Epithelioid hemangioma of the penis: a clinicopathologic and immunohistochemical analysis of 19 cases, with special reference to exuberant examples often confused with epithelioid hemangioendothelioma and epithelioid angiosarcoma

Epithelioid hemangiomas of the penis are very rare. To date, less than 10 examples have been reported in the English language literature. In this report, we describe the clinical, histopathologic, and immunohistochemical findings in 19 cases retrieved from our files. The patients ranged in age from 23 to 75 years (median age, 45 years) at the time of initial surgical resection. Seventeen patients presented with a solitary mass, and two presented with two separate, but closely approximated, lesions. The process involved the glans penis (n = 3), shaft (n = 11), base of the penis (n = 2), or penis, not otherwise specified (n = 3). The lesions ranged in size from <0.5 to 2.5 cm (median size, approximately 1.2 cm) in greatest dimension. Eleven examples were specifically noted to be dorsally located, and only one was stated to be ventral. Localized pain or tenderness was the most common complaint, documented in 12 cases. The preoperative duration of the lesions ranged from 5 days to 1 year (median 4.5 months). Microscopically, all examples contained a tumefactive proliferation of epithelioid endothelial cells, often in a nodular or lobular configuration and associated with an inflammatory infiltrate containing lymphocytes and eosinophils. In 14 cases, the vascular proliferation was associated with a small arterial segment, sometimes with mural damage and frequently (n = 13) with intraluminal epithelioid endothelial cells. Based on the growth pattern of the epithelioid endothelial cells, 13 cases were considered "typical," and six were considered exuberant or "atypical." The latter examples had a prominent centrally located zone where nests or sheet-like aggregates of epithelioid endothelial cells did not form discrete vessels. Immunohistochemical data are available for 15 tumors. The epithelioid endothelial cells usually had strong reactivity for CD31, lesser reactivity for factor VIIIrAg, and minimal reactivity for CD34. In 9 of 12 cases, a small number of epithelioid endothelial cells expressed keratins. In all cases tested, at least focal muscle-specific actin-positive myopericytic cells were present bordering the endothelial cells, and this was especially notable peripherally. Initial surgical intervention consisted of either a shave biopsy (n = 1), excisional biopsy (n = 2), or local excision (n = 16). A complete follow-up history is available for 12 patients, and incomplete follow-up information is available for an additional four patients. One patient developed a new epithelioid hemangioma at a site within the penis separate from the initial lesion, but no patient is known to have experienced a true metastasis or to have died of complications of this process. Optimal management appears to be complete local excision with periodic follow-up visits to monitor for local recurrence.     

Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine cases including one with dedifferentiation

Leiomyosarcomatous (LMS) differentiation is a rare event in liposarcoma (LPS) and may consist of either well-differentiated liposarcoma (WDL) with an intrinsic smooth muscle component, so-called "lipoleiomyosarcoma," (L-LMS) or dedifferentiated liposarcoma having smooth muscle differentiation in the dedifferentiated zones. The latter are high-grade sarcomas, whereas the behavior of the former group is uncertain. Specifically, it is not clear whether the presence of LMS negatively affects the prognosis. We present our experience with nine cases, the largest to date. The patients (seven male, two female) ranged in age from 42 to 65 years (mean 54 years). The tumors were usually large (2 to >40 cm [mean 17 cm]) tumors in the retroperitoneum (two cases), paratesticular-inguinal region (three cases), mediastinum (one case), lung (one case), abdomen (one case), and popliteal fossa (one case). The nine cases qualified as L-LMS and showed typical WDL with a multifocal, gradual transition into smooth muscle areas. The latter areas accounted for a variable portion of the lesions (range 5-90%) and were of low cellularity, mild to moderate nuclear atypia, and low mitotic activity. These areas seemed to arise from or blend with the smooth muscle in the walls of large vessels within the tumor. One case showed areas of dedifferentiation consisting of actin and desmin-negative, high-grade sarcoma. Follow-up in seven cases (range 26-312 months; mean 119 months) showed multiple local recurrences in seven patients and no metastases. Three patients are currently without evidence of disease (follow-up duration 26-312 months; mean 144 months) and four patients are alive with progressive disease (follow-up duration 60-132 months; mean 99 months). Our study suggests that L-LMS is a dual lineage sarcoma as evidenced by the fact that the smooth muscle component is often multifocal, not necessarily found in close association with the atypical changes in fat, and seemingly originates from atypical ("in situ") changes in the vessel wall. The LMS component, which is typically low grade, does not adversely affect the overall behavior of the tumor, which is similar to that of conventional WDL. LMS in L-LMS should not be misconstrued as evidence of low-grade dedifferentiation, a phenomenon that identifies a more unstable and potentially metastasizing lesion.     

