Presence Of Atypia Research Articles

Fine‐needle aspiration Is limited in the classification of benign breast diseases

Fine needle aspiration (FNA) has been proven to be accurate for the detection of breast carcinomas. However, its utility in the classification of benign breast lesions is less clear. We therefore undertook a study of 76 adequate preoperative FNAs of the breast from patients whose surgical biopsies of the breast were shown to be benign (18 nonproliferative diseases, 30 fibroadenomas, 19 proliferative breast diseases without atypia, and 9 proliferative breast diseases with atypia). A number of architectural and cellular features on cytology were evaluated. Histology slides were also reviewed. Both cytology and histology specimens were categorized as nonproliferative disease, fibroadenoma, proliferative breast disease without atypia, and proliferative breast disease with atypia. There was exact diagnostic correlation between cytology and histology in only 42 (55%) of the 76 cases. No cellular or architectural features on FNA examined correlated with the presence of epithelial proliferation on histology. The presence of two epithelial cell populations (one unremarkable and one atypical), small but prominent nucleoli, and nuclear pleomorphism on FNA significantly correlated with the presence of atypia on histology. However, these features are also present in breast lesions without proliferation or atypia, and are not diagnostic of atypical proliferative lesions of the breast. Therefore, FNA of the breast is limited in classifying benign breast diseases. Diagn. Cytopathol. 1998;18:56–61. © 1998 Wiley-Liss, Inc.

Melanocytic lesions and melanocyte populations in human epidermis

Basal melanocytes were counted and atypia assessed on an arbitrary scale in punch biopsies from the sun-exposed extensor aspect of the forearm of normal skin and from the covered skin of the buttock of patients with pigmented naevi and control subjects. The difference in melanocyte counts and in the presence of atypia between sun-exposed and covered skin was statistically highly significant. The only other difference was between melanocyte counts in covered skin from those with multiple atypical naevi and all other groups; the counts in the former were greater than those in the latter. No further difference was attributable to sun exposure, skin type or diagnostic group. Some degree of melanocyte atypia was seen in approximately half of the biopsies of sun-exposed skin, but atypia was seen in only six of 84 biopsies of covered skin. In each case atypia was present in the corresponding forearm biopsy and all six subjects had pigmented lesions (four with melanoma and two with multiple atypical naevi). It seems possible that while increased melanocyte counts in covered skin could correlate with the presence of atypical naevi, atypia of covered epidermal melanocytes could possibly relate to melanoma risk.

A comparison of the results of long-term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast

Follow-up information was obtained on 199 women with breast biopsy specimens containing intraductal epithelial proliferation. The proliferations were divided into regular or ordinary intraductal hyperplasia (IDH) (117 cases) and atypical intraductal hyperplasia (AIDH) (82 cases). The average length of follow-up was 14 years for the patients with IDH and 12.4 years for the patients with AIDH. Of the 117 patients with ordinary IDH, carcinoma subsequently developed in six (5%); three of these were invasive carcinomas (2.6%). All three invasive carcinomas were in the ipsilateral breast, but of the three intraductal carcinomas (IDCa), two were in the contralateral breast. Of the 82 patients with AIDH, invasive carcinoma subsequently developed in eight (9.8%); six of these were located in the ipsilateral breast and two in the contralateral breast. One of these six patients died of disseminated carcinoma. The average interval to the subsequent carcinoma (intraductal and invasive carcinoma) was about the same in the two groups (8.3 years for AIDH and 8.8 years for IDH lacking atypia). When considering only subsequent invasive carcinomas, the interval was 8.3 years for the AIDH and 14.3 years for the IDH lacking atypia. Of the 14 patients with IDH and a family history of breast carcinoma, invasive carcinoma subsequently developed in one (7%) as compared with two (2%) of the 91 with a negative family history. Among patients with AIDH, invasive carcinoma subsequently developed in two of the 13 (15%) of those with a family history of breast carcinoma as compared with one of 57 (1.8%) of the women with a negative family history. The presence of atypia in epithelial hyperplasia is a significant factor in increasing the likelihood of the development of subsequent invasive carcinoma (P = 0.03; two-tailed test). Of women with AIDH, invasive carcinoma subsequently developed in 17% of those with sclerosing adenosis (SA) as compared with 4.2% of those without it. Therefore, SA may be a contributing factor to increased risk. A positive family history also appears to increase the likelihood of the subsequent development of invasive carcinoma, particularly in patients with AIDH.

