Initial Excisional Biopsy Research Articles

Superficial cervico-vaginal myofibroblastoma: a report of five cases

To describe the pathological and immunohistochemical features of five cases of superficial cervico-vaginal myofibroblastoma (SCVM), a recently described mesenchymal tumour affecting middle-aged and elderly females. The histological features of five cases of SCVM arising in four patients were reviewed including one case which recurred locally 9 years after initial excision biopsy. All cases were immunostained using the streptavidin-biotin technique using antisera to vimentin, smooth muscle actin, desmin, S100 protein, cytokeratin, h-caldesmon, calponin, CD99, CD117 (c-kit), bcl-2, oestrogen receptor and progesterone receptor. The patients were aged from 40 to 71 years (mean 55.2 years). The tumours were situated within the vagina (four cases) and cervix (one case) and ranged from 16 to 45 mm in greatest dimension. One patient had two separate vaginal SCVM. The tumours were characterised by uniform spindle and stellate-shaped cells separated by a collagenous or myxoid stroma. No mitotic activity was identified. Characteristically the tumours were well circumscribed and separated from the surface epithelium by a rim of normal stroma. The initial and recurrent tumours in one patient were similar except for increased stromal collagen in the recurrence. All tumours were immunoreactive for vimentin, desmin, CD34, CD99, bcl-2, calponin and hormone receptors while two tumours showed focal smooth muscle actin expression. There was no expression of S100 protein, h-caldesmon, CD117 or cytokeratin. SCVM appears to be a relatively distinct lesion although there is some histological and immunophenotypical overlap with other mesenchymal tumours, particularly fibroepithelial polyp, leiomyoma and solitary fibrous tumour. As local recurrence developed 9 years after intial treatment in one patient, long-term clinical follow-up would seem appropriate.

Intraductal papilloma with “comedo-like” necrosis, a diagnostic pitfall

Necrosis in the breast is more frequently associated with malignancies than benign conditions. In the latter, it may be diffuse as seen in infarcts, postpartum changes, and after anticoagulant therapy, or focal as in florid adenosis and juvenile papillomatosis. The goal of this study was to find other benign entities associated with necrosis. Using our pathology database from January 1994 to March 2003, we identified 10 cases of florid duct hyperplasia associated with luminal necrosis. Clinical information was collected and all slides were reviewed. The age of the patients ranged from 36 to 94 years (mean, 53.2 years). All patients underwent an initial excisional biopsy except for one who had a core biopsy. Patients presented with a palpable mass (6 cases) a radiographic density (3 cases), or nipple discharge (1 case). Findings correlated with the presence of an intraductal papilloma with adjacent or associated florid duct hyperplasia. Within the central luminal spaces of the florid duct hyperplasia, cellular debris associated with necrosis was present and was morphologically identical to that seen in comedo intraductal carcinoma. In fact, in two of the four consultation cases, these lesions were initially diagnosed as comedo carcinoma. Re-excision performed in three cases showed no atypia or malignancy. It is important to recognize the presence of comedo-like necrosis in florid duct hyperplasia associated with or adjacent to intraductal papillomas of the breast and not to misinterpret these findings as intraductal carcinoma. The necrosis may be secondary to reactive changes within the intraductal papilloma.

Clinical Behavior and A Contemporary Management Algorithm for Prepubertal Testis Tumors: A Summary of the Prepubertal Testis Tumor Registry

The Prepubertal Testis Tumor Registry was established by the Urologic Section of the American Academy of Pediatrics in 1980 to record data on a large number of prepubertal testis tumors regarding presentation, treatment and outcome to define appropriate management better. We reviewed the registry data in the context of other modern studies to elucidate the appropriate management of these rare tumors.Relevant data in the prepubertal testis tumor registry were tabulated and analyzed.There were 395 prepubertal patients who had a primary testis tumor. Generally benign tumors accounted for 38% of cases. A significant proportion of tumors were benign regardless of patient age. alpha-Fetoprotein levels for patients with benign and malignant tumors overlapped in children younger than 6 months. Of the patients with yolk sac tumor 80% presented with stage 1 disease and overall survival was excellent. There were no metastases or deaths among the patients with teratoma. Of all patients with stromal tumors metastases developed in only 1.We recommend initial excisional biopsy for all amenable prepubertal testis tumors, except those with an alpha-fetoprotein level that is clearly increased for patient age. Patients with benign tumors may be released from oncological followup. Patients with stage I yolk sac tumor should be monitored closely, and those with recurrent or metastatic yolk sac tumor should be treated with chemotherapy. Retroperitoneal lymph node dissection is reserved for patients with recurrent retroperitoneal masses following chemotherapy. Aggressive treatment of metastatic Sertoli cell or undifferentiated stromal tumors is warranted.