Superficial low-grade fibromyxoid sarcoma (Evans tumor): a clinicopathologic analysis of 19 cases with a unique observation in the pediatric population

Low-grade fibromyxoid sarcoma (LGFMS), usually a deeply situated mass in adults, is uncommon in superficial soft tissue and in children. Nineteen superficial LGFMS from our files were studied for clinicopathologic features, the latter including tumor size, growth pattern, cellularity, collagen rosettes, vascularity, nuclear atypia, mitotic rate, necrosis, and immunophenotype. The patients included 12 males and 7 females who ranged in age from 2 to 70 years (mean, 29 years). There were 7 children. Tumor locations included the lower extremity (8), buttock (3), trunk (3), vulva/inguinal region (2), upper extremity (2), and unspecified subcutis (1). Clinical and histologic submitting diagnoses were mainly benign except for 3 cases, submitted as low-grade sarcoma, with only one as superficial LGFMS. The mean tumor size was 4.2 cm (range, 1.6-18 cm). Of 15 with evaluable resections, 5 had focal ink on tumor and 2 of these had known negative wider reexcisions. The tumors were relatively well circumscribed with low to moderate cellularity. The tumors alternated from myxoid zones with prominent curvilinear vasculature to collagenous fascicular zones. Collagen rosettes with peripheral round epithelioid cells and focal ischemic necrosis were present in 6 cases each. Mitotic rate was low (mean 1.6/50 HPF). Tumor cells were positive for vimentin and some were focally positive for actins, CD68, and EMA. CD34, keratins, and S-100 protein were negative. Follow-up (mean, 44 months; range, 10-84 months) on 16 patients demonstrated 14 with no evidence for disease, 2 with local recurrences at 5 and 16 months, but no metastases. Superficial LGFMS is more common than previously recognized and may affect children at a higher rate (7 of 19, 37%) than that for deep LGFMS. The prognosis is good and appears to be better than that for deep LGFMS.     

Lobular endocervical glandular hyperplasia, not otherwise specified: a clinicopathologic analysis of thirteen cases of a distinctive pseudoneoplastic lesion and comparison with fourteen cases of adenoma malignum.

We report 13 cases of a previously undescribed pseudoneoplastic lesion of the uterine cervix, which we have designated "lobular endocervical glandular hyperplasia, not otherwise specified." The patients' ages ranged from 37 to 71 years (mean, 45 years; median, 49 years). Three (27%) patients had a history of hormone use. Seven lesions were incidental findings in hysterectomy specimens. In the six other cases, the patient came to clinical attention because of a mucoid cervical discharge (two cases), increased vaginal discharge (two cases), abdominal discomfort (one case), or a 3.5-cm cervical mass found when being examined because of ovarian carcinoma (one case); hysterectomy was performed in each of these six cases. Microscopic examination showed a distinctly lobular proliferation of small to moderately sized rounded glands often centered around a larger central gland. The lobular proliferation was well to poorly demarcated and usually confined to the inner half of the cervical wall. Glands within the lobules were usually separated from each other by unaltered or hypercellular cervical stroma and were lined by columnar mucinous cells similar to the normal endocervix. Occasional reactive atypia of the endocervical cells and mitoses were seen, but no significant cytologic atypia was identified. Neither of the two cases stained showed cytoplasmic immunoreactivity for carcinoembryonic antigen. Follow-up of seven patients showed no evidence of recurrence of the cervical lesion, with an average length of follow-up of 3.4 years; three patients were lost to follow-up and three cases are recent. The principal consideration in the differential diagnosis was adenoma malignum (minimal deviation adenocarcinoma). The features most helpful in this distinction, in addition to the orderly lobular arrangement of the glands, were a lack of the following: irregular stromal infiltration, a desmoplastic stromal response, and focal malignant cytologic features. Lobular endocervical gland hyperplasia should be added to the list of previously described pseudoneoplastic glandular lesions of the cervix and, like them, not misinterpreted as neoplastic.     