Renal Pathology in von Hippel-Lindau Disease

Von Hippel-Lindau disease, a rare autosomal disorder, is associated with multiple lesions, including a high incidence of renal lesions and CNS hemangioblastomas. Renal lesions have traditionally been classified as either benign cysts or solid renal cell carcinomas with or without cystic degeneration. We examined seven kidney specimens from four patients with von Hippel-Lindau disease. We found that renal cysts form a histopathologic continuum ranging from benign cysts (with one to two cell layers of bland epithelium), atypical cysts (demonstrating epithelial hyperplasia with or without mild cytologic atypia), to malignant cysts harboring renal cell carcinoma. The presence of atypia or foci of carcinoma does not correlate with cyst size. Lesions that appear radiologically or grossly solid range from conventional solid renal cell carcinoma, sometimes evidencing cystic degeneration, to lesions that are predominantly hyalinized, fibrotic nodules. In contrast to simple cysts occurring in the general population, which are virtually always benign, renal cysts in patients with von Hippel-Lindau disease may contain occult carcinoma. Radiologic evaluation, visual inspection at surgery, and even frozen section analysis of cyst lesions cannot be relied on to detect small foci of carcinoma. The spectrum of pathologic changes and the multicentricity of the renal lesions in von Hippel-Lindau disease complicate the radiologic evaluation and surgical management of these patients.

Renal pathology in von Hippel-Lindau disease

Von Hippel-Lindau disease, a rare autosomal disorder, is associated with multiple lesions, including a high incidence of renal lesions and CNS hemangioblastomas. Renal lesions have traditionally been classified as either benign cysts or solid renal cell carcinomas with or without cystic degeneration. We examined seven kidney specimens from four patients with von Hippel-Lindau disease. We found that renal cysts form a histopathologic continuum ranging from benign cysts (with one to two cell layers of bland epithelium), atypical cysts (demonstrating epithelial hyperplasia with or without mild cytologic atypia), to malignant cysts harboring renal cell carcinoma. The presence of atypia or foci of carcinoma does not correlate with cyst size. Lesions that appear radiologically or grossly solid range from conventional solid renal cell carcinoma, sometimes evidencing cystic degeneration, to lesions that are predominantly hyalinized, fibrotic nodules. In contrast to simple cysts occurring in the general population, which are virtually always benign, renal cysts in patients with von Hippel-Lindau disease may contain occult carcinoma. Radiologic evaluation, visual inspection at surgery, and even frozen section analysis of cyst lesions cannot be relied on to detect small foci of carcinoma. The spectrum of pathologic changes and the multicentricity of the renal lesions in von Hippel-Lindau disease complicate the radiologic evaluation and surgical management of these patients.

Repeat colonoscopy after endoscopic polypectomy.

The records of all patients undergoing endoscopic polypectomy between December 1979 and December 1982 were reviewed. One hundred seventy-two patients underwent colonoscopic polypectomy in the absence of carcinoma or inflammatory bowel disease. Of these, the polyp could not be retrieved in 4, and 19 were lost to follow-up. One hundred forty-nine patients underwent subsequent endoscopy from one to four years after the initial polypectomy. Seventy-five (50.3 percent) of the patients developed new polyps. Although 61 of the 75 patients with new polyps were identified in the first two years, new polyps were noted throughout all four years. The presence of multiple polyps on the initial examination was statistically significant in predicting new polyps. The age and sex of the patients, size of the polyps, and the presence of atypia did not identify patients at higher risk for new polyps. The data indicate that new polyps are more likely to develop in patients who had a previous polyp. It would appear that annual examinations should be performed until two successive examinations are negative. Following a second negative examination, reexamination at two- or three-year intervals, unless symptomatic, would appear to be adequate.

