Optic neuropathy from metastatic squamous cell carcinoma of the cervix: an unusual CNS presentation

BACKGROUND: Central nervous system (CNS) metastases from cervical carcinoma are uncommon events. Leptomeningeal involvement from cervical squamous cell carcinoma has not been extensively described. CASE: A 43-year-old woman with initial diagnosis of stage IB squamous cervical carcinoma at age 30 was treated with hysterectomy and left salpingo-oophorectomy. She recurred with nodal disease at age 39 and went into a clinical complete remission after chemotherapy and radiation treatment. Three years later, she presented with symptoms of optic neuropathy. Cerebral spinal fluid (CSF) was positive for squamous cells consistent with primary cervical squamous cell carcinoma. No measurable disease was evident outside of the CNS. CONCLUSION: Meningeal carcinomatosis from cervical squamous cell carcinoma involving optic nerves has not been reported. Rapid progression of this patient's CNS metastatic disease suggests this form of metastases may be more aggressive and carry extremely poor prognosis.     

Central zone histology of the prostate: a mimicker of high-grade prostatic intraepithelial neoplasia

The central zone (CZ) is located at the base of the prostate adjacent to the seminal vesicles. Its histology as a potential mimicker of high-grade prostatic intraepithelial neoplasia (PIN) has not been formally studied. Three groups were evaluated. Group 1 comprised 30 consecutive radical prostatectomy specimens assessed for the extent of CZ and of Roman arch and/or cribriform formation in the CZ. Group 2 comprised 100 consecutive cases of nonconsult prostate needle biopsies, screened in a random blinded fashion to identify CZ histology and the specificity of its identification on biopsy. Group 3 comprised 34 consult cases (1984 to the present) with CZ histology on needle biopsy. For group 1, the average maximum diameter of CZ histology was 5 mm. Two cases (6.7%) did not contain the classic features of CZ histology. The average amount of cribriform and/or Roman arch formation in the areas with CZ histology was 16.5%. In group 2, 10% of prostate needle biopsy cases had CZ histology. Of these, 80% were located on biopsy specimens designated as the base of the prostate, 10% were located in the base and midportion of the prostate, and 10% were located in the midportion of the prostate. For group 3, CZ histology occupied on average 32% of the involved core. The 2 most common histologic features were eosinophilic cytoplasm (97%) and location at the end of a core (97%). Other features were Roman arch formation (59%), a prominent basal cell layer (32%), cribriform formation (26%), and associated thick muscle bundles typical of bladder neck (24%). On average, cribriform and/or Roman arch formation occupied 22% of the CZ area seen on biopsy. Twenty-six of the consult cases were sent in with preliminary outside diagnoses. Of these, 21 (81%) were either PIN or atypical: 11 (42%) high-grade PIN, 7 (27%) PIN, and 3 (12%) atypical glands. Our findings show that CZ histology is distinctive, as seen in radical prostatectomy specimens. Less frequently it is found on needle biopsy, where the presence of Roman arch and/or cribriform formation mimics PIN. Recognition of the distinctive features of CZ histology (i.e., tall columnar cells with eosinophilic cytoplasm, prominent basal cell layer, and lack of cytologic atypia) can help avoid a misdiagnosis of PIN or "atypia" on needle biopsy.     

Prevalence of vulvar lichen sclerosus in a general gynecology practice

OBJECTIVE: To describe the rate of vulvar lichen sclerosus in 1 general gynecology practice. STUDY DESIGN: A database of 1,675 consecutive patients presenting in a 3-year period to a general gynecology practice was utilized to identify women with lichen sclerosus. Data included age, menopausal status, symptoms and physical examination findings. Pathology specimens were reexamined by a gynecologic pathologist to confirm the diagnosis of lichen sclerosus. RESULTS: Of the 1,675 patients, 28 (1.7%) had biopsy-proven vulvar lichen sclerosus. Nine patients been diagnosed previously, and 19 were new cases. The mean age at diagnosis was 52.6 years (SD +/- 15.9) versus 37.1 years (SD +/- 16.4) for those without lichen sclerosus (p < 0.001). Fifteen of the 28 patients (54%) were post-menopausal at the time of diagnosis. Of the 19 women with newly diagnosed lichen sclerosus, 8 (42%) were symptomatic. Of the 11 asymptomatic women, 7 (64%) had scarring of the clitoral prepuce or resorption of the labia minora. CONCLUSION: The rate of vulvar lichen sclerosus in 1 general gynecology private practice is approximately 1.7%. Clinicians must maintain a high index of suspicion to make the diagnosis, as at least one third of patients may be asymptomatic.     

