John A. Carlson

Treatment of Advanced and Recurrent Endometrial Cancer with Cisplatin, Doxorubicin, and Cyclophosphamide'

Twenty-five patients with recurrent or advanced-stage endometrial cancer were treated with cisplatin, doxorubicin, and cyclophosphamide (PAC) from May 1982 to November 1987. A retrospective chart analysis was performed to evaluate the effect of treatment on survival and progression-free interval. Toxicity was moderate. Neutropenia was the most common side effect. Age, performance status, and tumor cytoreduction were statistically significant predictors of survival time (P less than 0.03). In the 17 evaluable patients, the response rate was 47%. PAC is an active regimen in the treatment of endometrial cancer. Larger prospective studies are needed to evaluate whether tumor cytoreduction is important in the treatment of this disease.

Phase II trial of pyrazoloacridine in recurrent platinum-resistant ovarian cancer: a Gynecologic Oncology Group study.

The Gynecologic Oncology Group performed a Phase II study to determine the response rate of pyrazoloacridine (PZA) in patients with platinum-resistant ovarian cancer. PZA was administered at a dose of 750 mg/m2 intravenously over 3 hours every 3 weeks. Among 24 evaluable patients, there was 1 (4.2%) complete and 1 (4.2%) partial response. The major toxicities were hematologic. With the dose and schedule used, PZA had only modest activity in this population.

Treatment of stage II endometrial carcinoma

The optimal management of stage II carcinoma of the endometrium remains to be established. We reviewed our experience in treating 42 patients with stage II endometrial cancer by surgery, radiation, or combined radiation and surgery at the Hospital of the University of Pennsylvania. The overall 5-year survival was 47.6%. The 5-year survivals of patients treated by surgery only, radiation only, or combination radiation and surgery were 68.5, 36.5, and 46.1%, respectively, which were not significantly different. Histologic grade was found a significant prognostic factor but type of cervical involvement was not. Major complication rates were similar in each treatment group. We conclude that the majority of patients with stage II endometrial carcinoma are best treated by combination radiation and surgery, but in a select subset of patients, radical hysterectomy and lymphadenectomy constitute a reasonable treatment option.

Low-grade stromal sarcoma: DNA flow cytometric analysis and estrogen progesterone receptor data

DNA flow cytometry (FCM) data and estrogen receptor (ER) and progesterone receptor (PR) status were studied in three cases of low-grade stromal sarcoma (LGSS). One case was a primary presentation and the remaining two were recurrent tumors. DNA FCM showed a DNA index (DI) equal to 1.00, consistent with a diploid cell population, for four of the six specimens studied. The other two showed near-diploid populations. Proliferation indices (PI) were low in two of the patients tumors (8.0 and 12.7%). These findings are consistent with the clinical history of LGSS and its propensity for indolent growth, long intervals between recurrences, and generally favorable prognosis. In case 2, a patient with several recurrences, the PI was increased to 20.3% in a specimen from the first recurrence. She subsequently recurred within 1 year with a more aggressive tumor, characterized by a mitotic index of greater than 10 mitoses/10 high-power fields (HPF), absence of ER and PR, and an aneuploid population (DI = 1.19). Receptor data, obtained by dextran-coated charcoal assay, showed that all tumors except the aggressive recurrence in case 2 had high ER (average 316 fmole/mg protein) and high PR (average 753 fmole/mg protein) levels. These ER and PR data are similar to the two other reports in the literature and the usual clinical response to progestational therapy was demonstrated. Further studies will help define the possible role of FCM and ER and PR determinations in patients with LGSS. These preliminary data suggest that they may be of prognostic significance.

Cytogenetic analysis of an immature teratoma of the ovary and its metastasis after chemotherapy-induced maturation.

We report a case of an immature teratoma of the ovary, grade 3, in which cytogenetic studies were performed on the primary tumor at diagnosis and on a metastasis resected 1 year after removal of the primary tumor. The patient was treated with cisplatin, bleomycin, and etoposide (VP-16) combination chemotherapy. The metastatic tumor was composed of mature teratoma with only small foci of immature tissue. Despite the different histologic appearance of the primary tumor and the metastasis, there was no detectable difference in karyotype between the primary and metastatic tumors. Both showed a pseudodicentric chromosome derived from chromosome 1 and monosomy for chromosome 4. Flow cytometry analysis of the metastatic tumor showed a diploid DNA content, in agreement with the cytogenetic findings. From this case it would appear that chemotherapy-induced maturation of metastatic immature ovarian teratoma is not associated with regression of the malignant karyotype or selection of a karyotypically distinct population of tumor cells.

Database management for a gynecologic oncology service

With the ready availability of powerful desktop computers, the ability to manage large clinical databases has become practical. A computer can enhance the capability of a gynecologic oncology service to catalog, recall, and analyze data about patients, tumors, and therapies. While commercially available database packages can be used for this purpose, we have developed a custom database for tracking the clinical activity of a busy gynecologic oncology service. The system catalogs data about patients, admissions, tumors, and therapeutic modalities and uses this information to generate several useful reports. The reports are used for daily patient care, fellow and resident case statistics, and clinical research. What is unique about the system is that it is optimized for ease of use. The development of this tumor registry, its user friendliness, and advantages over a manual recordkeeping system are described. Unlike other tumor registries, our system is utilized on a daily basis for patient care. Therefore, the data being entered have an immediate usefulness in addition to being simultaneously added to the tumor register for retrospective clinical research. One may hypothesize that it would be useful if all gynecologic oncology services used a common computerized tumor registry that could allow for the sharing of information on a national or global scale.