Pathologic features of initial biopsy specimens associated with residual intraductal carcinoma on reexcision in patients with ductal carcinoma in situ of the breast referred for breast-conserving therapy.

The histologic criteria for determining which patients require a reexcision after an initial excisional biopsy for ductal carcinoma in situ (DCIS) of the breast are poorly defined. The authors examined the initial biopsy specimens of 98 patients with inked margins and determined the amount of DCIS on reexcision to help clarify which histologic criteria are useful in judging the need for reexcision. Features in initial biopsy specimens that were associated with an increasing number of slides with DCIS on reexcision were an increasing number of slides with DCIS, an increasing number of DCIS ducts or terminal duct lobular units (TDLUs) with "cancerization" of lobules (COL) within 0.42 cm of the inked margin, and multifocal positive margins. In patients with negative (>0.2 cm) initial biopsy specimen margins, an increasing number of DCIS ducts or TDLUs with COL near the initial biopsy specimen margin were also associated significantly with an increasing number of slides with DCIS on reexcision. Six or more slides with DCIS or 11 or more DCIS ducts or TDLUs with COL within 0.42 cm of the inked margin in the initial biopsy specimens were associated with 6 or more slides with DCIS on reexcision. These results suggest that the amount of DCIS in initial biopsy specimens and the amount of DCIS near the margin are associated with the quantity of DCIS remaining in the breast after an initial excisional biopsy. Pathologists can use these factors when assisting clinicians in evaluating the need for a reexcision.

The unsatisfactory margin in breast cancer surgery

Background: Surgical margin involvement with breast cancer usually results in obligatory reexcision or mastectomy. While unalterable occult host and pathologic factors may interfere with margin clearance during the initial excision, it is possible that alterations in surgical technique might increase the likelihood of obtaining satisfactory margins. Methods: Two hundred and thirty-five patients who were candidates for breast conservation therapy were identified for 1991 and 1996 using the Tumor Registry. Margins were defined as “unsatisfactory” if there was microscopic involvement with tumor or the margin was close at initial excisional biopsy and the surgeon opted for reexcision. Multiple logistic regression analyses of factors associated with margin status were performed. Results: One hundred thirty-two (56%) patients had positive or close (unsatisfactory) margins; this rate increased from 51% in 1991 to 59% in 1996. Patients with unsatisfactory margins underwent more procedures (mean 2.0 versus 1.2; P <0.0001) than patients whose margins were satisfactory. The breast conservation rate for patients with unsatisfactory margins was 64% compared with 99% for patients with satisfactory margins. A multiple logistic regression demonstrated that patients with unsatisfactory margins were 67 times more likely to have a mastectomy than patients whose margins were satisfactory after adjusting for other significant factors ( P <0.0001). The practice of fine needle aspiration biopsy, orientation of specimen margins by the surgeon, and reexcision of tumor at the first operation were statistically significant technical factors in obtaining satisfactory margins. Significant pathology factors were extensive intraductal component (EIC), lobular or ductal extension, and tumor size. Conclusion: These data show that technical factors in the surgical management of breast cancer, as well as biological factors such as EIC, can influence the success of breast conservation.

30 Gy may be an adequate dose in patients with anal cancer treated with excisional biopsy followed by combined-modality therapy.

There are a subset of patients with invasive anal cancers who undergo an excisional biopsy either before or after combined-modality therapy (CMT). The objective of this study is to determine whether these patients can be adequately treated with a lower dose of pelvic radiation therapy. A total of 25 patients were treated with CMT either before or after an excisional biopsy. The four subsets included 8 patients with initial excision followed by CMT with 30-34 Gy (EX/30), 6 patients with initial excision followed by CMT with 45-50.4 Gy (EX/45), 10 patients treated by CMT with 30 Gy followed by an excision (30/EX), and 1 patient by CMT with 45 Gy followed by an excision (45/EX). For the total group, the actuarial 5-year disease-free survival was 78%, overall survival was 86%, colostomy-free survival was 91%, and local control was 82%. When patients received CMT either before or following an excision, the actuarial local control and survival results with 30-34 Gy vs. 45-50.4 Gy were similar. In contrast to radiation dose, in patients who received 30-34 Gy, the sequence of the excision (before or after CMT) did appear to have a borderline significant impact on local control. Actuarial 5-year local control was 100% for EX/30 vs. 67% for 30/EX (P = 0.08). Because of the small number of patients in each group and the retrospective nature of the analysis, it is difficult to draw definitive conclusions from this study. However, our data suggest that in patients who are selected to undergo an initial excisional biopsy followed by CMT, 30 Gy may be an adequate radiation dose. Local control may be higher in patients who undergo an excisional biopsy followed by CMT compared with the converse.