The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN)

It has been proposed that low-grade vulvar and vaginal lesions (VIN 1 and VaIN 1) are flat condylomas and should be designated as such. Moreover, their relationship to high-grade lesions (VIN 3 and VaIN 3) is unclear. Accordingly, this study was undertaken to address these issues by comparing the distribution of human papillomavirus (HPV) types in vulvar and vaginal intraepithelial lesions. We identified 33 cases of VIN 1, 34 cases of VIN 3, 17 cases of VaIN 1, and 16 cases of VaIN 3. In addition, 36 cases of low-grade squamous intraepithelial lesion (LSIL) in the cervix and 116 cases of cervical high-grade squamous intraepithelial lesion were used for comparison. Polymerase chain reaction analysis was performed using both the Roche PGMY and DDL SPF 10 systems. In cases where HPV was detected, the majority of low-grade and high-grade lesions contained a single HPV type. However, a minority of cases were found to have multiple HPV types. Of the VIN 1 cases, a low-risk virus was seen in 22 (67%), with HPV 6 or 11 accounting for 14 (42%). A high-risk virus was detected in 14 (42%) of cases of which 2 (6%) contained HPV 16. Of the VIN 3 cases, all had high-risk HPV of which 31 (91%) were found to have HPV 16. Of the VaIN 1 cases, 6 (35%) were found to have low-risk HPV types. HPV 6 or 11 were not found in these cases. High-risk virus was seen in 13 (76%) VaIN 1 cases, with 1 (6%) containing HPV 16. HPV was detected in 15 of 16 (94%) VaIN 3 lesions, all of which had high-risk types. HPV 16 was found in 8 (50%). In contrast, 2 (6%) of cervical LSIL had low-risk HPV (HPV 6 and 11), whereas 34 (94%) of LSIL cases had high-risk HPVs. Of the cervical high-grade squamous intraepithelial lesion cases, 100% had high-risk HPVs of which 87 (75%) were found to have HPV 16. The findings demonstrate that a significant number of low-grade vulvar and vaginal lesions contain high-risk HPV types, supporting their designation as low-grade intraepithelial lesions rather than flat condylomas. The low frequency of HPV 16 in VIN 1 compared with VIN 3 suggests they are distinct lesions or that HPV 16 is critical in the progression to VIN 3. Finally, comparison of the distribution of HPV in the vagina and vulva suggests that VaIN is more closely related to cervical intraepithelial neoplasia than to VIN.     

Olfactory epithelial organotypic slice cultures: A useful tool for investigating olfactory neural development

Anin vitro slice culture was established for investigating olfactory neural development. The olfactory epithelium was dissected from embryonic day 13 rats; 400μm slices were cultured for 5 days in serum-free medium on Millicell-CM membranes coated with different substrates. The slices were grown in the absence of their appropriate target, the olfactory bulb, or CNS derived glia. The cultures mimic many features ofin vivo development. Cells in the olfactory epithelium slices differentiate into neurons that express olfactory marker protein (OMP). OMP-positive cells have the characteristic morphology of olfactory receptor neurons: a short dendrite and a single thin axon. The slices support robust axon outgrowth. In single-label experiments, many axons expressed neural specific tubulin, growth-associated protein 43 and OMP. Axons appeared to grow equally well on membranes coated with type I rat tail collagen, laminin or fibronectin. The cultures exhibit organotypic polarity with an apical side rich in olfactory neurons and a basal side supporting axon outgrowth. Numerous cells migrate out of the slices, of which a small minority was identified as neurons based on the expression of neural specific tubulin and HuD, a nuclear antigen, expressed exclusively in differentiated neurons. Most of the migrating cells, however, were positive for glial fibrilary acidic protein and S-100, indicating that they are differentiated glia. A subpopulation of these glial cells also expressed low-affinity nerve growth factor receptors, indicating that they are olfactory Schwann cells. Both migrating neurons and glia were frequently associated with axons growing out of the slice. In some cases, axons extended in advance of migrating cells. This suggests that olfactory receptor neurons in organotypic cultures require neither a pre-established glial/neuronal cellular terrain nor any target tissue for successful axon outgrowth. Organotypic olfactory epithelial slice cultures may be useful for investigating cellular and molecular mechanisms that regulate early olfactory development and function.     

Contrast nephropathy in lower limb angiography

AIM: This study examines the occurrence of contrast nephropathy in a series of 302 consecutive lower limb angiogram and angioplasty procedures. METHODS: Serum creatinine measurements, 1 and 3 days after the procedures, were used to identify cases of contrast nephropathy, defined as a 25% increase above initial creatinine. These cases were reviewed retrospectively. A total of 267 patients had 224 diagnostic, and 78 interventional lower limb angiographic procedures. Of these, 46% had pre-existing renal impairment (creatinine >118 micro mol/l), of whom 11% were on dialysis - dialysis patients were excluded from analysis of changes in creatinine. Repeat creatinine measurements were taken after 191 procedures. RESULTS: Contrast nephropathy occurred after 15 procedures: of whom 9 died, and 6 recovered. Of these patients, 11 were taking potentially nephrotoxic drugs and 9 had renal impairment. Precautions to avoid contrast nephropathy were taken in only 2 cases. Of the 9 deaths, 6 were associated with severe underlying disease processes, but 3 occurred directly as a result of contrast nephropathy. Contrast nephropathy has an incidence of 8% in this series: the incidence in acute limb-threatening ischaemia is double that for other cases. Death from renal failure is relatively rare, with an incidence of 1%. In uncomplicated angiography or angioplasty, where admission is not prolonged by a need for further treatment, the condition has no mortality. CONCLUSIONS: Accepted precautionary measures should be observed, and alternatives to conventional angiography should be considered - particularly where there is pre-existing renal impairment and other co-morbidity.     

