Familiar and unfamiliar pseudoneoplastic lesions of the head and neck.

Pseudoneoplastic lesions in the head and neck are numerous. Familiarity with the sites of predilection and demographics of these lesions is particularly useful if the differential diagnosis for a minimal biopsy sample includes benign and malignant entities. This article is a brief overview of some common and unusual pseudo neoplasms specific to this region.

Oral mucoceles: a clinicopathologic review of 1,824 cases, including unusual variants.

PURPOSE: To review the clinicopathologic features of oral mucoceles, with special consideration given to unusual variants and exclusion of salivary duct cysts. MATERIALS AND METHODS: This was a retrospective consecutive case review of all oral mucoceles diagnosed by the Medical University of South Carolina, Oral Pathology Biopsy Laboratory, from 1997 to 2006. The following data were recorded: patient demographics, clinical features (anatomic location, color, size, and consistency), clinical impression, history of trauma, history of periodic rupture, and occurrence of unusual mucocele variants. RESULTS: During the study period, 1,824 oral mucoceles were diagnosed. Of these cases, 1,715 represented histopathologically confirmed cases that were not recurrences. There was no significant gender predilection, and the average age was 24.9 years. The most common locations were the lower labial mucosa (81.9%), floor of mouth (5.8%), ventral tongue (5.0%), and buccal mucosa (4.8%); infrequent sites included the palate (1.3%) and retromolar area (0.5%). The lesions most often were described as blue/purple/gray or normal in color. The mean maximum diameter was 0.8 cm (range, 0.1 to 4.0 cm). In 456 cases, a history of trauma was reported, and in 366 cases a history of periodic rupture was reported. Unusual variants included superficial mucoceles (n = 3), mucoceles with myxoglobulosis (n = 6), and mucoceles with papillary synovial metaplasialike change (n = 2). CONCLUSIONS: Our results confirm the findings of previous investigators regarding the major clinicopathologic features of oral mucoceles. Special variants of oral mucoceles occur infrequently, although it is important to recognize these variants to avoid misdiagnosis.

Microscopic Extranodal Extension in HPV-Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation.

OBJECTIVE: Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENEmi) and role of adjuvant concurrent chemoradiation (CRT) for ENEmi remain unclear. This study evaluates (1) the prognostic significance of ENEmi in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. STUDY DESIGN: Retrospective cohort study. SETTING: Commission on Cancer (CoC)-accredited facilities. METHODS: This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENEmi or no ENE who had undergone margin-negative surgery. The association of ENEmi with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENEmi receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. RESULTS: We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENEmi. On multivariable analysis, ENEmi was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENEmi who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). CONCLUSION: For patients with HPV-negative HNSCC, pN+ with ENEmi is associated with worse OS than pN+ without ENE. However, for patients with ENEmi, concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENEmi requires additional investigation.

Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear. Using a Simon's two-stage design, we present results of a single-arm phase-II trial where 12 patients with stage II-IVA OCSCC received 3 to 4 biweekly doses of 3 mg/kg nivolumab followed by definitive surgical resection with curative intent. Presurgical nivolumab therapy in this cohort shows an overall response rate of 33% (n = 4 patients; 95% CI: 12%-53%). With a median follow up of 2.23 years, 10 out of 12 treated patients remain alive. Neoadjuvant nivolumab is safe, well-tolerated, and is not associated with delays in definitive surgical treatment in this study. This work demonstrates feasibility and safety for incorporation of nivolumab in the neoadjuvant setting for OCSCC (ClinicalTrials.gov: NCT03021993).

Co-occurrence of Langerhans cell histiocytosis and Rosai-Dorfman disease: possible relationship of two histiocytic disorders in rare cases.