Use of touch preps for diagnosis and evaluation of surgical margins in breast cancer.

The best cosmetic results with conservative breast surgery are obtained at the time of initial excisional biopsy. The usefulness of the touch prep (TP) technique was evaluated for accuracy in diagnosis as well as in evaluation of margins at the time of original breast biopsy. Four hundred twenty-eight consecutive patients with breast masses seen from January 1993 to December 1994 were evaluated prospectively using TP. Three hundred forty-five benign and 83 malignant tumors were evaluated. Tumors ranged in size from microscopic to 8 cm. Pathologic diagnosis was correct as compared to permanent section in 99.3%. The three carcinomas missed on TP were focal and in situ. Sensitivity was 96.39%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 99.3%. For margin evaluation, the sensitivity and specificity were both estimated to be 100%. TP has the advantage of being a simple, quick (2 to 3 minutes), safe (no loss of diagnostic material), and accurate method for diagnosis and estimation of tumor margins at the time of the original surgery.

Breast carcinoma: MR imaging before re-excisional biopsy.

To investigate the role of magnetic resonance (MR) imaging in the examination of patients after excisional biopsy of breast carcinoma before re-excision. Forty-seven patients underwent contrast material-enhanced MR imaging after initial excisional biopsy of breast carcinoma before further surgery. The positive predictive value of MR imaging for predicting residual disease was 82%; the negative predictive value was 61%. Fourteen patients had multifocal (n = 6) or diffuse (n = 8) carcinoma. The extent of tumor was correctly identified with MR imaging alone in nine of the 14 patients, with both mammography and MR imaging in three patients, with mammography alone in one patient, and with no imaging modality in one patient. In four of the 14 patients, management was altered from re-excision to mastectomy (n = 3) or from breast-conservation therapy to mastectomy (n = 1). MR imaging has a high positive predictive value for predicting residual tumor after excisional biopsy. The identification of mammographically and clinically unsuspected multifocal or extensive residual tumor may lend support for mastectomy rather than re-excision. However, false-negative findings due to postsurgical changes and false-positive findings due to enhancement of granulation tissue and benign breast tissue remain limitations.

Factors associated with a positive reexcision after excisional biopsy for invasive breast cancer

Breast-conserving therapy followed by adjuvant radiotherapy represents an alternative to mastectomy as a treatment for invasive breast cancer. When excisional biopsy has been performed outside the parent institution, reexcision is often performed, with tumor being identified in 32% to 62% of the subsequent specimens. We analyzed not only the factors associated with a positive reexcision but also those factors associated with final surgical margins that are positive for tumor. Between 1978 and 1991, 956 female patients with American Joint Committee on Cancer clinical stage I or II breast cancer were treated with breast-conserving therapy where a total of 420 patients underwent reexcision after an initial excisional biopsy. Several factors were analyzed to determine their association with a positive reexcision, the status of the final surgical margin, and the nature of the disease present within the reexcision specimen. Factors that correlated with a positive reexcision in both univariate and multivariate analysis were clinical tumor size, method of detection, the pathologic status of the axillary lymph nodes, and the histologic appearance. Those factors associated with finding invasive disease at the time of reexcision were clinical tumor size, clinical presentation, and nodal status. The single factor associated with finding residual in situ disease at the time of reexcision was histologic appearance of the primary tumor. A final positive margin was associated with method of tumor detection, age of the patient, and the presence of axillary lymph node metastases. The most significant factors associated with a positive reexcision are clinical tumor size, method of tumor detection, pathologic nodal status, and histologic appearance. Patients with larger tumors or those that are detected by physical examination, as well as invasive lobular carcinomas, may require a more generous initial resection to achieve negative surgical margins and avoid the likelihood of reexcision.