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: diagnostic performance, human papillomavirus testing, and follow-up results

BACKGROUND: Current guidelines recommend colposcopy rather than high-risk human papillomavirus (HPV) testing for the evaluation of abnormal cervical cytology interpreted as "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" (ASC-H) based on data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion (ASCUS/LSIL) Triage Study (ALTS), which indicated that ASC-H had a significantly greater frequency of high-risk HPV positivity and underlying high-grade squamous intraepithelial lesions (HSIL) compared with ASCUS. The cytologic interpretations in the ALTS were expert consensus diagnoses rather than routine, single-pathologist readings. METHODS: The authors conducted a comparative analysis of Hybrid Capture 2 high-risk HPV positivity and frequency of histologically diagnosed HSIL for ASC-H and ASCUS to evaluate the performance of ASC-H as a cytologic interpretation subcategory and the potential utility of HPV testing for colposcopy triage of ASC-H in routine practice. RESULTS: Sixty-four of 96 patients with ASC-H (66.7%) were HPV-positive compared with 484 of 1079 patients with ASCUS (44.9%). Among the patients who had histologic follow-up, HSIL was identified in 18 of 45 patients (40.0%) with HPV-positive ASC-H compared with 27 of 266 patients (10.2%) with HPV-positive ASCUS (P < 0.0001) and 1 of 22 patients (4.5%) with HPV-negative ASC-H (P = 0.003); the latter result was similar to the finding of HSIL in 5 of 85 patients (5.9%) with HPV-negative ASCUS. The frequency of HPV-positive ASC-H in the current study (67%) was lower than that obtained in the ALTS for ASC-H (86%) but higher than that for ASCUS in both this study (45%) and in the ALTS (51% for all ASC; 63% for ASCUS, equivocal for LSIL). Underlying HSIL was detected in a similar percentage of patients with HPV-positive ASC-H in this study and in the ALTS (41%). CONCLUSIONS: The greater frequency of HPV positivity and the significantly increased risk of underlying HSIL for ASC-H compared with ASCUS indicated that ASC-H category utilization and performance are appropriate in this routine clinical practice setting. The lower frequency of HPV positivity for ASC-H compared with the ALTS data and the similar low risk of HSIL in HPV-negative ASC-H and HPV-negative ASCUS indicate that HPV testing for triage of ASC-H in routine practice has the potential to reduce the number of women who are referred for colposcopy without an increased risk of failure to detect HSIL among HPV-negative women, similar to its triage role for ASCUS.     

Measuring the rate of change of haemodynamic response at the onset of exercise in normal limbs and those with intermittent claudication

Patients with claudication have an inadequate haemodynamic response to exercise. Blood flow response will not only have a magnitude, but also a rate of change. There is scope for investigating these parameters, as manipulation of the factors which control them may benefit work to improve the treatment for claudication. This work compares the responses for patients with one normal limb and one with intermittent claudication. A custom-built ergometer allows unilateral, infragenicular plantar flexion exercise, whilst common femoral artery blood flow can be measured continuously by Duplex ultrasound. This apparatus was used to measure blood flow before, at the onset of and during a 5 W square-wave exercise stimulus in 15 patients. The claudicant group had a mean steady-state gain that was approximately half that of the normal group at around 170 ml min(-1) (p < 0.001) and a response time that was much shorter (p = 0.006). A mean response time of 21.0 +/- 1.4 s was achieved in claudicant limbs compared to 31.8 +/- 2.9 s in normals. However, the average rate of change of blood flow during this response time was estimated to still be greater for the normal group, at 431.7 +/- 47.1 ml min(-2), than for the claudicant group. The differences in magnitude and rate of change of limb blood flow response to exercise in claudicants were significant and may have implications for the treatment of claudication.     

Stage IV micropapillary serous ovarian carcinoma: a report of three cases.

Micropapillary serous carcinomas (MPSCs) have been distinguished from typical ovarian serous borderline tumors. Although the clinical features of MPSCs have been described in several studies, there is almost no clinicopathologic information regarding stage IV MPSC patients. We describe three cases of stage IV invasive MPSC with clinical and pathologic findings. One case had an umbilical metastasis (Sister Mary Joseph's nodule), and the other two cases had cytologically positive pleural effusions. These cases demonstrate the potential of MPSCs for aggressive clinical behavior and distant metastases.