residual TP cervical samples. All additional slides were evaluated for the presence of diagnostic elements which were not found on the primary TP slide. After the evaluation of the repeat slides, an upgraded diagnosis was noted in 15 cases (14.3%). The reclassified cases included: three negative cases reclassified as two ASC-US and as one LSIL, seven cases of ASC-US reclassified as six LSIL and as one HSIL, and five cases of LSIL reclassified as HSIL. The highest rate (7/15 cases, 46.7%) of cases with an upgraded diagnosis was noted in the ASC-US diagnostic category. Our results suggest that repeat processing of residual TP cervical samples may represent an adjunctive diagnostic tool for a more accurate classification of ASC-US cases. Nevertheless, the practical value of this approach seems to be limited by its significant cost and its uncertain effectiveness.

Epithelial ovarian tumors in adolescents: a retrospective pathologic study and a critical review of the literature.

OBJECTIVES: The aim of this study was to further evaluate the pathologic features of epithelial ovarian neoplasms and their relative frequency among all ovarian tumors in the adolescent population. DESIGN: We conducted a retrospective pathologic study of all cases of epithelial ovarian neoplasms in adolescents (aged 11-19 years) diagnosed in the pathology laboratory of our hospital over the past 25 years. RESULTS: A total of 86 ovarian tumors were identified, including 23 epithelium-derived ovarian neoplasms (26.7%), 53 germ cell tumors (61.6%), 9 sex-cord stromal tumors (10.5%) and 1 benign Brenner tumor (1.2%). Most cases of epithelial tumors were found in patients 17 years of age or older (14/23 cases, 60.9%). All tumors were unilateral, and their size ranged from 2.5-21 cm (mean 11.7 cm). Epithelial tumors were further histologically subtyped into 21 benign cystadenomas (14 serous and 7 mucinous) and 2 mucinous borderline tumors. CONCLUSIONS: A relatively high frequency of epithelial ovarian neoplasms among all ovarian tumors in a purely adolescent population was found in our study. Age-related selection bias may account at least in part for the discrepancy between our data and most previous reports. The most common subtype of epithelial ovarian tumor in our series was the benign serous cystadenoma.

Repeat processing of residual ThinPrep Pap tests: sampling of the vial may not be invariably homogeneous.

OBJECTIVE: To re-evaluate the reproducibility of additional slides prepared from residual cervical ThinPrep (TP) samples. STUDY DESIGN: Sixty paired specimens (conventional smears and direct-to-vial TP) were studied. Up to 10 additional slides were prepared from each TP vial. All slides were reviewed for adequacy of material, presence of abnormal cells and presence of normal flora or other pathogens. The additional TP slides were further evaluated for the presence of diagnostic elements which were not found on the conventional smear and primary TP slide. RESULTS: Abnormal cells found on the primary TP slide were also identified on all additional slides in 48/50 cases (96%) with squamous cell lesions. The distribution of material on TP slides was evaluated as homogenous in 51 cases (85%) and as non-homogenous in 9 (15%). Using the primary slides (conventional smear and TP) as a reference, additional diagnostic cells upgrading the cytologic diagnosis were found on the repeat slides in 7 cases (11.7%) and fungi consistent with Candida in 3 (5%). CONCLUSION: Repeat processing of residual cervical TP samples may not be an invariably reproducible procedure and the first slide may not be necessarily representative of the specimen as a whole. Nevertheless, both primary and repeat TP slides seem to be extremely effective in detecting a lesion (regardless of grade) in abnormal cases. The exact impact of non-homogeneous sampling of the vial on the diagnostic accuracy of the TP method should be further investigated.

Granulosa cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 21 cases.