Conservative surgery and radiation therapy for infiltrating lobular carcinoma of the breast: The role of preoperative mammograms in guiding treatment

The authors have reviewed their institution's experience with conservative surgery and radiation therapy for early stage breast cancer with the goal of defining the impact of infiltrating lobular histology (ILC) on the local recurrence rate. Also, they have examined the preoperative mammograms of the ILC patients to determine if mammographic features could be used to predict treatment outcome. Between January 1, 1980, and December 31, 1987, 402 cases of Stages I and II breast cancer were treated with conservative surgery and radiation therapy (BCT) at William Beaumont Hospital. Each patient had at least an excisional biopsy. Radiation consisted of 45-50 Gy to the entire breast followed by a supplemental boost dose, so that a minimum of 60 Gy was delivered to the tumor bed. Thirty cancers were classified histologically as infiltrating lobular carcinoma (ILC), 346 as infiltrating ductal carcinoma (IDC), and 26 as other. Median follow-up is 60 months. There was no significant difference in 5 year actuarial local recurrence rates between ILC and IDC, 3.3 versus 4.2%, respectively, (P = not significant). Preoperative mammograms were retrospectively reviewed for 29 of the 30 ILC patients. A spiculated opacity was the most common primary mammographic finding (63%), followed by architectural distortion (17%), poorly defined opacity (7%), and negative (7%). Of the patients who had a preoperative primary mammographic finding of a spiculated opacity, 55% underwent reexcision after the initial excisional biopsy, and residual invasive carcinoma was found in 18% of the reexcision specimens. In contrast, of the patients with a primary mammographic finding of an architectural distortion, poorly defined opacity, or negative, 89% underwent reexcision after an initial excisional biopsy, and residual invasive carcinoma was found in 100% of the reexcision specimens. Infiltrating lobular carcinoma does not have a worse local recurrence rate compared with IDC when each is treated with breast-conserving therapy. The primary finding on preoperative mammograms in patients with ILC may prove to be a useful tool for predicting the likelihood of residual carcinoma in the breast after initial excisional biopsy.

Re-excisions of scar in primary cutaneous melanoma: a histopathological study

In many centres the wide excision and split-skin grafting remains the standard therapy for primary cutaneous melanoma. One-hundred and thirty-seven primary cutaneous melanomas were seen in our department during a 3-year period; 25 patients were subsequently subjected to re-excision of scar following the initial excision biopsy. Lymphatic permeation, field change in the epidermal melanocytes and micrometastases were sought in the re-excision specimens in order to examine the pathological basis for this therapy. Two of the 25 primary melanomas included in this study were known to have been incompletely excised at the time of initial biopsy and both re-excision specimens included a few nests of atypical melanocytes adjacent to one edge of the biopsy wound. Examination of the re-excision specimens failed to demonstrate evidence of direct lymphatic permeation by melanoma, or of a field change in the epidermal melanocytes adjacent to the melanomas, although five specimens from sun-exposed sites showed slight melanocyte atypia. One re-excision specimen did include a single small group of melanocytes, less than 120 microns in size, in the dermis within 2 mm of the initial excision biopsy site of a melanoma 8.4 mm in thickness. These results support the view that more extensive local therapy than complete excision of primary cutaneous melanoma with a narrow margin of adjacent normal skin, is unlikely to benefit the patient.

Primary Culture of Cells Arising from a Neuroendocrine Skin Carcinoma

A carcinoma arising in the skin of the lip metastasized to the lymph nodes in the neck of a 53-year-old white man. Electron microscopy of the initial excisional biopsy specimen revealed that the tumor cells contained dense-cored vesicles (100 nm in diameter) in their cytoplasm and were joined by simple junctions. Cells from the nodal metastases were found to be immunoreactive for neuronspecific enolase, keratin intermediate filaments, and chromogranin A, but not for neurofilaments. The tumor was thus classified as a neuroendocrine skin carcinoma. In addition, its metastatic cells shared immunoreactive and ultrastructural characteristics of Merkel cells, which are situated in the basal epidermis of normal skin. Primary cultures from a nodal metastasis were established and characterized. The cells attached and proliferated on culture flask surfaces. The population-doubling time was 2 days. This is the first report where cells from a neuroendocrine skin carcinoma have been demonstrated to retain their characteristic ultrastructure in an in vitro environment (10 days). Studies of cells cultured from neuroendocrine skin carcinomas may prove useful in understanding the pathobiology of this disease and help define the in vitro growth requirements of nontransformed Merkel cells as well.

