The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.
Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29–202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.
Cervical cone biopsy has become an important surgical procedure for endocervical adenocarcinoma in situ (AIS), especially for patients who desire to retain their fertility. Establishing the usefulness of the endocervical margin status in cone biopsy specimens as a predictor of residual AIS is paramount. We examined the status of the endocervical margin in the cone biopsy specimen, the distance between the most proximal AIS and the endocervical margin in the cone biopsy specimen, and the endocervical curettage (ECC) specimen performed at the time of cone biopsy and residual AIS in the hysterectomy specimens of 61 patients with specimens accessioned from 1968 through 1997; 43 (30%) of patients with a negative endocervical margin had residual AIS in the hysterectomy specimen. Conversely, 10 of 18 (56%) patients with a positive endocervical margin in the cone biopsy specimen had no AIS in the hysterectomy specimen. All 6 patients with AIS in the ECC specimen had residual AIS. No patient with an endocervical margin in the cone biopsy specimen greater than 10 mm had residual AIS. Patients with distances less than 10 mm had equal percentages of residual AIS. In general, more patients with a negative endocervical margin in the cone biopsy specimen had no residual AIS in the hysterectomy specimen than those with a positive endocervical margin in the cone biopsy specimen. However, the status of this margin is not useful for predicting the presence of residual AIS. Pathologists should report the distance between the endocervical cone biopsy margin and the closest AIS.
Trends in surgical practice suggest that pathologists will encounter increased numbers of patients with small invasive ductal adenocarcinomas; small, if any, metastatic deposits in axillary lymph nodes (ALNs); and possibly fewer ALN specimens to examine. New prognostic histologic features may be needed in this environment. We studied histologic features of primary breast carcinoma and ALN metastasis from 86 patients who had stage T1 ductal carcinomas with only 1 ALN metastasis that was 0.5 cm or less and correlated these features with the development of distant metastases to evaluate their potential usefulness as prognostic indicators. The median follow-up period was 5.3 years. Distant metastases developed in 12 patients. Features significantly associated with 10-year distant metastases–free survival were lymph node hilar tissue invasion (HTI) and ALN metastasis size (stage N1a vs N1b). Tumor grade 1 vs grades 2 or 3 approached significance. The presence of HTI also was related significantly to a decreased 10-year distant metastases–free survival in the stage Nib group. Our study suggests that HTI, along with other well-known parameters, is a useful prognostic feature. In addition, it supports the opinion that ALN dissection may provide limited additional information for patients with grade 1, stage Tla, invasive ductal carcinomas. Additional studies are needed to confirm our findings.
The clinical outcome and optimum classification of patients who have sigmoid resection specimens that show the histologic features of Crohn's disease (CD) and diverticulitis is not well defined. Historically, these patients were considered to have coexistent diseases, but recent studies have suggested that the CD-like changes are part of the inflammatory reaction of the diverticulitis. Sorting out these issues has been complicated by the lack of distinction between patients with and without CD in other regions of the bowel, short clinical follow-up periods, and small numbers of patients. We report on the clinical outcome and histology of 29 patients who had sigmoid resection specimens with diverticulitis and CD-like changes. Of the 25 patients who had no prior or concurrent CD at the time of surgery, 23 remained free of CD during the follow-up period (median, 6.0 yrs) and two developed CD in other regions of the bowel. All four patients with CD prior to their sigmoid resection continued to have active CD postoperatively. There were no histologic features of the sigmoid resection specimens that could be associated with the outcome of the patient. These results suggest that CD-like changes within the sigmoid resection specimen are an idiosyncratic inflammatory response to the diverticulosis rather than coexistent CD in the overwhelming majority of patients who do not have prior or concurrent CD at the time of sigmoid resection. Pathologists should be wary about making the diagnosis of sigmoid CD in the context of diverticulitis unless there is CD in other parts of the bowel.
To identify the minimum time necessary for consistent immunohistochemical estrogen receptor (ER) results in our laboratory, we evaluated results in timed fixation blocks and cases with disparate and similar needle core biopsy and partial mastectomy specimens. Tissue sections of 24 ER-positive, invasive breast carcinomas were fixed for 3, 6, 8, and 12 hours and 1, 2, and 7 days. ER values were quantified using the Q score (0–7). In timed fixation blocks, the mean Q score per block was 2.46 for blocks fixed for 3 hours, 5.75 for blocks fixed for 6 hours, and 6.70 for blocks fixed for 8 hours (P < .001). The difference between the case maximum and mean block Q scores was a plateau of almost 0 at 6 to 8 hours of formalin fixation. For needle core biopsy specimen fixation times, the means for specimens with ER-disparate and ER-similar results were 1.2 and 6.3 hours, respectively (P = .01). The minimum formalin fixation time for reliable immunohistochemical ER results is 6 to 8 hours in our laboratory, regardless of the type or size of specimen.
There are few prognostic factors for patients with T1 N0 M0 pulmonary conventional and bronchioloalveolar adenocarcinomas (BACs), despite a 25% to 35% failure rate. To identify prognostic factors related to disease-free survival, we retrospectively studied the histologic features of 218 cases of T1 NO MO adenocarcinomas. The mean overall follow-up was 5.9 years, and the 5-year disease-free survival was 72%; 148 patients (67.9%) were disease-free, and in 57 (26.1%), nonpulmonary metastases developed. Features significantly associated with decreased 5-year disease-free survival were larger tumor size, increasing central fibrosis, most common and highest nuclear grade, lymphatic vascular space invasion, and more than 50% tumor necrosis. Patients with lymphatic vascular space invasion had a 35% 5-year metastases-free survival. A tumor size of 2 to 3 cm, lymphatic vascular space invasion, highest nuclear grade 3, and increased central fibrosis were associated with metastases. Lymphatic vascular space invasion had the strongest odds ratio of 5.4. These histologic features can stratify patients with T1 N0 M0 neoplasms who have an increased risk of metastases. Future studies are needed to address the usefulness of adjuvant therapy for patients with neoplasms that display these negative factors.
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