Rosai-Dorfman disease and Langerhans cell histiocytosis are both disorders of accessory immune cells. Two cases have been previously reported of concurrent Langerhans cell histiocytosis and Rosai-Dorfman disease. In this report, we characterize the findings and selected molecular studies in nine additional cases. Histology was reviewed. Immunohistochemical stains were performed on all cases in which slides or blocks were available. A combination of CD1a, S-100, CD3, CD20, langerin, CD68, CD163, CD21, CD35 and CD123 immunohistochemical stains were performed. High-resolution array comparative genomic hybridization was performed on six samples from five cases. In these cases, seven were female and two male, with an average age of 25 years (15 months-59 years). A majority of the cases were identified in lymph node. Areas of Langerhans cell histiocytosis had a typical appearance with the existence of bland 'coffee-bean' nuclei, clear cytoplasm and associated eosinophils. The immunophenotype was typical, including expression of CD1a, S100, CD68 and langerin. In areas of Rosai-Dorfman disease, there was emperipolesis seen in all cases. Cells were intermediate-large in size with large round nuclei and ample clear or pale cytoplasm. The lesional cells were positive for S100, CD68, CD163, without expression of langerin or CD1a. Array comparative genomic hybridization showed gains and/or losses in four of the six samples. One case showed no gains or losses and one additional case showed gains and losses in the Langerhans cell histiocytosis, while no abnormalities were discovered in the Rosai-Dorfman disease component. These findings are comparable to those seen in previous studies of Langerhans cell histiocytosis. We report the clinical and pathologic findings of the combination of Langerhans cell histiocytosis and Rosai-Dorfman disease. Furthermore, we suggest on the basis of evidence from our cases that, when simultaneous, the two entities may be pathophysiologically related.

Pseudomembranous disease (ligneous inflammation) of the female genital tract, peritoneum, gingiva, and paranasal sinuses associated with plasminogen deficiency.

Pseudomembranous disease (or ligneous inflammation) is a rare condition characterized by accumulations of fibrin-rich eosinophilic material. Recent investigations have linked the etiology of this condition to plasminogen deficiency (hypoplasminogenemia). Although much of the literature concerning this disease has focused upon the often clinically striking ocular manifestations, it is important to note that pathologic changes may develop in a variety of anatomic locations, including the oral cavity, upper and lower respiratory tract, female genital tract, kidneys, and gastrointestinal tract. Here, we report an unusual case of a 33-year-old woman who initially presented with gingival inflammation. In subsequent years, she developed additional signs and symptoms related to sinonasal and genital tract involvement. Despite numerous clinical evaluations, biopsies, and laboratory tests, the patient's diagnosis remained elusive for 7 years. Ultimately, it was the distinctive appearance of the gingiva that led to a diagnosis of plasminogen deficiency. Unfortunately, the complicated clinical course and elapsed time between initial presentation and diagnosis illustrated by the present case are not uncommon among patients with this condition. Greater familiarity with the clinical and histopathologic features of this condition among pathologists and treating clinicians is essential for timely diagnosis and management.

Data Set for the Reporting of Malignant Odontogenic Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

A data set has been developed for the reporting of excisional biopsies and resection specimens for malignant odontogenic tumors by members of an expert panel working on behalf of the International Collaboration on Cancer Reporting, an international organization established to unify and standardize reporting of cancers. Odontogenic tumors are rare, which limits evidence-based support for designing a scientifically sound data set for reporting them. Thus, the selection of reportable elements within the data set and considering them as either core or noncore is principally based on evidence from malignancies affecting other organ systems, limited case series, expert opinions, and/or anecdotal reports. Nevertheless, this data set serves as the initial step toward standardized reporting on malignant odontogenic tumors that should evolve over time as more evidence becomes available and functions as a prompt for further research to provide such evidence.

Data Set for the Reporting of Oral Cavity Carcinomas: Explanations and Recommendations of the Guidelines From the International Collaboration of Cancer Reporting.

The International Collaboration on Cancer Reporting is a nonprofit organization whose goal is to develop evidence-based, internationally agreed-upon standardized data sets for each cancer site for use throughout the world. Providing global standardization of pathology tumor classification, staging, and other reporting elements will lead to the objective of improved patient management and enhanced epidemiologic research. Carcinomas of the oral cavity continue to represent a significant oncologic management burden, especially as changes in alcohol and tobacco use on a global scale contribute to tumor development. Separation of oral cavity carcinomas from oropharyngeal tumors is also important, as management and outcome are quite different when human papillomavirus association is taken into consideration. Topics such as tumor thickness versus depth of invasion, pattern of invasive front, extent and size of perineural invasion, and margin assessment all contribute to accurate classification and staging of tumors. This review focuses on the data set developed for Carcinomas of the Oral Cavity Histopathology Reporting Guide, with discussion of the key elements developed for inclusion.

Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary.

Most primary ovarian mucinous tumors are of surface epithelial-stromal origin and exhibit diffuse expression of cytokeratin 7 (CK7) combined with variable expression of cytokeratin 20 (CK20); this immunoprofile distinguishes them from most lower gastrointestinal tract tumors secondarily involving the ovaries. The uncommon ovarian mucinous tumors of germ cell (teratomatous) origin have not been extensively evaluated to determine the utility of these markers and other markers of intestinal differentiation for distinguishing these tumors from metastatic gastrointestinal tract mucinous tumors. Immunohistochemical expression of CK7, CK20, CDX2, and villin was assessed in 44 ovarian mucinous tumors associated with a mature cystic teratoma. All cases lacked evidence of a nonovarian primary mucinous tumor. All mucinous tumors were unilateral; 6 cases had bilateral teratomas. All tumors displayed gastrointestinal-type mucinous differentiation, with epithelium that was commonly goblet cell-rich or hypermucinous; 21 were associated with pseudomyxoma ovarii and 3 of these had pseudomyxoma peritonei. Tumor architecture ranged from purely cystadenomatous (n=24), to proliferative (n=13), to carcinomatous (n=6); some tumors had admixtures of these patterns. One tumor had a goblet cell carcinoidlike pattern with pseudomyxoma ovarii. Three carcinomas had a signet ring cell component. Cystadenomatous tumors without pseudomyxoma ovarii (n=15) exhibited all possible CK7/CK20 coordinate expression profiles with nearly equal frequency. All proliferative tumors without pseudomyxoma ovarii (n=8) expressed CK7, most often in combination with CK20 expression. All cystadenomatous and proliferative tumors with pseudomyxoma ovarii (n=9 and n=5) were CK7-/CK20+. All carcinomatous tumors had pseudomyxoma ovarii; 3 were CK7-/CK20+, 2 were CK7+/CK20+, and 1 was CK7+/CK20-. The presence of pseudomyxoma ovarii was significantly associated with a CK7-/CK20+ profile (86% with pseudomyxoma ovarii vs. 13% without, P<0.0001), CDX2 positivity (79% vs. 0%, P<0.0001), and villin positivity (57% vs. 5%, P=0.0009). A subset of mucinous tumors associated with mature cystic teratomas exhibiting morphologic and immunohistochemical features of lower intestinal tract-type mucinous tumors may be teratomatous in origin. In practice, the more common diagnosis of secondary involvement by a lower intestinal tract mucinous tumor should be addressed in the pathology report and in subsequent clinical evaluation; interpretation as a true primary ovarian mucinous tumor of teratomatous origin can be considered as an alternative diagnosis when evaluation and follow-up fail to identify a nonovarian source of the mucinous tumor. Those tumors having CK7 expression with or without CK20 expression may be derived from upper gastrointestinal tract-type or sinonasal-type teratomatous elements but could be independent tumors of surface epithelial-stromal origin.