PURPOSE: To further study the clinicopathologic and immunohistochemical features of ovarian granulosa cell tumors (GCTs). METHODS: We retrospectively studied all cases of GCTs diagnosed in our laboratory over the last 10-year period. Immunohistochemistry for inhibin, vimentin, cytokeratin, Ki-67 and p53 was performed on archival paraffin blocks. Pathologic and immunohistochemical findings were correlated with the clinical records of the patients. RESULTS: Twenty-one cases (15 of the adult and 6 of the juvenile type) were retrieved. All patients were FIGO Stage I at the time of diagnosis. Recurrent disease was detected in four patients (19%) during a median follow-up of 36 months (range 2-26 years). Pathology revealed a concomitant theca-cell component in three cases, a Sertoli-Leydig component in one case, and a thecoma in one case. Archival tissue material was available in 12 cases. Immunohistochemistry was positive for: beta-inhibin in 12/12 cases (100%), vimentin in 11/12 cases (91.7%), cytokeratin in 3/12 cases (25%), CD34 in 0 cases (0%), and p53 in 2/12 cases (16.7%). The Ki-67 index was < 5% in 12/12 cases (100%). No significant correlations were observed between the pathologic and immunohistochemical parameters examined and the clinical outcome. CONCLUSIONS: Despite the relatively indolent nature and favorable prognosis of most GCTs, late recurrences are not a rare event even in Stage I patients, necessitating a close and long-term follow-up. The identification of novel prognostic markers, in addition to our traditional staging parameters such as clinical staging, is needed in order to more accurately predict probabilities of recurrence in these patients.

Carcinosarcomas of the uterus and ovary: a clinicopathologic and immunohistochemical study of 11 cases.

PURPOSE: To further study the clinicopathologic features of carcinosarcomas of the uterus and ovary. METHODS: We retrospectively studied all cases of uterine and ovarian carcinosarcomas diagnosed in our laboratory over the last 5-year period. The pathologic and immunohistochemical findings were correlated with the clinical records of the patients. RESULTS: Eleven cases were retrieved . The commonest presenting symptom was vaginal bleeding (9 cases, 81.8%). Most patients (8 cases, 72.7%) were submitted to total abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy was administered to all of them. In the majority of cases the tumor was located in the uterine corpus (7 cases, 63.6%), followed by the ovary (4 cases, 36.4%). The tumor was homologous in ten cases (90.9%) and heterologous in one case (9.1%). Most of our patients (6 cases, 54.6%) were diagnosed at an advanced stage (FIGO Stage III or IV). The sarcomatous element was strongly positive for vimentin in all cases and focally positive for cytokeratin 7 in four cases, while the epithelial component showed a strong positivity for cytokeratin 7 and focal staining for vimentin, cytokeratin 20, CA-125 and CEA. CONCLUSION: Carcinosarcomas of the uterus and ovary are highly aggressive biphasic neoplasms with a prominent epithelial component. Their most common location is the uterine corpus. Although distant metastases are rarely found at the time of diagnosis, the prognosis of these tumors is unfavorable. The optimal chemotherapy remains to be determined.

Synchronous ovarian and endometrial carcinoma: a strong link to endometriosis?

PURPOSE: To further study the clinicopathological features of synchronous ovarian and endometrial carcinomas. METHODS: We retrospectively studied all cases of synchronous ovarian and endometrial carcinomas diagnosed in our laboratory over the last 15-year period. The pathological findings were correlated with the clinical records of the patients. RESULTS: Seven cases of synchronous primary ovarian and endometrial carcinomas were retrieved. The most common presenting symptom was abnormal vaginal bleeding (5 cases, 71.4%). Five patients (71.4%) were postmenopausal and two (28.6%) were nulliparous. All seven patients had Stage I ovarian and endometrial carcinomas of endometrioid histology. Moreover, in all seven ovarian carcinomas endometriosis foci were observed, while atypical endometriosis was found in four of them. With the exception of one patient, who received adjuvant postoperative radiation, all remaining patients were treated with surgery alone. All patients were alive and free of disease at completion of the study. CONCLUSION: The correct classification of synchronous primary ovarian and endometrial carcinomas is often problematic because of the frequent confusion with their metastatic counterparts. Although the exact etiology remains unclear, endometriosis seems to be a major risk factor for their development.