Results of re-excisional biopsy of the primary tumor in preparation for definitive irradiation of patients with early stage breast cancer.

From December 1977 through November 1984, 251 patients underwent a re-excisional biopsy procedure in preparation for definitive radiation therapy because of uncertainty in the extent of the initial biopsy procedure. Analysis of the cases was limited to patients with AJC Clinical Stages I or II breast cancer and whose initial biopsy procedure demonstrated invasive carcinoma. Sixty-three percent (158/251) of the 251 re-excisions were positive for residual tumor, and 37% (93/251) did not show any residual tumor. Of the positive re-excisions, 85% (134/158) revealed an invasive component of tumor; 15% (24/158) revealed only non-invasive disease. For patients whose initial biopsy was described as incisional only, 97% (64/66) had residual tumor; 51% (94/185) of patients with an initial excisional biopsy had residual tumor. Because of the extremely high rate of positive re-excision in patients with an initial incisional biopsy, these cases were excluded from the remainder of the analysis. When the pathologic margin of the initial biopsy specimen was described as positive, 60% (15/25) had residual tumor on re-excision and 49% (79/160) when the pathology margin was unknown. Of the clinical T1 lesions, 45% (57/126) had positive re-excision, and of the clinical T2 lesions, 63% (37/59) were positive. When a post-biopsy mammogram (i.e. following initial biopsy procedure but before re-excision) showed residual microcalcifications, 86% (12/14) had residual tumor found in the re-excision specimen. Based on these findings, indications for re-excisional biopsy of the primary tumor are: initial incisional biopsy, positive or unknown pathologic margin on an initial excisional biopsy specimen, or residual microcalcifications on post-biopsy mammogram. When inked margins were negative on pathological examination of an initial excisional biopsy specimen, re-excision of the primary tumor bed was not recommended. These results suggest that a re-excisional biopsy procedure may be an important component of the overall treatment approach to assure removal of all tumor, and should continue to be used when indicated prior to definitive irradiation of the breast for early stage breast cancer.

Thin (&lt;1 mm) Melanomas of the Extremities Are Biologically Favorable Lesions Not Influenced by Regression

Although a thickness of less than or equal to 0.76 mm has been used to define biologically favorable (thin) melanoma, there is evidence that 1 mm may be a reasonable cutoff to categorize favorable extremity melanomas. This is tempered, however, by the claim that histologic regression in thin melanomas is associated with an increased metastatic rate. We have therefore addressed the following questions: Is 1 mm an appropriate cutoff point to define thin melanoma on the extremities? Does regression in a thin lesion truly signify a poor prognosis? Is the width of excision (narrow vs. wide) related to recurrence rates in these lesions? To address these issues we reviewed 48 patients with extremity melanomas, less than or equal to 1 mm in maximum thickness, treated at this institution during a 20-year period. Pathologic features included histologic type: superficial spreading (90%), nodular (6%), and not classified (4%); thickness: less than 0.76 mm (61%) and 0.76 to 1 mm (39%); and Clark's level: II (33%), III (63%), and IV (4%). A moderate or marked lymphoid infiltrate occurred in 75%, and histologic tumor regression was found in 50%. The median margin of excision, as stated by the surgeon, was 4 cm. The median margin measured by the pathologist in unfixed specimens was 3.5 cm. Although 13% had atypical melanocytic hyperplasia in the initial excisional biopsy margin, all reexcisions were clear. Of 21 patients having node dissections, none had nodal metastases. There were no recurrences or deaths due to melanoma (median follow-up: 90 months). We conclude that melanomas less than or equal to 1 mm in thickness on the extremities can be defined as biologically highly favorable, "thin" lesions. Foci of regression do not alter their behavior. Their favorable prognosis justifies conservative excision in most cases.

Characteristics of some co-trimoxazole-resistant Enterobacteriaceae from infected patients.

Two isolates of Proteus mirabilis and four of Esch. coli which would not grow on commonly used commercial sensitivity test media are reported. These organisms appear to be resistant to co-trimoxazole, are exacting towards thymidine, and five of six were isolated from patients who had been treated with co-trimoxazole. A method for the detection of these strains is given and their significance in the laboratory and clinical practice discussed.