Pigmented (melanotic) neurofibroma: a clinicopathologic and immunohistochemical analysis of 19 lesions from 17 patients

Neurofibromas with melanin-laden pigmented cells are rare, accounting for less than 1% of all neurofibromas accessioned to the Soft Tissue Registry of the Armed Forces Institute of Pathology between the years 1970 and 1996. This study analyzes the clinicopathologic features associated with 19 specimens removed from 17 patients. Eleven males and six females, ranging in age from 2 to 61 years (median, 28 years), participated in the study. Nine of 15 patients whose race was provided were black. Eight patients (47%) are known to have neurofibromatosis, and two others (12%) are strongly suspected of having this disorder; two patients have similarly affected family members. Eight patients were noted to have multiple skin tumors, and in each of two cases, two pigmented neurofibromas were available for review. Two patients had hypertrichosis and cutaneous hyperpigmentation resembling a hairy nevus, and one had a café au lait spot directly overlying a pigmented neurofibroma. Tumors ranged in size from 1.7 to 50 cm in greatest dimension and involved the buttock or leg (n = 6), head or neck (n = 8), trunk (n = 2), wrist or hand (n = 2), and an unspecified site (n = 1). The neurofibromas exhibited diffuse (n = 15), combined diffuse and plexiform (n = 2), combined diffuse and intraneural epithelioid (n = 1), and nonspecific (n = 1) growth patterns. The process involved the skin (n = 14), subcutis (n = 18), and/or skeletal muscle (n = 3). Wagner-Meissner-like bodies were identified in 11 tumors, and mitoses (average, less than one mitosis per 10 high-power fields) were present in three lesions. All examples contained scattered pigmented cells with dendritic, tadpole-shaped, spindled or epithelioid morphology. These cells were positive with Fontana-Masson (nine of nine) and Warthin-Starry (pH, 3.2; four of four) stains, and were depigmented with a melanin bleach method (two of two). An iron stain was negative. The tumors had immunoreactivity for S-100 protein (11 of 11), HMB-45 ( 10 of 11), Melan-A (four of four), tyrosinase (four of four), and CD34 (four of four). Although recurrences are documented, none of the tumors are known to have undergone malignant transformation. A pigmented neurofibroma can be confused with a pigmented dermatofibrosarcoma protuberans (Bednár tumor) because the melanin-laden cells of both processes are similar. However, the latter entity exhibits a more extensive storiform growth, has greater immunoreactivity for CD34, and lacks a diffuse proliferation of S-100 protein-positive Schwann cells.     

Spindle cell (sarcomatoid) carcinoma of the breast: a clinicopathologic and immunohistochemical analysis of 29 cases

Spindle cell (sarcomatoid) carcinoma of the breast is a rare variant of breast cancer that has been classified under the broad rubric of metaplastic carcinoma. Because the term "metaplastic carcinoma" comprises a heterogeneous group of tumors, it has been difficult to reliably predict biologic potential or to determine optimal therapy. To better characterize the spindle cell subset of metaplastic breast carcinomas, we reviewed 29 cases. All patients were adult females ranging from 40 to 96 years of age (median, 68 years). Tumor size ranged from 1.5 to 15 cm (median, 4 cm). Treatment was by excision and/or mastectomy with axillary node evaluation in most cases, often combined with postoperative radiation and/or chemotherapy. All cases were clinically of breast origin, showed >or=80% spindled/sarcomatoid morphology, and demonstrated keratin positivity and/or close association with ductal carcinoma in situ. Immunohistochemical studies showed evidence suggesting myoepithelial differentiation as exhibited by immunoreactivity for smooth muscle actin, cytokeratin 14, and p63 in a subset of cases (39%). Twenty-seven cases exhibited pure spindled or sarcomatoid morphology of variable appearance and nuclear grade, whereas 2 contained high-grade invasive ductal carcinoma comprising 相似文献   