Efficacy of sumatriptan tablets in migraineurs self-described or physician-diagnosed as having sinus headache: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Many patients and physicians interpret episodic headache in the presence or absence of nasal symptoms as "sinus' headache, while ignoring the possible diagnosis of migraine. OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in patients with migraine presenting with "sinus" headache. METHODS: A randomized, double-blind, placebo-controlled, multicenter study was conducted in adult (aged 18-65 years) migraine patients presenting with self-described or physician-diagnosed "sinus" headache. From November 2001 to March 2002, patients meeting International Headache Society criteria for migraine (with > or =2 of the following: unilateral location, pulsating quality, moderate or severe intensity, aggravation by moderate physical activity; and > or =1 of: phonophobia and phonophobia, nausea and/or vomiting) and with no evidence of bacterial rhinosinusitis were enrolled and randomized in a 1:1 ratio via computer-generated randomization schedule to receive either 1 sumatriptan 50-mg tablet or matching placebo tablet. The primary efficacy end point was headache response (moderate or severe headache pain reduced to mild or no headache pain) at 2 hours after administration. The presence or absence of migraine-associated symptoms and sinus and nasal symptoms was also measured. Tolerability was assessed through patient-reported adverse events (AEs). RESULTS: Two hundred sixteen patients with self-described or physician-diagnosed "sinus" headache received a migraine diagnosis and treated 1 migraine attack with sumatriptan 50 mg. The efficacy (intent-to-treat) analysis included 215 patients treated with sumatriptan 50 mg (n = 108; mean [SD] age, 39.6 [12.3] years; mean [SD] weight, 77.7 [17.7] kg; sex, 71% female; race, 69% white) or placebo (n = 107; mean [SD] age, 41.0 [11.3] years; mean [SD] weight 80.7 [20.9] kg; sex, 69% female; race, 64% white). Significantly more patients treated with sumatriptan 50 mg achieved a positive headache response at 2 and 4 hours after administration compared with those treated with placebo (69% vs 43% at 2 hours and 76% vs 49% at 4 hours, respectively; both, P < 0.001). Significantly more sumatriptan-treated patients were free from sinus pain compared with placebo recipients at 2 hours (63% vs 49% placebo, P = 0.049) and 4 hours (77% vs 55%, P = 0.001). All treatments were generally well tolerated. The most common drug-related AEs reported in the sumatriptan and placebo groups, respectively, were dizziness (5% vs < 1%), nausea (3% vs 2%), other pressure/tightness (defined as sense of heaviness; heaviness of upper body, upper extremities; jaw tension; neck tension) (4% vs 0%), and temperature sensations (defined as warm feeling of back of neck, or flushing) (2% vs 0%). No patients experienced any serious AEs. CONCLUSIONS: Sumatriptan 50-mg tablets were effective and generally well tolerated in the treatment of these patients presenting with migraine headaches that were self-described or physician-diagnosed as sinus headaches.

Peritoneal Deciduoid Mesothelioma: An Unusual Presentation Complicating an Already Challenging Diagnosis.

This report highlights a diagnostically challenging case of diffuse deciduoid mesothelioma occurring in the peritoneum of a 25-year-old woman, 8 months postpartum. Optimally debulked tumor consisted of sheets of polygonal cells arranged in solid, trabecular, and pseudopapillary configurations, with vesicular, occasionally grooved nuclei and small nucleoli. A barrage of immunohistochemical stains revealed an unusual staining pattern characterized by diffusely positive keratin, WT-1, and mesothelin staining, but lack of calretinin positivity. Electron microscopy demonstrated only rare thin, long, branching cellular projections. Cytogenetics revealed balanced translocations of 12p and 1q and 16p. Based on compiled ancillary studies, a diagnosis of deciduoid mesolthelioma was made and supported by consultations from experts at 3 outside facilities. Twenty-seven months after diagnosis, the patient is alive and undergoing treatment with progression of disease. This case is presented in detail, and a discussion of the diagnostic criteria and current application of those criteria is provided.

Merkel cell carcinoma: does tumor size or depth of invasion correlate with recurrence, metastasis, or patient survival?

OBJECTIVE: The objective of this retrospective study and literature review was to compare the clinical and histologic criteria including tumor size and depth of invasion with outcomes in patients with Merkel cell carcinoma. METHODS: The state cancer registry provided patients (n = 46) diagnosed with Merkel cell carcinoma from 1992 through 2002. Pathology slides were reviewed by the author for tumor size, depth of invasion, Clark level, and margin status. Further clinical information and survival data were gathered from patient records. Statistical analysis was performed using t tests and Kaplan-Meier survival curves. Patients were excluded from specific analysis based on misdiagnosis, unavailability of pathology slides, absent medical records, or those lost to follow up. RESULTS: Disease-free survival rates were 52%, 39%, and 9% at 1, 2, and 5 years, respectively. The average disease-free interval was 18.4 months (range, 1-80 months). No correlation was found between tumor size (P = .49), depth (P = .41), or Clark level (P = .82) to overall survival. A trend was found comparing tumor size or depth of invasion with local recurrence (P = .07) but with no correlation to regional recurrence (P = .93 and P = .60) or distant metastasis (P = .16 and P = .24). Overall recurrence was found in 60.7% of patients with local recurrence occurring in 18.1%, regional recurrence 40.9%, and distant recurrence 47.8%. Comparing patients with positive versus negative margins at initial excision, local recurrence was found in 33.3% versus 9.09% (P = .19), regional recurrence 66.6% versus 27.2% (P = .08), and distant metastasis 66.6% versus 45.4% (P = .36), respectively. CONCLUSIONS: No correlation was found between tumor size or depth of invasion to patient survival or metastasis. However, there was a trend toward increased local and regional recurrence rates when comparing size and depth and in specimens with positive tumor margins. These outcomes are consistent with those reported in recent literature and further characterize the unpredictable nature of this disease. An aggressive approach should be taken, including wide local excision with negative tumor margins and lymph node dissection; however, larger multistate reviews are needed for additional support.

