Subsequent Carcinoma Research Articles

Laryngeal keratosis and subsequent carcinoma

The frequency with which carcinoma develops in laryngeal keratoses is a controversial subject. A study of 92 cases of laryngeal keratosis with a minimum of five years' follow-up resulted in identification of three patients (3.26%) who developed laryngeal carcinoma. A reviews of the literature reveals that, in series of keratoses defined by stringent pathologic criteria, subsequent laryngeal carcinoma develops in 3.33%-4.31%. These findings support a low but predictable frequency of conversion to malignancy in laryngeal keratosis. A grading system for keratosis is presented and discussed with reference to clinicopathologic correlation.

Serial Transplantation of Chemical Carcinogen-Induced Mouse Mammary Ductal Dysplasias<xref ref-type="fn" rid="fn2">2</xref>

BALB/c and (C57BL times DBAf)F1 mice were treated with 7,12-dimethylbenz[a]anthracene and urethan, respectively, to induce mammary dysplasias. Nine transplantable outgrowth lines of dysplastic tissue were established by transplantation of the primary lesions into the cleared mammary fat pads of syngeneic mice; 8 of the 9 lesions were ductal in origin. The growth and tumorigenic potentials of these 9 lines were followed over 6-9 transplant generations. Most outgrowth lines exhibited a rapid decline in growth potential and/or a progression to papillomatosis and subsequent carcinoma by transplant generation 7. The ductal outgrowth lines and mammary tumors established from urethan-induced dysplasias in hybrid mice were ovary-dependent for tumorigenesis and tumor growth. The transplantation experiments confirmed the hypothesis that ductal dysplasias have high tumorigenic potentials and can be classified as "high-risk" lesions, similar to murine mammary tumor virus-induced hyperplastic alveolar nodules.

Multiple carcinomas following therapy for Hodgkin disease

A 52-year-old man developed synchronous squamous-cell carcinoma of the larynx and middle one-third of the esophagus following treatment of Hodgkin disease. This patient fell into the subgroup of patients treated by intensive radiation therapy followed by intensive chemotherapy. The link between the therapy and subsequent carcinoma is suggestive. Long-term follow-up care of patients with Hodgkin disease demands continuing evaluation of this possible complication.

Relation Between Component Parts of Fibrocystic Disease Complex and Breast Cancer<xref ref-type="fn" rid="FN1">2</xref>

Specimens of benign breast disease obtained from biopsies performed at Vanderbilt Hospital (Nashville, Tenn.) between 1952 and 1959 were histologically reviewed and characterized as to individual component types of fibrocystic disease. Follow-up for information regarding breast cancer development was 94% successful. Carcinoma developed more often when epithelial proliferative lesions were present. Atypical lobular hyperplasia had a greater predictive value than other epithelial lesions and was associated with an elevated risk six times that expected prior to the age of 45 years and a tripling of risk after the age of 45 years. Various ductal hyperplastic lesions are associated with approximately a doubly increased risk that is present only if the lesions are identified at biopsy after the age of 45 years. Women with cysts, sclerosing adenosis, fibrosis, and other nonhyperplastic changes were at no greater risk for subsequent carcinoma than women in the general population.

Lobular carcinoma in situ of the breast Detailed analysis of 99 patients with average follow-up of 24 years

Ninety-nine patients with in situ lobular carcinoma (LCIS) of the breast, not treated by mastectomy, were identified in a review of consecutive breast biopsies performed at Memorial Hospital between 1940 and 1950. Follow-up for an average of 24 years was obtained in order to determine the frequency of subsequent breast carcinoma. Detailed analysis of important clinical and pathologic features was undertaken to identify predictive factors that would serve to distinguish between patients with the greatest and least risk for subsequent carcinoma. Thirty-nine breast carcinomas other than the original LCIS were diagnosed in 32 patients. Half of the carcinomas occurred in the same and half in the opposite breast. The hazard rate for subsequent carcinoma increased with increasing length of follow-up and increasing age. When compared with general population data, the frequency of subsequent breast carcinoma was nine times greater than expected and deaths due to breast carcinoma were 11 times more frequent than expected. None of the currently recommended choices for therapy is entirely satisfactory. Follow-up without further surgery should be considered an investigative procedure until more information is available. This recommendation should be made only if the patient and physician are prepared to accept the responsibility of lifetime surveillance. At present, we consider it prudent in most cases to recommend ipsilateral mastectomy with low axillary dissection and concurrent biopsy of the opposite breast. Contralateral mastectomy is most appropriate when carcinoma is detected in the biopsy.