The spectrum of grossly visible pigmented lesions in the uterine cervix: a prospective study.

Pigmented lesions of the uterine cervix (UC) have not been systematically studied in the literature. Over an 18-mo period, we prospectively investigated the histologic spectrum of all macroscopically visible pigmented lesions of the UC. The incidence of pigmented UC was 1.6% (33/2118). Histologic examination revealed 32 cases (97%) with a histologic correlate, of which 26 lesions were of melanocytic nature including 25 blue nevi (BNs) (81%) and 1 melanotic macule (3%). The nonmelanocytic lesions included 1 case of focal granulomatous vasculitis (3%), 2 biopsy site-associated reactive changes with hemosiderin-laden macrophages (6.4%), 1 case of hemorrhagic Nabothian cyst (3%), 1 hemangioma (3%), and 1 case of multinucleated giant cell reaction to dark black carbon-like material (3%). Women with UC BN (1.2% incidence) were mostly whites (13/25, 52%) with a mean age of 47.4 yr (range, 31–64 yr). The number and size of BN per UC, all located in the endocervix, varied between 1 to 3 and 0.1 to 2 cm (mean, 0.68 cm). UC BN exhibited 3 distinct morphologic patterns: (1) stromal melanocytic focus composed of fine spindle cells (9/25, 36%); (2) mixed pattern with fine spindle, plump spindle, and epithelioid cells (15/25, 60%); and (3) nevoid stage with epithelioid cells (1/25, 4%). In contrast, cervical melanotic macule was located in the squamous epithelium of the ectocervix and characterized by hyperpigmentation of the basal keratinocytes admixed with scattered slightly enlarged melanocytes. In conclusion, pigmented lesions of the UC are not as uncommon as reported and mostly benign in nature. Several cases may require deeper levels for their detection and to exclude the rare phenomenon of UC melanoma.

Plasmacytoid squamous cell carcinoma of the vulva.

Although neoplastic cells with a plasmacytoid appearance have been reported in a variety of tumors, to the best of our knowledge, a plasmacytoid squamous cell carcinoma (SCC) of the vulva or skin has heretofore not been described. We document the case of a 92-year-old female patient with a history of multiple excisions for vulvar verrucous and SCCs, who presented with a 3-cm, symptomatic, polypoid mass of the left upper vulva. Histologically, sheets of dyscohesive relatively monotonous plasmacytoid and spindle cells were found dispersed throughout the dermis. The neoplastic cells expressed cytokeratins AE3, 5/6, and 903, p63, and the plasma cell markers CD138 (syndecan-1) and VS38. The neoplastic cells did not label with S-100 protein, Melan-A, smooth muscle actin, desmin, Kappa and Lambda light chains, epithelial membrane antigen, MOC-31, uroplakin III, thrombomodulin, and E-cadherin. Based on the tumor location, morphology, and immunohistochemical results, the diagnosis of plasmacytoid SCC of the vulva was rendered. Six months after complete excision, she developed regional inguinal lymph node and pulmonary metastases and died. Like other plasmacytoid malignancies, vulvar plasmacytoid SCC is a rare and likely aggressive variant of SCC, which can pose significant diagnostic challenges. Squamous cell carcinoma should also be considered in the differential diagnosis of neoplasms with plasmacytoid cytology. To correctly classify plasmacytoid malignancies, a wide panel of immunohistochemical markers must be used.

Lymphocytic Arteritis in Epstein-Barr Virus Vulvar Ulceration (Lipschütz Disease): A Report of 7 Cases.

Abstract:Epstein–Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3+ CD4+ T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8+, CD20+, and CD30 + lymphocytes, CD123+ plasmacytoid monocytes, CD68+ macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.

Knowledge base as a predictor of follow-up compliance after colposcopy.

Objectives Our aim was to determine patient knowledge of cervical dysplasia and colposcopy at an inner-city obstetrics and gynecology clinic and the relationship of this knowledge base to compliance. Methods One hundred six women presenting for colposcopy at Thomas Jefferson University Hospitals obstetrics and gynecology clinic during an 8-month period were given questionnaires testing their knowledge of Papanicolaou smears, colposcopy, cervical dysplasia, and cervical cancer. Their medical records were reviewed 12 to 19 months later for patient demographics and follow-up compliance. Results Mean patient score on the nine-question test was 3.5 ± 1.7 (score range, 0–8). Answers to individual questions showed that 32.1% of patients understood the purpose of a Papanicolaou smear, 52.8% understood the nature of colposcopy, and 24.4% could identify at least three risk factors for cervical cancer. Overall compliance with planned follow-up was 54.7%. We saw no relationship between test scores and follow-up compliance. Correct answers to individual questions did not correlate with improved compliance. Age, parity, intercurrent pregnancy, and history of previous colposcopy were not predictive of compliance. Follow-up compliance correlated with the colposcopic impression of the severity of disease [79.2% for patients with high-grade lesions versus 46.9% for all others (p = .005)]. A statistical trend was observed in relation to the severity of the initiating cytological diagnosis. Conclusions Patient knowledge was poor, as demonstrated by our questionnaire. Compliance did not correlate with questionnaire scores but rather correlated with the colposcopic impression of severity of disease. Increased knowledge in patients, therefore, may not necessarily increase compliance.