Prevalence of migraine in patients with a history of self-reported or physician-diagnosed "sinus" headache.

BACKGROUND: Symptoms referable to the sinus area are frequently reported during migraine attacks, but are not recognized in diagnostic criteria. Underrecognition of migraine may be partly attributed to a variable clinical presentation, and migraines with "sinus" symptoms contribute to this problem. This study was conducted to determine the prevalence of migraine-type headache (International Headache Society [IHS]-defined migraine without aura [IHS 1.1], migraine with aura [IHS 1.2], or migrainous disorder [IHS 1.7]) in patients with a history of self-described or physician-diagnosed "sinus" headache. METHODS: During a clinic visit, patients with a history of "sinus" headache, no previous diagnosis of migraine, and no evidence of infection were assigned an IHS headache diagnosis on the basis of headache histories and reported symptoms. RESULTS: A total of 2991 patients were screened. The majority (88%) of these patients with a history of self-described or physician-diagnosed "sinus" headache were diagnosed at the screening visit as fulfilling IHS migraine criteria (80% of patients) or migrainous criteria (8% of patients). The most common symptoms referable to the sinus area reported by patients at screening were sinus pressure (84%), sinus pain (82%), and nasal congestion (63%). CONCLUSIONS: In this study, 88% of patients with a history of "sinus" headache were determined to have migraine-type headache. In patients with recurrent headaches without fever or purulent discharge, the presence of sinus-area symptoms may be part of the migraine process. Migraine should be included in the differential diagnosis of these patients.

Pain-free results with sumatriptan taken at the first sign of migraine pain: 2 randomized, double-blind, placebo-controlled studies.

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan, 50-mg and 100-mg tablets, compared with placebo for treatment of migraine at the first sign of pain. PATIENTS AND METHODS: Two identical multicenter randomized, double-blind, placebo-controlled, single-attack studies were conducted from May through November 2000 in adults (aged 18-65 years). Patients treated migraine at the first sign of pain, while pain was mild, but not more than 2 hours after onset with oral sumatriptan, 50 mg or 100 mg, or matching placebo. The primary end point was pain-free relief at 2 hours after treatment with 50 mg of sumatriptan compared with placebo. RESULTS: There were 354 patients in study 1 and 337 patients in study 2. Significantly more patients treated with sumatriptan, 50 mg and 100 mg, were completely free from pain 2 and 4 hours after treatment vs patients treated with placebo (at 2 hours, 50% and 57% vs 29%; at 4 hours, 61% and 68% vs 30%; for both, P < .001). Also, significantly more patients treated with sumatriptan, 50 mg and 100 mg, were migraine-free (no pain or associated symptoms) vs those treated with placebo at 2 and 4 hours after treatment (at 2 hours, 43% and 49% vs 24%; at 4 hours, 54% and 63% vs 28%; for both, P < .001). The incidence of overall adverse events was low with the 50- and 100-mg dose of sumatriptan (placebo, 7%; sumatriptan at 50 mg, 14%; sumatriptan at 100 mg, 16%). CONCLUSIONS: Treatment of migraine at the first sign of pain with sumatriptan, 50-mg and 100-mg tablets, provides superior pain-free relief at 2 and 4 hours after treatment compared with placebo. Results of these studies suggest that sumatriptan at 100 mg may be more efficacious than at 50 mg when used in the early treatment paradigm. Because these studies were not powered to detect statistical differences between active doses, studies to investigate this finding are warranted.

