Antimicrobial Activity of Tebipenem and Comparators against Enterobacterales from diverse Outpatient Centers and Nursing Homes in the United States.

INTRODUCTION: Tebipenem is a potential option for the treatment of a range of infections because of its oral dosing coupled with the safety profile of the ß-lactam antimicrobial class. OBJECTIVES: To evaluate tebipenem in vitro activity against a challenge set of clinical Enterobacterales collected from outpatient and community settings. METHODS: 618 Enterobacterales isolates were submitted by 11 geographically dispersed U.S medical centers that processed cultures from affiliated outpatient centers in 2022. Susceptibility tests for tebipenem and comparator agents were performed by broth microdilution. Extended-spectrum-ß-lactamase (ESBL)-like isolates were identified phenotypically. Multidrug-resistant isolates were non-susceptible to ≥1 agent in ≥3 antimicrobial classes. Genotypic testing (CarbaR) was conducted on select isolates. RESULTS: Isolates (59% Escherichia coli) were recovered from patients seen predominantly in urology/nephrology (24%), nursing home/long-term care (21%), and ambulatory/primary care (21%) clinics. Comparator agent susceptibility rates against all isolates were as follows: levofloxacin (67.5%), amoxicillin/clavulanate (73.6%), cefixime (70.4%), cefpodoxime (70%), cephalexin (61.7%), ceftriaxone (74.4%), cefazolin (63.8%), ertapenem (97.6%), meropenem (99.7%), nitrofurantoin (64.9%), and sulfamethoxazole/trimethoprim (70.9%). Overall, 90.3% (558/619) of isolates were inhibited at a tebipenem MIC of ≤0.125 mg/L (MIC50/90, 0.016/0.125 mg/L), including 85.7% inhibition of ESBL-phenotype isolates (n=161; MIC50/90, 0.03/0.25 mg/L), 86.3% of levofloxacin and sulfamethoxazole/trimethoprim co-resistant isolates (n=95; MIC50/90, 0.016/0.25 mg/L) and 84.3% of multidrug-resistant isolates (n = 172; MIC50/90, 0.03/0.25 mg/L). Carbapenemase genes were observed in 2 ESBL-phenotype isolates with a tebipenem MIC of ≥0.5 mg/L. CONCLUSION: Relative to common oral comparators, these data demonstrate excellent tebipenem in vitro activity against Enterobacterales isolated from patients receiving care in outpatient settings, including urology clinics and nursing homes.

Metastatic HPV-related cervical adenocarcinomas presenting with thromboembolic events (Trousseau Syndrome): clinicopathologic characteristics of 2 cases.

Two cases of systemic thromboembolism (Trousseau syndrome) associated with metastatic human papillomavirus (HPV)-related endocervical adenocarcinomas are reported. The first patient, age 36, presented with bilateral lower extremity deep vein thromboses, pulmonary embolism, and supraclavicular and cervical lymphadenopathy. Lymph node biopsy revealed metastatic mucinous adenocarcinoma with focal signet ring cell differentiation. Imaging studies demonstrated metastatic disease without a defined primary site. Acute renal and respiratory failure developed and the patient expired shortly after initiation of chemotherapy, 7 weeks after presentation. Autopsy examination revealed widespread metastatic adenocarcinoma with a 2 cm cervical adenocarcinoma. The second patient, age 43, presented with left internal jugular vein thrombosis, acute thrombophlebitis, and bilateral axillary lymphadenopathy. She developed progressive venous thrombosis despite anticoagulation. Imaging studies demonstrated widespread lymphadenopathy and an adnexal mass. Diagnostic laparoscopy with biopsies and left oophorectomy revealed metastatic mucinous adenocarcinoma with signet ring cell differentiation involving peritoneum, ovary, cervix, and bladder without a defined primary site. Progressive thromboembolic disease with acute renal failure and multiple cerebral infarcts developed and the patient expired shortly after initiation of chemotherapy, 2 months after presentation. No autopsy was performed. HPV DNA was detected by in situ hybridization in the lymph node metastasis in the first case and in the cervical and ovarian tumor specimens in the second case. High-risk HPV-related endocervical adenocarcinomas occasionally exhibit signet ring cell differentiation and can present with Trousseau syndrome. These features more commonly suggest metastatic adenocarcinoma of upper gastrointestinal tract origin but the presence of HPV DNA within the tumors establishes them as cervical in origin.

A Case of Primary Melanoma of the Transverse Colon.

Melanoma is among the most prevalent neoplasms diagnosed annually with the vast majority arising from a cutaneous origin. Though there are described metastases to the gastrointestinal tract, there are only rare descriptions of primary gastrointestinal melanoma. Both diagnosis and management of this unique population can be challenging given the infrequency with which it occurs. To follow is the third reported case of transverse colon primary melanoma with a description of multimodality treatment with surgery, chemotherapy, and immunotherapy.

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.

Synchronous and metachronous endocervical and ovarian neoplasms: evidence supporting interpretation of the ovarian neoplasms as metastatic endocervical adenocarcinomas simulating primary ovarian surface epithelial neoplasms.