Endometrial endometrioid adenocarcinoma with a deceptive pattern of spread to the uterine cervix: a manifestation of stage IIb endometrial carcinoma liable to be misinterpreted as an independent carcinoma or a benign lesion

The prognosis of endometrial endometrioid adenocarcinoma is determined in part by stage; endocervical stromal involvement (stage IIB) imparts a worsened prognosis. We describe a deceptive pattern of stage IIB disease that mimics a primary endocervical glandular proliferation and may lead to understaging of endometrial endometrioid adenocarcinoma. Fifteen cases of endometrial endometrioid adenocarcinoma with a peculiar pattern of cervical involvement were identified from our consultation files. All cases were referred in consultation because of doubt about the nature of the cervical process and its relation to the corpus tumor; in a few instances, the cervical proliferation was considered possibly benign and in one case was misinterpreted as mesonephric hyperplasia. The patients ranged from 49 to 84 years in age (mean age 64.9 years). There was usually a grossly evident endometrial tumor. The cervix was unremarkable grossly in at least 11 patients. The cervical tumors were composed of variably shaped, often tubular glands with little or no stromal response and mainly invaded as widely spaced glands that often appeared deceptively benign. In 14 cases luminal secretions, mainly eosinophilic, were identified, often leading to consideration of a mesonephric lesion. Ten of the endometrial tumors were grade 1, four grade 2, and one grade 3. One was noninvasive, nine superficially invasive, and five deeply invasive. In four cases myoinvasion had, at least in part, a diffusely infiltrative pattern. The tumors in the cervix showed no in situ component and no definite surface involvement. Continuity with the corpus tumor could be demonstrated in 12 cases. Ten of the cervical tumors invaded more deeply than the endometrial tumor, four invaded to a similar depth, and only one was more superficial than its endometrial counterpart. The cervical and corpus tumors had a similar immunoprofile in nine cases: all were vimentin positive, eight estrogen positive and one negative, four carcinoembryonic antigen negative, and five with focal apical or rare cytoplasmic staining. This immunoprofile in conjunction with routine morphologic similarity between the two tumors and the usual documented continuity between them indicate that the cervical process represents spread from the endometrial endometrioid adenocarcinoma. It is important for both therapeutic and prognostic reasons that the cervical abnormality is not misinterpreted as a benign or malignant primary endocervical glandular process.     

Noninvasive and invasive micropapillary (low-grade) serous carcinoma of the ovary: a clinicopathologic analysis of 135 cases

Reports describing the behavior of micropapillary serous carcinomas (MPSCs) of the ovary have focused on those that are noninvasive. There are only very limited data on the behavior of those that are invasive. To further characterize the behavior of MPSCs, invasive versus noninvasive primary tumors were distinguished based on the presence or absence of destructive infiltrative growth. To qualify for inclusion, invasive MPSCs, like the noninvasive tumors, were required to display a micropapillary architecture and low-grade nuclei. A total of 135 cases of MPSC were identified: 96 noninvasive and 39 invasive. On follow-up, survival for 10 patients with stage I noninvasive and invasive MPSCs was 100%, and survival for women with stage II and III noninvasive and invasive MPSCs with noninvasive implants was 80%. In contrast, the 5-year and 10-year survival for patients with stage II and III noninvasive MPSCs with invasive implants was 85% and 55%, respectively. The 5-year and 10-year survival for women with invasive MPSCs and invasive implants was 55% and 45%, respectively. The median time from diagnosis to death for women with noninvasive and invasive MPSCs with invasive implants was 60 months (range 33-240 months). The indolent behavior of these low-grade carcinomas distinguishes them from conventional serous carcinomas, which are high-grade aggressive neoplasms. Five of six patients with small (<5 mm) MPSCs in whom follow-up was available presented with high stage disease. Of these five women, three are alive and well and two are alive with disease (one with invasive and one with noninvasive implants). Nearly three fourths of noninvasive MPSCs were associated with atypical proliferative serous tumors, adenofibromas, or both, and 62% of invasive MPSCs were associated with noninvasive MPSCs, atypical proliferative serous tumors, and adenofibromas, alone or in combination. In addition to the frequent mixtures of these tumor components, transitions between them were common. These data in conjunction with recent molecular genetic studies strongly suggest that MPSCs (low-grade carcinomas) arise from atypical proliferative serous tumors unlike conventional serous carcinomas (high-grade carcinomas), which appear to develop de novo. The findings provide further support for the hypothesis that there are distinct pathways of carcinogenesis for low-grade and high-grade serous carcinoma of the ovary.     