Lobular neoplasia (so-called lobular carcinoma in situ) of the breast

In a review and reclassification of 5,560 benign epithelial lesions of the breast entered in the files of the Laboratory of Surgical Pathology at Columbia, we found 211 examples of the type of lobular proliferation occurring alone without co-existing infiltrating carcinoma, which we prefer to call lobular neoplasia, but which is generally referred to as noninfiltrating lobular carcinoma in situ. We regard this lesion as a separate distinctive pathological-clinical entity. These 211 cases are studied from a number of parameters, including the ages of the patients, the breast affected, the length of the follow-up, the interval between the initial diagnosis and the frank carcinoma which eventually developed in 17.1 percent of the patients. The relationship of microscopic qualitative and quantitative variations in the lobular neoplasia to subsequent carcinoma was studied; the variations were not found to have any value in predicting subsequent carcinoma. This study is unique in that we have data as to the frequency of a family history of carcinoma in a mother or sister, and also as to the occurrence of gross cystic disease in our patients with lobular neoplasia. We have determined the ratio between the observed and expected numbers of patients developing carcinoma in the several possible combinations of these three factors which predispose to carcinoma. We report that the predisposition is cumulative: in patients in whom all three predisposing factors were present the ratio of observed to expected risk of carcinoma was 13:8. We do not recommend mastectomy for lobular neoplasia, but only systematic follow-up by palpation of the patients' breasts every four months.

Intraductal carcinoma. Long-term follow-up after treatment by biopsy alone

A follow-up period averaging 21.6 years was obtained for patients with low-grade papillary intraductal carcinoma initially treated only by biopsy between 1940 and 1950. Subsequent carcinoma was diagnosed in the same breast in seven of the ten patients after an average interval of 9.7 years. Six of the seven subsequent carcinomas were invasive. Two of the patients died of metastatic carcinoma and two were known to be alive with metastases when last contacted. Three patients were without carcinoma following mastectomy. When these results were combined with the few reports available in the literature, it appeared that at least 39% of patients with intraductal carcinoma treated by biopsy alone subsequently had clinically evident carcinoma, invariably in the same breat, with an average latent period of about ten years. This was undoubtedly a result of the multicentric nature of the disease in many patients.

Recurrent urothelial tumors following surgery for transitional cell carcinoma of the upper urinary tract

A retrospective analysis of 74 cases of transitional cell carcinoma of the renal pelvis and ureter treated at this institution over the past 30 years is presented. When nephrectomy alone or incomplete nephroureterectomy was performed, subsequent transitional cell carcinoma developed in 30% of the ureteral stumps. Subsequent bladder carcinoma occurred in 25% of the patients with primary upper urinary tract carcinoma. The type of initial surgery performed did not appear to influence this incidence of subsequent bladder tumors. Contralateral upper urinary tract carcinoma developed in only one patient. When nephroureterectomy is performed for carcinoma of the renal pelvis and ureter, a cuff of bladder that includes the ureteral orifice should be removed to obviate recurrent disease in the ureteral stump. Since single-incision nephroureterectomy did not include the intramural ureter in 50% of the cases in which it was performed, a second incision may be required for adequate exposure.

Incidence of Multiple Primary Cancers. IV. Cancers of the Female Breast and Genital Organs

The incidence of multiple primary cancers of other organs or tissues was studied in patients with carcinomas of the breast (9,792), ovary (921), endometrium (843), and cervix uteri, vagina, or vulva (2,529). The index patients were treated during 1949–62 at the Memorial Sloan-Kettering Cancer Center, and their observed frequency of new primary cancers was compared with the age- and site-specific incidence rates reported by the population-based central registry maintained for New York State (excluding New York City). The incidence of metachronous primary carcinomas in the opposite breast was 6.1/year/1,000 patients, or 4.5 times expectation; in the patients with carcinoma of the breast, the incidence of multiple primary carcinomas of the ovary was 0.6/year/1,000 patients, or twice the normal risk, but one-tenth the risk for incurring a primary carcinoma in the opposite breast. The risk for incurring a metachronous primary carcinoma of the breast by a patient with a previous ovarian carcinoma was 3–4 times the normal risk. In patients with endometrial carcinoma, the risk of a subsequent breast carcinoma was 1.25–2.0 times the normal risk. The demonstration of a positive association of multiple primary carcinomas of the breast, ovary, and endometrium suggests demographic characteristics and etiologic factors common to these diseases. At least 3 of the 5 observed multiple, primary, soft-tissue sarcomas developed as sequelae of previous breast cancers—1 arising in irradiated tissue and 2 in a lymphedematous upper extremity. We could not conclude whether the mutual increases in the incidence of carcinomas of the breast and thyroid were biologically related or were indicative of common etiologic factors.