Pain-free efficacy after treatment with sumatriptan in the mild pain phase of menstrually associated migraine.

OBJECTIVE: To estimate the efficacy of sumatriptan 50-mg and 100-mg tablets in menstrually associated migraine when treatment is administered during the mild pain phase. METHODS: A randomized, double-blind, placebo-controlled, single-attack study was conducted. Menstrually associated migraine was defined as any migraine beginning on or between day -2 and day 4, with day 1 = first day of flow. Patients had at least a 1-year history of migraine as defined by International Headache Society criteria and reported regularly occurring menstrually associated migraines typically having a mild pain phase. Patients treated attacks within 1 hour of the onset of pain but only if the pain was mild at onset and while the pain was still mild. RESULTS: In the 349 women with menstrually associated migraine, sumatriptan was significantly more effective than placebo: 61% and 51% of patients who used sumatriptan 100 mg and 50 mg, respectively, were pain-free 2 hours after treatment compared with 29% of patients who used placebo (P <.001 for both comparisons). At 2 hours, 51% and 45% of patients who used sumatriptan 100 mg and 50 mg were free of pain and associated symptoms (photophobia, phonophobia, nausea, vomiting) compared with 25% of placebo patients (P <.001 for both comparisons). Adverse events were low for sumatriptan 100 and 50 mg, and both doses were generally well tolerated. CONCLUSION: Sumatriptan 50-mg and 100-mg tablets are generally well tolerated and effective in providing pain-free relief and relief of the associated symptoms of menstrually associated migraine when administered in the mild pain phase.

The pharmacokinetics of sumatriptan when administered with norethindrone 1 mg/ethinyl estradiol 0.035 mg in healthy volunteers.

BACKGROUND: Because the majority of migraineurs are young women in their peak reproductive years, it is important to understand the possible effects on the pharmacokinetics of both medications when sumatriptan is coadministered with an oral contraceptive (OC). OBJECTIVES: The primary objective of this study was to assess the effect of multiple dosing of the OC norethindrone 1 mg/ethinyl estradiol 0.035 mg (NE/EE) on the single-dose pharmacokinetics of sumatriptan in healthy volunteers. Secondary objectives were to determine the effect of a single dose of sumatriptan on the multiple-dose pharmacokinetics of NE and EE, and to assess the safety and tolerability of the combination. METHODS: This was an open-label, 1-sequence, crossover study in healthy women who had been receiving NE/EE for at least 3 months. Subjects received 1 cycle of NE/EE, consisting of 21 days of OC and 7 days of placebo. They also received a single dose of sumatriptan 50 mg on the last day of the OC or placebo regimen. Blood samples for the determination of plasma sumatriptan concentrations were collected on days 21 and 28, and blood samples for the determination of plasma NE and EE concentrations were collected on days 20 and 21. Treatments were compared by analysis of variance. Equivalence between treatments was to be concluded if the 90% Cl for the ratio of reference to test means for log(e)-transformed parameters (area under the plasma concentration-time curve [AUCI and maximum measured plasma concentration [C(max)]) for each analyte fell within the interval 0.80 to 1.25. RESULTS: Twenty-six women (mean age, 29.8 years; age range, 18-44 years; weight range, 52-82 kg) participated in the study. The 90% CI for the ratio of reference to test means for the AUC extrapolated to infinity (AUC(infinity)) of sumatriptan was 1.11 to 1.22, and the 90% CIs for the AUC over the dosing interval at steady state (AUC(tau)) of NE and EE were 0.96 to 1.00 and 0.91 to 0.97, respectively. The 90% CIs for the ratio of reference to test means for the C(max) of sumatriptan, NE, and EE were a respective 1.05 to 1.30, 0.76 to 0.88, and 0.88 to 1.04. Study treatments were well tolerated. Adverse events were mild or moderate, and there were no clinically significant changes in vital signs or laboratory values. CONCLUSIONS: The extent of absorption (AUC) of sumatriptan, NE, and EE was similar after oral administration of sumatriptan and NE/EE, both alone and in combination. Thus, in the opinion of the study investigators, there were no clinically relevant changes in the AUC of any of the medications when sumatriptan and NE/EE were administered concomitantly compared with administration alone. The results of this study suggest that dose adjustment is not necessary when sumatriptan is administered concomitantly with NE/EE in healthy premenopausal women.

