Philip M. Dvoretsky

The Risk of Breast Cancer after Irradiation of the Thymus in Infancy

It is well established that exposure to ionizing radiation during or after puberty increases a womans risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose-response relation was linear (P less than 0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 10(4) person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life.

Distribution of disease at autopsy in 100 women with ovarian cancer

Clinical and morphologic factors that affected the distribution of disease are described in 100 cases of ovarian cancer at autopsy. In addition to the expected pattern of pelvic and abdominal peritoneal spread, extensive visceral parenchymal metastases were seen: liver parenchyma (45%), lung parenchyma (39%), small and large intestinal wall (52% and 55%), lymph nodes (70%), pancreas (21%), ureter (24%), bone (11%), and brain (6%). Liver parenchymal metastases replaced more than one third of the liver in 25% of cases, whereas lung metastases always involved less than one third of the lungs. When intestinal wall invasion was seen, bowel obstruction was present more often (71%) than when only intestinal serosa was involved (30%). Lymphatic invasion was predictive of lymph node, small intestinal wall, pancreatic, and liver as well as lung parenchymal metastases. Blood vessel invasion was predictive of pancreatic and ureteral metastases. Clinical stage I at diagnosis was associated with high incidences of liver parenchymal (56%), lymph node (56%), lung parenchymal (44%), large intestinal wall (33%), and bone (33%) metastases. Thus, ovarian cancer has parenchymal metastases similar to other carcinomas in addition to its peritoneal spread. Lymphatic and blood vessel invasion is predictive of such involvement. Intestinal wall invasion predicts bowel obstruction.

T-lymphocyte subsets in follicular lymphomas compared with those in non-neoplastic lymph nodes and tonsils

Using monoclonal antibodies on frozen sections, the authors define the anatomic localization of T-lymphocyte subsets in follicular lymphomas as well as in nonneoplastic lymph nodes and tonsils. The percentage of Leu-1+ T cells in the follicles of follicular lymphomas (20 per cent) was virtually identical to that seen in the follicles of nonneoplastic lymph nodes or tonsils (22 per cent). There were 50 per cent T cells in the interfollicular regions of follicular lymphomas and 75 per cent in the paracortical regions of the nonneoplastic specimens. In neoplastic follicles the number of Leu-3a+ cells was 67 per cent of the number of Leu-1+ cells, whereas, virtually the entire T-cell population in the nonneoplastic follicles expressed the Leu-3a antigen. These T cells of helper phenotype may facilitate the neoplastic process or an immune response against it or may be bystanders to the B-cell proliferation. Hum Pathol 13:618-625, 1982

Morbidity and recurrence with modifications of radical vulvectomy and groin dissection

Vulvar carcinoma has been managed in recent years with modifications of radical vulvectomy and groin dissection. Separate groin incisions, superficial inguinal lymphadenectomy, unilateral groin dissection, and wide excision have been utilized to reduce the morbidity of treatment. In this study, the surgical management of 82 patients with vulvar squamous cell carcinoma was reviewed in order to assess morbidity and risk of recurrence. A modification of radical vulvectomy and groin dissection was employed in 67 patients, while 15 patients underwent classical en-bloc vulvar and groin dissection. Wound complications of the vulva occurred in 1 of 12 patients undergoing hemivulvectomy, in 8 of 55 undergoing radical vulvectomy, and in 7 of 15 who had en-bloc vulvar resection and groin dissection (P = 0.01). Among the 46 patients undergoing bilateral groin dissection through separate incisions, groin breakdown, lymphocyst, and lymphedema occurred in 10 (22%), 7 (15%), and 7 (15%), versus 0, 1 (7%), and 2 (13%) of the 15 who had unilateral groin dissection. Modification of vulvar resection did not increase the risk of local recurrence. Groin recurrence developed in 2 of 15 patients who underwent en-bloc groin dissection and in 1 of 46 who underwent bilateral groin dissection through separate incisions. Two of 15 who had a unilateral groin dissection recurred in the contralateral groin. The risk of recurrence as well as morbidity following modifications of radical vulvectomy with groin dissection should be considered when planning treatment.

Survival time, causes of death, and tumor/treatment-related morbidity in 100 women with ovarian cancer

One hundred cases of ovarian cancer were studied at autopsy to determine the effect of morphologic and clinical factors on survival time, the primary cause of death, and tumor/treatment-related morbidity. The mean survival time was 19 months (0 to 174 months). Increasing neoplastic histologic grade and increasing clinical stage at diagnosis were each associated with decreased survival time. In grade I tumors, the mean survival time was 84 months; in grade II tumors, it was 18 months; and in grade III tumors, it was 12 months (P = .0008). Patients who presented in stage I or II had a better survival time (28 months) than those who presented in stage III or IV (15 months) (P = .02). The most common causes of death were disseminated carcinomatosis (48%), infection (17%), pulmonary embolus (8%), and combinations of infection and carcinomatosis (11%). In patients dying of infection, 43% had sepsis, 21% had pneumonia, and 25% had a combination of sepsis and pneumonia. Escherichia coli and Klebsiella were the most common pathogens identified postmortem. Intestinal obstruction (51%) and ureteral obstruction (28%) were the most common forms of tumor-induced morbidity. Bone marrow depression and resultant pancytopenia was the most common form of treatment-induced morbidity.