History of methicillin-resistant Staphylococcus aureus (MRSA) surgical site infection may not be a contraindication to ventral hernia repair with synthetic mesh: a preliminary report

Purpose

A history of methicillin-resistant Staphylococcus aureus (MRSA) surgical site infection presents a significant surgical dilemma as to the risk of subsequent mesh infection, even if no active infection is present. We investigated the outcomes of ventral hernia repair with synthetic mesh in patients with prior MRSA surgical site infections (SSIs).

Methods

All patients with a clean wound but prior MRSA SSI undergoing open ventral hernia repair with mesh by a single surgeon over a 3-year period were reviewed for the development of any major (need for readmission, operative debridement, or mesh removal) or minor SSI. All patients received peri-operative intravenous vancomycin and prolonged suppressive oral trimethoprim/sulfamethoxazole or doxycycline.

Results

Ten patients (male = 7, female = 3) with clean wounds and a history of MRSA SSI underwent open ventral hernia repair with retrorectus synthetic mesh placement. Mean follow-up was 13.5 ± 3.3 months. Overall, two patients (20 %) developed SSIs (minor = 2, major = 0). Both SSIs were successfully managed with therapeutic oral antibiotics and local wound care without need for surgical debridement or mesh removal. There have been no hernia recurrences in any of the patients.

Conclusions

Preliminary results suggest that history of MRSA infection may not be a contraindication to the use of synthetic mesh for ventral hernia repair. Macroporous lightweight meshes, combined with use of prolonged suppressive antibiotics and sublay retromuscular mesh placement that provides complete tissue coverage, should be further investigated as an acceptable prosthetic choice when planning a complex ventral hernia repair in the setting of prior MRSA SSI.     

Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by a host of gastrointestinal (GI) lesions that can mimic other conditions. METHODS: We reviewed clinical documentation and samples from 132 separate GI biopsy or resection sites on 20 CVID patients obtained over a 26-year period, including biopsies from the colon (34), esophagus (19), small intestine (38), and stomach (35), a partial gastrectomy, small bowel resection, colectomy, 2 cholecystectomies, and 1 appendectomy. RESULTS: There were 13 males and 7 females. Nine patients were children (10 y and younger) and 11 were adults. Age at diagnosis ranged from 6 months to 62 years (median, 35.5 y), and age at biopsy ranged from 10 months to 67 years (median, 38 y). Esophageal samples often showed intraepithelial neutrophils, accompanied by candida. Half of patients' esophageal biopsies had prominent intraepithelial lymphocytosis, one of which also had prominent apoptosis. The stomachs of 67% of patients lacked plasma cells. Most showed lymphoid aggregates. An increase in apoptosis was detected in biopsies from a third. About 20% had a lymphocytic gastritis pattern. Intraepithelial neutrophils were found in a subset, accompanied by various infections [cytomegalovirus (CMV), Helicobacter pylori, and Cryptosporidium]. Granulomas were found in 1 patient. Gastric adenocarcinoma was identified in one patient. There was a paucity of small bowel plasma cells in the majority of patients (68%). The small bowel showed prominent lymphoid aggregates in about half (47%). An increase in apoptosis was detected in specimens from about 20%. Increased intraepithelial lymphocytes (IELs) were found in samples from over half of patients (63%), most of whom (83%) also had villous blunting, mimicking celiac disease. Intraepithelial neutrophils were found in a subset (32%) and correlated with CMV and Cryptosporidium infections. Granulomas were seen in biopsies from 2 patients (11%). One patient had a collagenous enteritis pattern (accompanied by a collagenous colitis pattern). One patient had autoimmune enteritis; biopsies from this patient were initially relatively normal but later displayed prominent crypt apoptosis and loss of goblet cells. In colon samples, a paucity of plasma cells was seen in 10 patients (63%). The colon showed lymphoid aggregates in most patients (81%). Apoptosis was prominent in samples from half of the patients (50%). Biopsies from 6 patients had a lymphocytic colitis pattern (38%) and 2 patients had a collagenous colitis pattern. Intraepithelial neutrophils were found in samples from most patients (88%). Crypt distortion was seen in 6 of these patients (43%), thereby mimicking ulcerative or Crohn colitis. Granulomas were found in 3 patients (19%). CMV was detected in 1 patient. The appendix from 1 patient showed Cryptosporidium and acute serositis with a paucity of plasma cells and an increase in apoptosis. The gallbladder from 1 patient showed acute cholecystitis, and another patient's gallbladder lacked plasma cells. CONCLUSIONS: GI tract CVID displays a wide spectrum of histologic patterns. Its features can mimic lymphocytic colitis, collagenous enterocolitis, celiac disease, lymphocytic gastritis, granulomatous disease, acute graft-versus-host disease, and inflammatory bowel disease. In fact, in our series, we found patients with a prior diagnosis of celiac disease (25%) and inflammatory bowel disease (35%), including Crohn disease (15%). The diagnosis of CVID may be suspected on the basis of the lack of plasma cells in a GI biopsy, but because this feature is only present in about two-thirds of patients, the diagnosis cannot always be suggested in isolation of other clinical and laboratory findings.     