Vaginal cysts: a common pathologic entity revisited.

PURPOSE: To further study the clinicopathological features of benign vaginal cysts. METHODS: We retrospectively studied all cases of benign vaginal cysts diagnosed in our laboratory over the last decade. Pathological findings were correlated with the clinical records of the patients and histochemistry results. RESULTS: Forty cases of benign vaginal cysts were retrieved. There were 12 cases of mullerian cysts (30.0%), 11 cases of Bartholin's duct cysts (27.5%), ten cases of epidermal inclusion cysts (25.0%), five cases of Gartner's duct cysts (12.5%), one endometrioid cyst (2.5%) and one unclassified cyst (2.5%). Patient age ranged from 20 to 75 years with a mean of 35 years, and a peak incidence between 31-40 years (13 cases, 32.5%). The majority of patients were asymptomatic (31 cases, 77.5%). The cyst type which was more frequently associated with symptoms was Bartholin's duct cyst. Most lesions were located in the left-lateral vaginal wall (13 cases, 32.50%). Mullerian cysts were lined by columnar endocervical-like or cuboidal epithelium, whereas Gartner's duct cysts were all lined by cuboidal epithelium. Epidermal inclusion cysts were lined by stratified non-keratinizing squamous epithelium. Bartholin's duct cysts were lined by transitional, mucin-rich columnar or squamous epithelium and were frequently accompanied by inflammation. CONCLUSION: Benign vaginal cysts are in the majority of cases asymptomatic and are often incidentally discovered during gynecological examination for other purposes. The differential diagnosis between Mullerian and Gartner's duct cysts requires histochemical evaluation of epithelial mucin production. The pathogenesis of most types of vaginal cysts remains to be clarified.

Fetal ovarian cysts: report of two cases and literature review.

In the present study we report two cases of fetal ovarian cysts. In the first case the cyst was initially discovered during prenatal ultrasound examination, while in the second case the cyst was identified during autopsy examination of a stillborn fetus. Pathologic examination of both specimens revealed similar histology, which was mainly characterized by the presence of an ovarian cortex comprising several maturing and primordial follicles which were occasionally biovular, and a focal lining of luteinized theca cells. Another prominent feature was the presence of multiple deposits of dystrophic calcifications within the cyst wall. Both cysts were diagnosed as follicular in origin.

A malignant eccrine poroma in a pregnant woman: case report and review of the literature.

Malignant eccrine poroma is a rare cutaneous neoplasm that originates from the intraepidermal portion of the eccrine gland. It affects mainly elderly people while its occurrence in younger adults is extremely rare. We present the first reported case of a malignant eccrine poroma in a pregnant woman, with emphasis on its pathologic and immunohistochemical features. Early diagnosis and treatment of eccrine neoplasms are of crucial importance when pregnancy coexists, because of their tendency to aggravate under the influence of gestation-related changes.

The prognostic value of PTEN, p53, and beta-catenin in endometrial carcinoma: a prospective immunocytochemical study.

Mutations of the PTEN, p53, and beta-catenin genes are the most frequent molecular defects in endometrial carcinomas. The aim of this study was to investigate their prognostic significance in this form of cancer. Imprint smears were obtained from 80 fresh endometrial tumor specimens and studied immunocytochemically for the expression of PTEN, p53, and beta-catenin proteins. The staining pattern was correlated with several well-established prognostic parameters, including 5-year survival. Positive staining of p53 was significantly correlated with increased stage (P < 0.0001), lymph node metastases (P = 0.001), and a nonendometrioid histology (P = 0.001). On the contrary, positive beta-catenin expression was significantly associated with decreased stage (P = 0.002), decreased grade (P = 0.007), and a negative lymph node status (P = 0.023). PTEN positivity was correlated with decreased stage (P = 0.002) and negative lymph nodes (P = 0.008). All the three markers affected survival significantly in univariate analysis but only beta-catenin had an independent prognostic impact. An independent prognostic significance was also shown for PTEN in the stage I subgroup of patients. The results of our study indicate that loss of beta-catenin expression is a strong and independent predictor of an unfavorable outcome in patients with endometrial carcinoma. Loss of PTEN may also be associated with a worse prognosis in patients with early-stage disease.