Treatment of breast cancer with segmental mastectomy alone or segmental mastectomy plus radiation

A retrospective review of the outcome of treatment for primary, Stage I and II breast cancer with segmental mastectomy (SGM) alone or segmental mastectomy plus postoperative irradiation (SGM + RT) at four Rochester, New York, city hospitals is reported. Between January 1971 and March 1984, 99 women were treated with SGM and 146 with SGM + RT. Groups were similar regarding significant clinical and histologic prognostic factors; they differed, however, in that the SGM group was considerably older (means = 72) than the SGM + RT group (means = 56). Among SGM patients, local and total locoregional failure was 26.44 and 35.2%, respectively. Local and total locoregional failure (7.6 and 12.4%, respectively) was significantly reduced among patients treated with SGM + RT (p less than 0.0001). Among SGM patients, there was scant advantage in enlarging the extent of resection from local excision (29.5% local failure) to wide local excision (27.3%) to quadrantectomy (22.2%). Among women receiving SGM + RT, similar rates of local failure occurred among patients receiving local excision (15.5%) and wide local excision (12.5%). By contrast, only 2.8% of those receiving quadrantectomy failed. Results are viewed as supportive of findings of NSABP-B06. Findings suggest that SGM constitutes inadequate treatment of Stage I and II breast cancer. Locoregional failure rates of 30-40% may be reduced to around 10% with postoperative irradiation.

The pathology of breast cancer in women irradiated for acute postpartum mastitis

The gross and microscopic pathology of breast cancers in women irradiated for acute postpartum mastitis was compared to the breast cancers found in the sisters of the irradiated women. Fifty‐one cancers in 50 irradiated women and 25 cancers in 24 nonirradiated women were examined. In considering the lesions in the two populations, the size, location, histologic type, histologic grade, inflammatory response, lymphatic and blood vascular invasion, nipple involvement, axillary lymph node metastases, and menopausal status at the time of diagnosis were statistically indistinguishable. The only parameter that was different in the two populations was the desmoplastic response to the malignant lesion (P = 0.04). The control population had more marked fibrosis within the cancers compared with the irradiated women. With the exception of stromal response, this study shows that breast cancer in irradiated women is similar in the parameters evaluated to breast cancer in a control population.

Endometrial carcinoma: The relevance of cervical cytology

In patients with endometrial carcinoma, preoperative identification of poor prognostic factors is helpful in planning therapy. Extended surgical staging, including pelvic and periaortic node dissection, is indicated in patients with deep myometrial invasion or high-grade tumor, or when other risk factors for extrauterine spread are present. In this study, cervical cytology was reviewed in 86 patients with endometrial carcinoma, all of whom underwent surgical staging, to correlate the cytologic results with surgical and pathologic findings. Cervical cytology was normal in 20 patients (23%), whereas suspicious or malignant endometrial cells were present in 23 and 43 cases (27 and 50%), respectively. Suspicious or malignant cervical cytology was associated with deeper myometrial invasion (P=.011), higher postoperative tumor grade (P=.006), positive peritoneal washings (P=.012), and more advanced stage by International Federation of Gynecology and Obstetrics criteria (P=.024). When compared with patients with normal cervical cytology, those who had malignant endometrial cells had over twice the risk of deep myometrial invasion (67 versus 30%), twice the risk of grade 2 or 3 tumor (60 versus 30%), and three times the risk of positive peritoneal washings (33 versus 10%). Seventy-four percent of patients with malignant cervical cytology were stage IC or more. In contrast, 70% of patients with normal cervical cytology were stage IA or IB. Patients with endometrial carcinoma who have malignant endometrial cells detected by cervical cytology are at increased risk of having a deeply invasive, high-grade, advanced-stage tumor, and therefore are more likely to require extended surgical staging

The Pathology of Superficially Invasive, Thin Vulvar Squamous Cell Carcinoma

Thirty-six cases of vulvar squamous cell carcinoma 5 mm or less in thickness were studied, and potential predictors of lymph node metastases were evaluated. Tumor thickness and depth of stromal invasion were measured. Inguinal lymph node metastases were present in six (17%) cases, all of which had primary neoplasms more than 3 mm thick. The most superficial lesion to have lymph node metastasis was 3.2 mm thick and had 1.6 mm of stromal invasion. Nonetheless, depth of stromal invasion of less than 3 mm was associated with statistically fewer lymph node metastases (7%) than that of neoplasms with 3 mm or more of stromal invasion (50%). Although lymphatic or blood capillary invasion was present in four (11%) cases, this feature had no statistically significant association with lymph node metastasis. There was no relationship between clinical stage, surface diameter, or histological grade of the lesion and lymph node metastasis. A significant percentage of cases had either carcinoma in situ (31%) or atypical hypertrophic dystrophy (19%) in the epithelium adjacent to the infiltrating carcinoma. Koilocytotic atypia suggestive of human papilloma virus infection was present in the adjacent epithelium in 47% of the cases. This study suggests that thickness of the neoplasm is a valid predictor for the presence or absence of lymph node metastasis in vulvar squamous cell carcinoma; it may be more useful than neoplastic depth of invasion in this regard.