Methylxanthines and benign breast disease.

The relation between methylxanthine consumption and biopsied benign breast disease was investigated by using data from a case-control study which included 1,569 cases and 1,846 controls identified between 1973 and 1980 through a nationwide screening program. There was no evidence of an association between methylxanthine consumption and benign breast disease in the total study population. When histologic types of benign breast disease were examined, there were no trends in risk according to methylxanthine consumption among the 813 cases with fibrocystic disease, the 508 cases for whom detailed pathology data were not available, the 172 cases with benign neoplasms, or the 156 cases with other benign conditions. When cases with fibrocystic disease were examined according to presence of atypia, hyperplasia, sclerosing adenosis, or cysts, there was, again, no association between methylxanthine consumption and risk of disease. In addition, no relation was found between methylxanthine consumption and menstrual breast tenderness among premenopausal women with fibrocystic disease or unknown conditions.

Myxopapillary ependymoma. A clinicopathologic and immunocytochemical study of 77 cases.

The study involved 77 myxopapillary ependymomas of the spinal cord encountered during a 60-year period (1924-1983). This variant of ependymoma was, with few exceptions, limited to the lumbosacral region, particularly the filum terminale. The male:female ratio was 1.7:1, and the mean age at diagnosis was 36.4 years (range, 6-82); at presentation, 15 (19%) of the patients were in the first two decades of life. The duration of symptoms ranged from 1 month to 30 years; the most frequent complaint was low-back pain, and eight patients had undergone prior "disc surgery." Generally, myelographic block was disclosed. Preoperative cerebrospinal fluid protein levels averaged 2462 mg/dl. Myxopapillary ependymomas are slow-growing tumors that show no significant tendency to histologic dedifferentiation. Despite some variation in cytologic features and the presence of atypia and modest mitotic activity in most cases, the gross characteristics of the tumors appear to be of greater prognostic significance than the histologic features. Tumors that were encapsulated (25%) and amenable to intact, total surgical removal had a recurrence rate of 10%, whereas those that were removed either piecemeal (34%) or subtotally (41%) had recurrence rates of 19%. Overall survival, however, was more closely related to residual disease; total removal of tumor, whether intact (encapsulated) or piecemeal, resulted in longer survival (19 years) than did subtotal resection (14 years). Patients who died (6.5%) did so after a prolonged course marked by multiple recurrences. Radiotherapy may be of particular benefit to patients whose tumors are not amenable to intact total removal.

Epithelial alterations in proximity to invasive squamous carcinoma of the vulva.

The histologic changes within epithelium adjacent to invasive carcinomas theoretically may include the specific lesions that precede the development of the invasive neoplasm, or may reflect the response of host epithelium to the carcinoma or to nonspecific inflammatory stimuli related to ulceration and tissue necrosis. We have studied the vulvar epithelium surrounding squamous carcinomas of 60 women undergoing vulvectomy to determine the frequency and type of potential precursor lesions and their relationship to various biologic parameters. Using modified criteria and nomenclature of the International Society for the Study of Vulvar Disease, we identified some degree of nuclear atypia (either atypical hyperplastic dystrophy or carcinoma in situ) in 72% of patients; in only 3% was there a direct transition from normal epithelium to invasive carcinoma. There was no apparent relationship between the presence of atypia and histologic grade, depth of invasion, size or stage of tumor, or frequency of nodal metastasis. Although direct evidence is lacking, these atypical lesions may serve to identify a population at increased risk for subsequent development of invasive carcinoma.

The Management of Superficial Bladder Cancer.