Malignant paraganglioma of the urinary bladder in a 44-year-old female: clinicopathological and immunohistochemical study of a rare entity and literature review.

Paraganglioma of the urinary bladder is a rare pathologic entity with no definitive histological, immunohistochemical or molecular features to determine its malignant potency. Malignancy is essentially determined by the presence of deep local invasion, invasion of adjacent structures, and lymph node or distant metastases. So far, up to 180 cases of paraganglioma have been reported, with less than 30 being malignant. We present a case of malignant paraganglioma of the urinary bladder in a 44-year-old woman. The patient's symptoms were painless hematuria and micturitional headache. The tumor presented the characteristic "zellballen" pattern of growth and immunohistochemically was positive for all neuroendocrine markers. The patient underwent partial cystectomy and the following two postoperative years were uneventful. The literature on paraganglioma of the urinary bladder, analyzing the histological, immunohistochemical and molecular characteristics, is reviewed.

Primary gestational choriocarcinoma of the uterine cervix. Report of a case and review of the literature.

Gestational choriocarcinoma usually arises in the uterine cavity and is associated with coincident or antecedent pregnancy. Extrauterine choriocarcinomas are very rare entities, and most of these are located in the uterine cervix. In our case, a 43-year-old woman was admitted in our hospital because she had amenorrhea for 2 months and elevated serum beta-human chorionic gonadotropin levels. The patient was considered to have an ectopic pregnancy. Initially, she was treated with methotrexate, but since there was a continuous rise in human chorionic gonadotropin levels, the patient underwent a laparoscopy, along with dilatation and curettage (D&C) of the uterine cavity. Histopathologic findings, including immunohistochemical study, led to the diagnosis of choriocarcinoma of the cervix. Finally, the patient underwent a transabdominal hysterectomy and received single agent chemotherapy with methotrexate. Our case represents a primary choriocarcinoma of the cervix, which was initially misdiagnosed as an ectopic pregnancy. The difficulties in differential diagnosis are discussed. Immunohistochemical evaluation remains the mainstay of the diagnosis in most cases. Choriocarcinoma has a very good prognosis even in advanced stages, since it is a very chemosensitive tumor.

Ovarian mucinous cystadenoma with extended calcification in an 11-year-old girl: case report and review of the literature.

The majority of ovarian masses in childhood and adolescence are non-epithelial in origin, with a predominance of germ cell tumors, while epithelial neoplasms comprise a small proportion of the total (approximately 15-20%). Mucinous cystadenomas in particular are only sporadically reported in this age group. We present a case of an ovarian mucinous cystadenoma with extended calcification in a premenarchal 11-year-old girl. Pediatric mucinous cystadenomas of the ovary may on rare occasions display extended calcification. Careful evaluation of the remaining pathological features of the tumor is needed in order to avoid misinterpreting this relatively non-specific finding as a feature of malignancy.

Clinicopathological features of unusual vascular lesions of the pelvis, retroperitoneum and colon in females: a report of five cases and review of the literature.

Vascular lesions comprise benign and malignant neoplasms as well as non-neoplastic conditions that may be located in various sites but only rarely in the pelvis or the retroperitoneum. In our study we describe five diverse and unusual cases of vascular lesions of the pelvis, retroperitoneum and colon in female patients: a case of retroperitoneal angiosarcoma, pelvic hemangioendothelioma, pelvic angiomyxoma, retroperitoneal lymphangioleiomyomatosis and a case of diffuse cavernous hemangiomatosis of the colon, with emphasis on their clinicopathological features and differential diagnosis. The recent literature on the subject is also briefly reviewed.