Intraoperative Pathologic Evaluation Research Articles

Is there any utility to frozen section or immunohistochemistry examination of the sentinel lymph node (SLN) in patients with ductal carcinoma in situ (DCIS)?

1091 Background: Whether SLN biopsy (SLNB) should be performed in patients with DCIS is controversial. Many centers perform SLNB in DCIS believing it obviates the need for re-operation for axillary staging when invasive cancer (IC) is discovered. Given the low incidence of occult IC detected, whether intra-operative pathologic evaluation during SLNB in DCIS patients provides value has not been addressed. Methods: Demographic and clinico-pathologic data was collected and analyzed for all patients undergoing surgical resection for DCIS between 2004-2010 in order to determine the sensitivity, specificity and accuracy of frozen section (FS) and immuno-histochemistry (IHC) examination of the SLN, and its’ impact on axillary management. Results: 267 DCIS patients (median age 57 years) underwent lumpectomy (N=72) or mastectomy (N=195) with SLNB, intra-operative FS and IHC evaluation. Pre-operative pathology was DCIS (N=231), DCIS with micro-invasion (< 2 mm, N= 24) and DCIS associated with other lesions (N=12). SLN metastasis (SLNM) was identified in 13 patients (4%), of which only 4 were FS positive (1%). SLN micrometastasis (≤ 2 mm) and individual tumor cells (ITCs) were detected by IHC in 10 of 13 patients, while 3 patients had macro-metastasis. Overall, 50 patients (19%) had IC on final pathology. The FS was falsely negative in 9 patients (7%), and had sensitivity, specificity and accuracy of 31%, 100% and 98% respectively in identifying SLNM. 8 of 13 patients with SLNM underwent axillary lymph node dissection (ALND) of which only 1 patient (with macro-metastasis) had further axillary metastasis. On a need to treat basis, 30 and 91 patients would have to undergo FS and IHC exam respectively to identify 1 patient with a metastasis. Conclusions: SLN metastasis in DCIS is uncommon and the prognostic significance of micro-metastasis or ITCs in DCIS is unknown. Given the infrequent higher axillary nodal involvement and low sensitivity and yield of FS and IHC evaluation in DCIS particularly for identifying candidates for ALND, these procedures can be safely omitted thereby reducing operative time and cost. Additional studies are needed to validate these results.

Correlation of macroscopic and microscopic pathology in risk reducing salpingo-oophorectomy: Implications for intraoperative specimen evaluation

Objective A minority of risk-reducing salpingo-oophorectomy (RRSO) specimens from BRCA mutation carriers will contain clinically occult carcinoma that is detectable only using a specialized pathologic evaluation protocol. Although intraoperative detection of cancer may alter immediate surgical management, technical complications impairing pathologic diagnosis may result if fresh tissue dissection and frozen sections are performed on unselected RRSO specimens. We hypothesize that macroscopic specimen findings may predict which RRSO specimens contain cancer and therefore may guide selection of specimens for intraoperative pathologic evaluation. The aim of this study was to correlate the macroscopic and microscopic pathologic findings in RRSO. Methods RRSO specimens from 134 women with a BRCA mutation were retrospectively classified by their grossly visible findings (cysts and/or nodules versus grossly unremarkable). Correlation of the gross findings with the microscopic finding of occult tubal and/or ovarian carcinoma was performed by re-examination of all pathology slides. Results While 46% of RRSO had visible ovarian cysts and 34% had visible tubal/paratubal cysts, no cyst contained cancer on microscopic examination. Carcinoma was detected in 2/22 (9%) visible ovarian nodules and in 2/8 (25%) visible tubal nodules. Conversely, among all 11 RRSO specimens containing cancer, 7 (64%) had no corresponding visible abnormality. Conclusion Frozen section evaluation of a solid nodule may be valuable in patients consented for immediate surgical staging. Otherwise it is best to avoid intraoperative dissection or frozen section of RRSO that are macroscopically normal or contain only cysts; such specimens should remain undissected for immediate formalin-fixation as the first step of the specialized pathology evaluation protocol.

Pathology Issues Related to SN Procedures and Increased Detection of Micrometastases and Isolated Tumor Cells

The goal for the pathologist when dealing with sentinel nodes (SNs) of breast cancer patients is not to find all metastases, but to find clinically relevant metastases: those associated with further metastases beyond the SN, necessitating further locoregional treatment, or indicating an adverse prognosis, necessitating adjuvant systemic therapy. Pathology examination of the SN has to be done more with more attention than usual and can be done pre-operatively, post-operatively, but also intra-operatively to allow immediate axillary lymph node dissection when necessary. There are several means for pre-operative, intra-operative and post-operative SN pathological evaluation. These include fine needle aspiration cytology, gross examination, imprint cytology, frozen section analysis, histopathological investigation by step sectioning, immunohistochemistry, and molecular analysis. In this paper, we provide an up to date discussion on the virtues and flaws of these different methods to find SN metastases, and provide recommendations on the optimal pathology protocol for breast cancer SNs.