The vast majority of endocervical adenocarcinomas are high-risk human papillomavirus (HPV)-related neoplasms, characterized by p16 expression and frequent loss of hormone receptor expression, which infrequently metastasize to the ovaries. We report 10 cases of endocervical adenocarcinomas with ovarian metastases in which the ovarian tumors simulated primary ovarian surface epithelial neoplasms. The presence of HPV DNA was assessed to determine whether the ovarian neoplasms were metastases or independent neoplasms. Immunohistochemistry for hormone receptors and p16 was also performed. The ovarian metastases presented concurrently with the primary endocervical tumors in 5 cases, subsequent to the endocervical tumors in 3 cases, and prior to diagnosis of the endocervical tumors in 2 cases. The ovarian tumors ranged in size from 2 to 30 cm, with tumors in 7 cases measuring 10 cm or greater. The ovarian tumors were unilateral in 8 cases and bilateral in 2. In all cases, the ovarian tumors were initially diagnosed as or thought to represent independent primary ovarian surface epithelial tumors (atypical proliferative [borderline] tumors or well-differentiated carcinomas of endometrioid or mucinous type). The endocervical tumors ranged in size from microscopic foci to 3 cm, with depth of invasion ranging from 0.2 to 1.5 cm; in 2 cases, the invasive foci qualified as microinvasive according to Federation Internationale de Gynecologie et d'Obstetrique staging criteria for cervical carcinoma. Adenocarcinoma in situ was identified in all tumors. In all cases, the paired endocervical and ovarian tumors contained identical HPV types. All evaluable tumors were diffusely positive for p16; and in 8 cases, there was absent or only limited expression of hormone receptors. Two of the minimally invasive endocervical tumors were initially interpreted as adenocarcinoma in situ and not recognized as unequivocally invasive even when evaluated in conjunction with the histologically identical ovarian tumors. HPV DNA detection in the ovarian tumors of 2 patients without known cervical disease led to discovery of occult cervical adenocarcinomas in those patients. Endocervical adenocarcinomas, including some qualifying as microinvasive, can metastasize to the ovaries and simulate primary ovarian surface epithelial neoplasms. The presence of HPV DNA in these ovarian tumors confirms that they are metastatic endocervical adenocarcinomas.

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.

CD10 imunostaining does not distinguish endometrial carcinoma invading myometrium from carcinoma involving adenomyosis.

The distinction of involvement of adenomyosis by endometrial carcinoma from endometrial carcinoma invading the myometrium can at times be difficult. This distinction, however, is important from the standpoint of staging, treatment, and prognosis because the outcome of carcinoma invading the myometrium as compared with involving adenomyosis is significantly worse. CD10 has been recently reported to be expressed by normal and neoplastic endometrial stromal cells. We therefore hypothesized that CD10 may be helpful in distinguishing carcinoma within adenomyosis from endometrial carcinoma directly invading the myometrium. Twenty-two cases of invasive endometrioid adenocarcinoma were identified from the surgical pathology files of the Johns Hopkins Hospital and consultation files of one of the authors (R.J.K.) and immunostained for CD10, desmin, and caldesmon. The pattern of staining was compared with five cases in which carcinoma was confined to adenomyosis. As a control, 14 cases of adenomyosis unassociated with carcinoma were included in the analysis. All 22 endometrial carcinomas that invaded the myometrium expressed CD10 to some extent in cells immediately surrounding the neoplastic glands. In 18, all of the invasive nests displayed CD10 in surrounding cells, but in four cases the staining was patchier, involving the surrounding cells of approximately 50-75% of the invasive nests. In four cases of myoinvasive carcinoma, the CD10-positive cells surrounding the nests of invasive carcinoma were also positive for desmin and caldesmon. In the remaining 18 cases with myoinvasive carcinoma, the cells surrounding the carcinomas failed to react with desmin and caldesmon. All five endometrial carcinomas involving adenomyosis displayed CD10 positivity in what appeared to be endometrial stromal cells surrounding the neoplastic glands. The stromal cells were negative for desmin and caldesmon. The control cases of adenomyosis were all positive for CD10, although in four cases the staining was patchy compared with 10 cases in which it was diffuse. Desmin and caldesmon were negative in all of these cases. Although CD10 identifies endometrial stromal cells in the endometrium and in adenomyosis and endometriosis, this study demonstrates that CD10 does not aid in distinguishing myometrial invasion of endometrial carcinoma from involvement of adenomyosis by endometrial carcinoma because the cells surrounding the tumor in the myoinvasive group express CD10.

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.

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.

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.

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.

Lipomatous variant of angiomyofibroblastoma: report of two cases and review of the literature.

Angiomyofibroblastoma (AMF) is a rare, benign, mesenchymal tumor occurring mainly in the female genital tract. Some cases contain scattered mature adipocytes, but the lipomatous variant in which mature adipose tissue is prominent or striking is rare. Only five cases have been reported in the English literature. We report two more such cases that were composed of 70 to 80% and 30 to 40% adipose tissue, respectively. Immunohistochemical analysis showed that the tumor cells were positive for estrogen receptor, progesterone receptor, vimentin, and Bcl-2, and negative for cytokeratin AE1/1, EMA, and CD117. Tumor cells in the first case were positive for CD34 but not desmin and muscle-specific actin. The opposite expression profile of these three markers was observed in tumor cells in the second case: positive for desmin and muscle-specific actin and negative for CD34. Rare cells were positive for S-100 in adipose-rich areas in the first case. Our findings indicate that the tumor cells in the lipomatous variant have similar immunoprofile to those of usual AMF and support the concept that the lipomatous variant probably represents an extreme end of a wide spectrum of differentiation in AMF.