Renal Ewing’s sarcoma/primitive neuroectodermal tumor (PNET): a case series of 7 patients and literature review

BackgroundPrimitive neuroectodermal tumor (PNET) is a rare kind of sarcoma that is primarily found in the kidney and has a very poor prognosis. Here, we review and summarize the clinical data of patients with renal PNET in our center and follow up the patients for survival status. Although the current literature suggests that chemotherapy may benefit the survival of these patients, the information from our center suggests that this may not be the case.MethodsWe retrospectively analyzed the clinical data of patients with renal PNET diagnosed pathologically at Peking University First Hospital from January 1, 2007, to January 1, 2018. All of the patients were followed up for survival status.ResultsSeven patients with renal PNET were found. The ratio of males to females was 6:1. The median age was 29 years (21–72 years) at the time of diagnosis. The preoperative imaging examination showed a large renal mass protruding outwards from the renal contour, with internal necrosis and hemorrhage. Six/7 patients were diagnosed with distant metastasis or retroperitoneal lymph node metastasis. The main clinical manifestations of patients were pain (5/7) and fever (3/7). In immunohistochemistry, all patients’ samples were CD99 positive. All patients died in our follow-up, with an average overall survival (OS) of 12.09 months (1.90–26.77 months).ConclusionsAs a rare renal tumor, renal PNET has a propensity to occur in young males. Most patients have distant metastasis when they are diagnosed, and the prognosis is very poor. Effective treatments are urgently needed.     

Mucinous tumors of the ovary: a clinicopathologic analysis of 75 borderline tumors (of intestinal type) and carcinomas.