Laser effect on DMBA-induced dyskeratoses of the hamster cheek pouch.

Results of 21 months of experimental investigation of 120 Syrian hamsters with 9, 10 dimethylbenz (a) anthracene-induced dyskeratoses and subsequent papillomas and squamous-cell carcinomas, and the reaction to treatment of pulsed ruby laser are presented. In addition, tentative results of experiments with continuous argon-ion laser radiation are presented and histopathology of the lesions is reported. Conclusions are given involving statistical analysis of the data which strongly support the hypothesis that pulsed laser radiation has an inhibitory effect on tumor growth, reducing the rate of cell division. On the basis of this work, it is postulated that an approximately eightfold reduction in mitotic rate in hamster oral tumor growth occurs, along with a decrease of incidence of tumor formation to approximately one half of control results.

Carcinoma of the cervix in American Indian women.

The frequency of cervical carcinoma as indicated by suspicious cervical cytologic smears and biopsy results is reported for Southwestern Indians and Caucasian residents of New Mexico, matched as closely as possible for age and socio-economic level. Despite conditions of poverty, multiple pregnancies, early coitus, and uncircumcised consorts, Southwestern Indian women apparently have a lower rate of cervical carcinoma than age-matched Caucasian controls. The lower frequency of cervical carcinoma found in Indians is interpreted to be at least partly the result of delay in first births relative to Caucasians in the study population. Evidence is presented that delay in first pregnancies among Indians is not due to cultural factors but to a period of transient adolescent sterility. In our study population, age at first childbirth seems to be a more significant determinant of subsequent cervical carcinoma than age at first coitus.

Can breast carcinoma be anticipated? A follow-up of benign breast biopsies.

110 women who had undergone biopsy for benign lesions of the breast were studied for subsequent development of breast carcinoma over the following 16-20-period. 10 women in the study developed carcinoma in the same or opposite breast within 16-20 years, a rate of incidence 480% greater than among the general population of women of the same age. Average interval time from biopsy to appearance of malignant tumors was 9 years. The original biopsies were studied and categorized with a view to isolating pathologic factors which might indicate high risk. No factor could be associated with subsequent carcinoma development. The incidence of carcinoma appeared related to years of risk only. It is recommended as a result of this study that all women who undergo biopsies for benign breast lesions should have life-long followup since they seem to be at high risk.

Histological effects of progestins on hyperplasia and carcinoma in situ of the endometrium—Further observations

Twenty-three patients with cystic and adenomatous hyperplasia and 8 patients with carcinoma in situ of the endometrium were treated with progestogens after excluding invasive carcinoma by thorough uterine curettage. All patients were in the menopausal or postmenopausal age group. In each case glandular atrophy and stromal decidua were produced and in one-third the patients there was evidence of residual hyperplasia with “drug effect” by the progestogenic agent. In no instance did subsequent invasive carcinoma occur.

Extensive Lupus Erythematosus with Subsequent Carcinoma of Lower Lip

Extensive Lupus Erythematosus with Subsequent Carcinoma of Lower Lip

The Relation of Pregnancy to Carcinoma of the Uterus

Carcinoma of the cervix occurs more often in married women who have borne children than in any other class. The trauma incident to childbirth and the after effects on the cervix have been considered to be the exciting cause, by most observers. Cullen (1) reported a series of 50 squamous cell carcinomas of the cervix in married women. One was a nullipara. At least half had borne five or more children. He also reported 13 cases of adenocarcinoma of the cervix, 12 of which occurred in married women who had been pregnant. Kelly (2) states that there is no doubt that the injuries inflicted upon the cervix uteri during labor are a definite causal factor in subsequent cervical carcinoma. 98 per cent of the women with squamous cell carcinoma of the cervix in his clinic at the Johns Hopkins Hospital had borne children. Ross (3) reported 475 cases of cancer of the uterine cervix. All except 11 were married and the average number of children was four. Most statistics dealing with carcinoma of the cervix show a similar marked preponderance of parous women, but in some reports the preponderance is not so great. Pomeroy and Strauss (4) in a study of 100 cases of carcinoma of the cervix uteri found that 10 per cent of their patients had not been pregnant. Healy (5) reported 149 cases with carcinoma of the cervix, 144 married and 5 single. The 5 single women and 12 of the married women had never been pregnant.