James E. Wheeler

Interobserver reproducibility of histopathological features in stage II breast cancer. An ECOG study.

SummaryEleven surgical pathologists studied microscopic sections from 45 mastectomy specimens of node positive breast cancer patients who had been entered into ECOG clinical trials. Inter-observer reproducibility for histoprognostic features was examined as a prerequisite before a subsequent evaluation of their possible clinical applicability could be undertaken. Histological type, nuclear grade, tubular formation, and lymphoid reactions were studied in the cancerous tissues. Lymph nodal responses (follicular and pulp prominence, sinus histiocytosis) were also examined in a manner that simulated slide review in routine surgical pathology practice. Numerous two-way comparisons of the pathologists findings resulted in low levels of agreement (usually ≪90%). The degree of inter-observer reliability is clinically unacceptable using customary slide review analysis. New ways of examining breast cancer tissues need to be explored in the search for prognostic features which can be applied to the clinical management of breast cancer patients.

Interobserver variation in the identification of breast carcinoma in intramammary lymphatics

Nine surgical pathologists participated in a microscopic review of 35 cases of pT1-2 N0 M0 breast carcinoma. The pathologists outlined strict criteria for the identification of intramammary lymphatics and blood vessels and for the identification of cancerous emboli in these vascular channels. Each mastectomy case was studied by three different pathologists. All three concurred on the presence or absence of intralymphatic cancer in 12 of the 35 cases. Observers agreed on the absence of blood vessel invasion in 30 of the 35 cases. There was no consistent bias on the part of a single reviewer, either alone or with another pathologist, in identifying the emboli. We conclude that the identification of intralymphatic cancerous emboli in mastectomy specimens is not a reliably reproducible prognostic finding on which recommendation of systemic chemotherapy in stage I breast carcinoma patients can be based.

Epithelioid sarcoma masquerading as Peyronie's disease

A 23‐year‐old man presented with a firm plaque‐like penile mass with pain and deviation on erection, suggesting Peyronies disease. Biopsy was erroneously interpreted as confirmatory. Irradiation was the one mode of therapy which gave temporary subjective relief. Extension of the mass and focal gangrene led to rebiopsy 6 years later. Epithelioid sarcoma was present microscopically, and was also found on re‐examination of the original biopsy. Partial penectomy was performed, but pulmonary metastasis had already occurred. He was treated with chemotherapy and radiotherapy and is now alive with disease 2 years later. The diagnosis of possible penile sarcoma, although rare, must be considered in patients with symptoms suggesting Peyronies disease, especially if the lesion continues to enlarge.

Disruption of the upper female reproductive tract epithelium by nonoxynol-9

Spermicides containing nonoxynol-9 (N-9) may increase HIV transmission. In women, intravaginal N-9 is found in the uterus shortly after its insertion. Exposure of the female upper reproductive tract to N-9 may alter epithelial integrity, thereby increasing HIV transmission risk. Our goal was to characterize the histological effects of N-9 on uterine epithelium in an animal model. Female mice were exposed to intravaginal or intrauterine Advantage-S (N-9), Replens, K-Y(R) jelly or water. After various exposure times, mice were sacrificed and stained uterine tissue sections were analyzed by a pathologist blinded to treatment.Intravaginal and intrauterine N-9 administration resulted in disruption of uterine epithelium compared to Replens, K-Y jelly or water. N-9 caused rapid (within 10 min), focal, uterine epithelial sloughing and complete epithelial loss within 24 h. Epithelial regeneration began 48 h after exposure N-9 and was completely restored within 72 h; the new epithelial layer, however, was composed of cuboidal cells instead of normally present columnar cells. In addition, hemorrhage and necrosis were present are all time points examined. Our results demonstrate for the first time that N-9 has a deleterious effect on uterine epithelium. Although these results were observed in a mouse model, similar disruption of the upper reproductive tract epithelium in women by N-9 may facilitate HIV infection and serve as an unrecognized portal of human HIV transmission.

Immunostaining for carcinoembryonic antigen does not discriminate for early recurrence in breast cancer: the ECOG experience

Carcinoembryonic antigen (CEA) immunohistochemistry was evaluated by 11 surgical pathologists with sections from 147 postmenopausal women with node‐positive breast cancer. Carcinoembryonic antigen staining in breast cancer tissues has been correlated with a worse prognosis. This association was studied with a clinically characterized population of Eastern Cooperative Oncology Group (ECOG) patients using precisely the peroxidase‐antiperoxidase methodology which had been employed in another published study. In 50% of the cases, the study pathologists were uncertain whether CEA was or was not present in the cancers. Various groupings of the pathologists interpretation were compared with the observed disease‐free intervals in the patients. These analyses suggested no association of perceived CEA staining with the biological course of the cancers. Two reference pathologists who examined the sections in a similar way also gave nonprognostic interpretations. There is no convincing evidence that pathologists can reliably interpret the CEA content in the same breast cancer tissue sections. There is no observed correlation between immunohistochemical evidence of CEA in a breast cancer tissue section and the biological behavior of that cancer.

Exploratory celiotomy for cervical carcinoma: The role of histologic grading

Abstract Eighty-five patients underwent a surgical staging procedure during a 2-year period. Fifty-eight of these patients were evaluated in relation to the histologic grade of their squamous carcinoma of the cervix. An increased incidence of extrapelvic lymph node metastasis is associated with poorly differentiated tumors and with parametrial extension of the primary tumor regardless of histologic grade. Surgical staging is suggested for patients with parametrial extension of their tumor or for patients with poorly differentiated tumors.

Intralymphatic bcg in the treatment of gynecologic malignancies. A phase I study

Thirteen patients with a variety of advanced gynecologic malignancies were administered BCG via the dorsal lymphatics of the lower extremity in addition to standard accepted forms of therapy. Prolonged febrile courses, lymphangitis and suppurative adenitis were observed along the lymphatic pathway of the injected lower limbs. There was no correlation between reaction to a standard anergy panel and survival. There was also no correlation between reaction to a standard anergy panel and the inflammatory response to intralymphatic BCG (ILP‐BCG). There was, however, a positive correlation between the inflammatory response to ILP‐BCG and survival. Intralymphatic administration of immunostimulants may conceivably be of value as ancillary therapy for use in gynecologic malignancy. However, complications of this approach to immunotherapy are significant and the method should not be used until complications are decreased. Cancer 40:2933‐2940, 1977.