With the exception of benign cystadenomas, mucinous ovarian tumors are rare and heterogeneous neoplasms. They have been classified as either borderline tumors or carcinomas for almost 30 years. Subsequently, the borderline tumors have been subclassified into endocervical-like and intestinal types. The diagnostic criteria for distinguishing borderline tumors of the intestinal type from mucinous carcinomas have varied, making difficult the interpretation of prognostic information. More recently, a further subdivision of the former tumors into forms with only epithelial atypia and variants with focal intraepithelial carcinoma has been proposed. Consequently, in this study of 41 mucinous borderline tumors of intestinal type and 34 mucinous carcinomas, the former were also subdivided into 30 cases with mild to moderate atypia only and 11 with areas of intraepithelial carcinoma. All 30 purely borderline tumors were stage I tumors, and all 15 with follow-up information (including one case with microinvasion) were clinically benign. All 11 mucinous borderline tumors that had foci of intraepithelial carcinoma were also stage I neoplasms, and none of the eight patients with follow-up data (including one with microinvasive carcinoma) recurred. Thirty-four invasive carcinomas were subclassified into 15 expansile and 19 infiltrative subtypes. All 15 carcinomas with only expansile invasion were stage I; none of the 11 with follow-up data recurred. Three of nine patients with stage I infiltrative carcinomas with follow-up information had a fatal recurrence. Eight of the remaining 10 infiltrative carcinomas had extended beyond the ovary at the time of diagnosis (stages II and III); of the six patients with follow-up data, four died of tumor and two were alive with disease. In stage I carcinomas nuclear grade and tumor rupture correlated with unfavorable prognosis, but less than infiltrative invasion. However, all three fatal tumors were infiltrative carcinomas that had ruptured, and two contained grade 3 malignant nuclei. Combination of infiltrative invasion, high nuclear grade, and tumor rupture is a strong predictor of recurrence for stage I mucinous ovarian tumors. Among the 19 infiltrative tumors, 13 contained foci of anaplastic carcinoma. Of the seven patients with stage I tumors and follow-up data, only one patient whose tumor had ruptured intraoperatively had a fatal recurrence. The presence of anaplastic components in stage Ia (intact) carcinomas did not have an adverse effect in their outcome, even when the undifferentiated carcinomatous elements appeared in the form of mural nodules.     

Vulvar intraepithelial neoplasia of the simplex (differentiated) type: a clinicopathologic study including analysis of HPV and p53 expression

The simplex (differentiated) variant of vulvar intraepithelial neoplasia (VIN) has not been well characterized. The authors studied the clinicopathologic features of 12 cases of simplex VIN and obtained follow-up data to assess its relationship to vulvar invasive squamous cell carcinoma (InvSCC). Expression of p53 protein was analyzed immunohistochemically and compared with adjacent non-neoplastic epidermal lesions. Assessment of human papilloma virus (HPV) deoxyribonucleic acid was done by polymerase chain reaction amplification and in situ hybridization. All patients were of postmenopausal age (mean age, 66.8 years). Three patients had a history of prior vulvar InvSCC and one had a separate synchronous vulvar InvSCC. Squamous hyperplasia was present in the adjacent epidermis in 10 patients and lichen sclerosus (LS) was present in four patients. Histologically, simplex VIN differed from "classic" VIN by its highly differentiated features. The characteristic features included parakeratosis, thickened epidermis with elongated and anastomosing rete ridges, enlarged abnormal keratinocytes with premature eosinophilic cytoplasmic differentiation extending deeply within the epidermis, whorling of enlarged keratinocytes or keratin pearl formation within rete ridges, prominent intercellular bridges, and dysplastic basilar cells. One patient had minimal microinvasion (0.6 mm). Ten of 12 patients had positive p53 immunostaining staining with suprabasilar extension of p53 positive cells in each patient. The labeling index (LI) of basilar cells ranged from 0% to 99% (median, 94.5%). Non-neoplastic lesions in the adjacent epidermis had p53-positive basal cells in nine of 11 evaluable cases. The LI was significantly lower in these lesions, with a median of 4% in squamous hyperplasia and 7.5% in LS; none had suprabasilar extension of p53-positive cells. HPV (type 31/35/51) was identified in only one simplex VIN--a p53-negative lesion. Staining for p53 often delineated sharply the junction between simplex VIN and squamous hyperplasia. Four patients subsequently developed vulvar InvSCC at 5, 6, 9, and 55 months. All four InvSCCs were of the conventional keratinizing type and were HPV negative, as were the one synchronous and two prior InvSCCs. The authors conclude that (1) simplex VIN has a strong association with vulvar InvSCC and is a probable precursor lesion of HPV-negative vulvar InvSCCs, (2) HPV is very uncommon in simplex VIN and probably does not play an important role in its genesis, (3) alteration of the p53 gene appears to be involved in the development of simplex VIN, and (4) immunostaining for p53 protein may be helpful in the differential diagnosis of simplex VIN.     