Interobserver and intraobserver variability in the histological dating of the endometrium in fertile and infertile women.

OBJECTIVE: To assess effects of biopsy timing and fertility status on inter- and intraobserver variability in dating of the endometrium. DESIGN: Endometrial biopsy slides randomly selected from a multicenter study testing the utility of biopsy in the diagnosis of infertility were distributed to three gynecologic pathologists, who estimated cycle day using standard criteria. Readers were blinded to the purpose of the study, patient age, fertility status, or timing of biopsy relative to LH surge or next menses. SETTING: Multicenter academic research programs in reproductive medicine. PATIENT(S): Eighty-two women with proven fertility, 83 infertile patients. INTERVENTION(S): Endometrial biopsy during midluteal (days 21-22) or late (days 26-27) luteal phase. MAIN OUTCOME MEASURE(S): Intraclass correlation coefficient (ICC), kappa. RESULT(S): Overall agreement was excellent (ICC 0.88); addition of readings by local pathologists decreased ICC only slightly. In subgroup analyses, ICCs were lowest for infertile women during the midluteal phase (0.65 vs. 0.71 for fertile women in the midluteal phase, and 0.88-0.90 for both groups in the late luteal phase). Intraobserver reliability was excellent (0.9-0.99). Agreement for diagnoses of "out-of-phase" was only moderate, with kappa values between 0.4 and 0.6. CONCLUSION(S): Observer variability in dating the endometrium was greatest in infertile women during the window of implantation.

Malignant odontogenic tumors: an update on selected tumors.

This is an update on selected odontogenic malignancies. The article deals with aspects of recognized odontogenic carcinomas, odontogenic sarcoma and a yet unrecognized entity, sclerosing odontogenic carcinoma. Odontogenic malignancies are exceedingly rare, complicating a thorough understanding of the biologic behavior, reproducible standardized diagnostic criteria, appropriate classification and clinical management. Without the knowledge of the tumor's biologic behavior, adequate clinical management is difficult and patient outcomes uncertain. The histopathologic features are emphasized as well as the more recent biomarker findings. These recent advances may facilitate further understanding of this group of malignancies and provide useful stratification to guide patient management.

Sclerosing rhabdomyosarcoma: report of a case arising in the head and neck of an adult and review of the literature.

Sclerosing rhabdomyosarcoma is a unique rhabdomyosarcoma variant, characterized by a prominent hyalinizing matrix. A notable pitfall is the potential for the unusual matrix and often pseudovascular growth pattern of this lesion to lead to confusion with other sarcoma types, including osteosarcoma, chondrosarcoma, and angiosarcoma. Here we report a case of sclerosing rhabdomyosarcoma arising in a 40-year old male. The tumor was centered in the pterygomaxillary fossa with extensive infiltration into adjacent structures. Fine needle aspiration yielded a preliminary diagnosis of high-grade pleomorphic undifferentiated sarcoma, for which he received neoadjuvant chemotherapy and surgical resection. Microscopic examination showed a malignant spindled to round cell neoplasm with prominent osteoid-like, hyaline stroma. Focal rhabdomyoblastic differentiation and diffuse immunoreactivity for desmin and myogenin aided in diagnosis. Nineteen months status post primary resection, the patient expired with multiple lung and bony metastases. Among 39 cases reported thus far (including the present case), there is a broad age range (0.3-79 years), with an average age at presentation of 27 years. The most commonly involved sites are the extremities (n = 19) and head and neck (n = 15). Most cases have been treated by resection, often combined with radiation and/or chemotherapy. Out of 31 cases with follow-up information provided, 6 patients developed local recurrence, 7 patients developed regional or distant metastasis, and 5 patients died of disease. Herein we discuss the ongoing controversy regarding how sclerosing rhabdomyosarcoma might best fit into existing rhabdomyosarcoma classification schemes, based upon current clinicopathologic and molecular genetic evidence.