Superficial bladder cancer includes tumors confined to the mucosa and lamina propria. They may be papillary or sessile. Tumors confined to the mucosa include papillomas, papillary carcinomas, or carcinoma in situ. Therapy must be individualized for each patient taking into consideration the histologic type, cytologic grade, location, number, prior history, and presence of atypia or carcinoma in situ in other areas of the bladder. Although the five-year survival rates are good (62-88 percent), the 48-70 percent incidence of subsequent tumors requires constant surveillance. This high incidence is primarily due to the multifocal origin of urothelial tumors, but implantation of tumor cells following local resection may be a contributing factor. Current efforts to reduce this recurrence rate emphasize intravesical chemotherapy. Thio-tepa and epodyl are effective in eradicating one-third of tumors when used for definitive therapy. Most studies demonstrate a reduction in the recurrence rate when they are initiated following endoscopic resection of all visible tumor. A number of other drugs are being investigated for both definitive and prophylactic intravesical chemotherapy. Surgical procedures consist of transurethral resection, transvesical radium implantation, segmental cystectomy, and cystoprostatectomy. Each procedure has its own indications, and the surgeon must be discriminating in their use.

Epithelial neoplasms of the vermiform appendix (exclusive of carcinoid). II. Cystadenomas, papillary adenomas, and adenomatous polyps of the appendix.

Forty-two cases of benign epithelial neoplasms of the appendix gleaned from the files of the Laboratory of Surgical Pathology, Columbia University, were studied. The majority were associated with dilatation of the appendix, or "mucocele." Conversely only 50% of all cystically dilated appendices examined had definite underlying adenomatous changes. Thus it is important to distinguish between cystic neoplasms (cystadenomas) and non-neoplastic retention cysts of the appendix. The most frequently found benign epithelial neoplasms were papillary adenomas. Even in the presence of atypia we labeled them benign. Appendectomy is usually adequate treatment for all adenomatous lesions occurring in the appendix. Almost a quarter of the cases reviewed were found to have synchronous or metachronous neoplasms elsewhere in the colon, while several patients harbored multiple colonic neoplasms in addition to the appendiceal adenomas. Thus a patient with an adenomatous lesion of the appendix should undergo a systematic search for other colonic lesions.

Intravascular Angiomatosis in Cutaneous Vessels

To the Editor.— The publication by Rosai and Akerman1notes the interesting and pertinent observation that vascular lesions that are probably reactive in nature may be similar to angiosarcomas histologically. These lesions, of course, must be distinguished from angiosarcoma in order to prevent unnecessary surgery or radiotherapy. On the basis of a study of a large number of organizing thrombi,2,3it seems probable to us that the lesions described by Rosai and Akerman1as intravenous atypical vascular proliferation represent peculiarly organizing thrombi, a possibility which they discussed. Masson4and Stout and Lattes5previously noted the difficulty in separating the proliferative phase of organizing thrombi from angiosarcomas. Reactive endothelial cells may exhibit striking atypia,3-5and, thus, the presence of atypia in the cases of Rosai and Akerman1is not evidence against the thrombotic origin of the lesions. Furthermore, vascular wall damage, including false aneurysm

Candida in oral leukoplakias. A histologic and exfoliative cytologic study.

Abstract— Oral leukoplakias and clinically normal mucosa of 226 patients were examined by smear or biopsy or both. From the biopsies eleven consecutive sections were evaluated, the first section being stained with hematoxylin‐eosin and the following ten with PAS. Clinically normal mucosa did not show Candida, whereas Candida was present in 31 % of the biopsied leukoplakias. Eight of the 30 Candida‐invaded biopsies did not contain the hyphae in all ten PAS‐stained sections. Had only one section been evaluated per biopsy, the risk of arriving at a false negative diagnosis was estimated to be 13 %. 40% of leukoplakia biopsies invaded by Candida showed atypia and 67 % of all atypias were associated with Candida. No relationship between intensity of Candida invasion and presence of atypia could be demonstrated.