Nitrous oxide exposure does not seem to be associated with increased mortality, stroke, and myocardial infarction: a non-randomized subgroup analysis of the General Anaesthesia compared with Local Anaesthesia for carotid surgery (GALA) trial

BACKGROUND: /st> Nitrous oxide has been associated with increased vascular risk in the perioperative period. Here, we conducted a secondary analysis of the GALA trial to ascertain the impact of nitrous oxide on outcomes after carotid surgery under general anaesthesia (GA). METHODS: /st> One thousand seven hundred and seventy-three patients underwent GA, but 158 patients were excluded from this analysis as nitrous oxide use was unknown. The decision to use nitrous oxide was at the discretion of the anaesthetist and was not randomized. Six hundred and seventy-one patients received nitrous oxide and 944 patients did not. Logistic regression was used to analyse the same primary outcome as the original trial (risk of death, stroke, or myocardial infarction within 30 days of the operation). RESULTS: /st> Patients who received nitrous oxide were more likely to have had coronary artery disease, peripheral vascular disease, and atrial fibrillation (all P<0.05). Overall, there were 35 (5.2%) primary outcome events in patients receiving nitrous oxide compared with 44 (4.7%) in those who did not [relative risk 1.12, 95% confidence interval (CI: 0.73, 1.73); P=0.63]. The adjustment for the imbalanced baseline variables using logistic regression reduced the point estimate of harm for nitrous oxide [adjusted odds ratio 1.09, 95% CI (0.68, 1.74); P=0.73]. CONCLUSIONS: /st> Given the greater prevalence of vascular risk factors in the nitrous oxide group and the lack of any definite effect on the primary outcome measure, these data do not support a clinically meaningful adverse effect of nitrous oxide on our composite outcome in patients undergoing carotid surgery.     

Benign calcaneal bone cyst and pathologic fracture--surgical treatment with injectable calcium-phosphate bone cement (Norian): a case report

Solitary calcaneal bone cysts are uncommon. Usually they measure 1/3 to 1/2 of the calcaneal length. Symptomatic calcaneal bone cysts are generally treated with open debridement and autologous bone grafting. We report a case of a patient with a displaced intra-articular calcaneal fracture who presents with a large benign calcaneal bone cyst. This patient was treated with debridement and filling of defect with injectable calcium-phosphate bone cement (Norian) and open reduction and internal fixation of the calcaneal fracture.     

Tenosynovial (extraarticular) chondromatosis: an analysis of 37 cases of an underrecognized clinicopathologic entity with a strong predilection for the hands and feet and a high local recurrence rate

Tenosynovial chondromatosis is a multinodular cartilaginous proliferation that arises from the tenosynovial membranes. This report describes the clinical, radiologic, and histopathologic findings in 37 cases of this uncommon entity. There were 17 males and 20 females, ranging in age from 20 to 86 years (mean and median age, 46 years). The process involved tenosynovium of the fingers (n = 19), feet (n = 8), wrists (n = 4), ankles (n = 2), hand, not otherwise specified, or palm (n = 2), knee (n = 1), and forearm (n = 1). Signs of disease or symptoms were present for 5 weeks to 18 years (median duration, approximately 2 years) before surgical excision. The two most common complaints were a painless mass and a mass that was mildly tender with pressure. None of the tumors had clinical, radiologic, or histopathologic evidence of articular or bone involvement. Histologically, all tumors consisted of a multinodular cartilaginous proliferation involving tenosynovium and/or subsynovial connective tissue. Mild or moderate atypia, as encountered in chondroma of soft parts and synovial chondromatosis, was a frequent finding. Follow-up information was available for 16 patients (43%). Only two patients with follow-up information remained disease free after their initial surgical procedure. Seven patients had one recurrence and seven patients had two or more recurrences. Tenosynovial chondromatosis appears to be an extraarticular counterpart of synovial (intraarticular) chondromatosis. Our review indicates this process is often confused with chondroma of soft parts, in part, because both entities have a predilection for the hands and feet. Diagnosis of this underrecognized entity is of clinical importance because of the high local recurrence rate.