Advantages of partial intraoperative pathologic evaluation of sentinel lymph node biopsy – our experience in 267 cases of breast cancer and review of the methods

Aims: Sentinel lymph node biopsy has replaced the axillary lymph node dissection (ALND) in primary surgery for breast cancer in many hospitals and is expected to become the standard of care in due time. Since the sentinel lymph node is subjected to more extensive pathologic examination than the lymph nodes in the axillary dissection specimen, more patients are found to be node positive (N+); however many of them contain micro-metastases (≤2 mm). The consequence may be an overshoot of therapy: additional surgery for non-metastatic lymph nodes or systemic adjuvant therapy.Methods:We examined 34 (out of a series of 38) clinically T1 (cT1) patients who had a SLN biopsy with or without ALND and compared them to a matched historical control group.Results: Twenty-one of 34 (62%) patients showed tumour cells in their SLN's. From these 21 patients in 13 (62%) the SLNs contained isolated tumour cells, of which 10 (77%) were detected only by immunohistochemistry (IHC), in four (19%) the SLNs contained micrometastases, and in four (19%) macrometastases. From 16 patients with isolated tumour cells or micrometastases in the SLN who underwent a regular ALND one had an H&E detected isolated tumour cell in a non-SLN and one patient with isolated tumour cells in the SLN who did not get a regular ALND developed an axillary recurrence 11 months after the primary treatment. On the other hand, three of four (75%) patients with macrometastases in the SLN had pathologically involved non-SLNs. In the majority (70%) of patients of the historical control group no lymph node involvement was seen. The percentage of macrometastases staged as lymph node positive in the control group was the same as in the studied group.Conclusion: Most patients with cT1 breast cancer with isolated tumour cells or micrometastases in the SLN will not benefit from additional axillary dissection; 88% had a negative ALND. Since we cannot select the group that will benefit from ALND, this is still indicated in case of isolated tumour cells or micrometastases in the SLN. Since most of the affected SLNs show isolated tumour cells and are classified as pN0(i+), stage migration due to more meticulous pathologic examination does not occur according to the TNM classification. However some patients do not benefit from the introduction of the SLN, due to the high incidence of isolated tumour cells or micrometastases in the SLN. Many more patients than expected still end up with an ALND.

European Trends in Preoperative and Intraoperative Nodal Staging: ESTS Guidelines

Preoperative and intraoperative lymph node (LN) staging is of paramount importance for patients with non-small cell lung cancer. The Council of the European Society of Thoracic Surgery took the initiative to organize workshops on intraoperative and preoperative mediastinal LN staging. This resulted in specific guidelines. Relevant peer-reviewed publications on these subjects, the experience of the participants, and the opinion of the European Society of Thoracic Surgery members contributing online were used to reach a consensus. For primary staging, mediastinoscopy remains the gold standard for the superior mediastinal LNs. Invasive procedures can be omitted in patients with peripheral tumors and negative mediastinal and hilar nodes on positron emission tomography scan. Positron emission tomography-positive mediastinal findings should always be cytohistologically confirmed. New minimally invasive techniques that provide cytohistological diagnosis became available. Their specificity is high, but the negative predictive value is low. If they yield negative results, an invasive surgical technique remains indicated. For restaging, invasive techniques providing cytohistological information are advisable. Systematic nodal dissection is recommended in all cases to ensure complete resection. Lobe-specific systematic nodal dissection is acceptable for peripheral squamous T1 tumors if hilar and interlobar nodes are negative on frozen section studies. The report from the pathologist should describe the number of LNs removed and studied, the overall number of metastatic LNs in each station, and the status of the LN capsule. We hope that the adherence to these guidelines will standardize and improve preoperative and intraoperative LN staging and pathologic evaluation of non-small cell lung cancer.

Controversies concerning diagnostic guidelines for anomalies of the enteric nervous system: A report from the fourth International Symposium on Hirschsprung's disease and related neurocristopathies

Intestinal Dysganglionoses (IDs) represent a heterogeneous group of Enteric Nervous System anomalies including Hirschsprung's disease (HD), Intestinal Neuronal Dysplasia (IND), Internal Anal Sphincter Neurogenic Achalasia (IASNA) and Hypoganglionosis. At present HD is the only recognised clinico-pathological entity, whereas the others are not yet worldwide accepted and diagnosed. This report describes the areas of agreement and disagreement regarding definition, diagnosis, and management of IDs as discussed at the workshop of the fourth International Meeting on “Hirschsprung's disease and related neurochristopathies.” The gold standards in the preoperative diagnosis of IDs are described, enlighting the importance of rectal suction biopsy in the diagnostic workup. The most important diagnostic features of HD are the combination of hypertrophic nerve trunks and aganglionosis in adequate specimens. Acetylcholinesterase staining is the best diagnostic technique to demonstrate hypertrophic nerve trunks in lamina propia mucosae, but many pathologist from different centers still use H&E staining effectively. Moreover, the importance of an adequate intraoperative pathological evaluation of the extent of IDs to avoid postoperative complications is stressed. Although it is not clear whether IND is a separate entity or some sort of secondary acquired condition, it is concluded that both IND and IASNA do exist. Other interesting conclusions are provided as well as detailed results of the discussion. Further investigation is needed to resolve the many controversies concerning IDs. The fourth International Conference in Sestri Levante stimulated discussion regarding these entities and led to the International guidelines to serve the best interest of our patients.

Primary Tumor Characteristics Predict Sentinel Lymph Node Macrometastasis in Breast Cancer

Selective sentinel lymphadenectomy (SSL) is rapidly becoming the standard of care in the surgical management of patients with early breast cancer. Sentinel lymph node macrometastasis has been well documented in the literature to have a higher risk of nonsentinel node tumor involvement when compared to micrometastasis. The aim of our study was to determine the primary tumor characteristics associated with sentinel node macrometastasis that will allow us to preoperatively determine this subgroup of patients at risk. This study was a retrospective review of 644 patients who underwent successful SSL as part of their surgical treatment of breast cancer at the University of California San Francisco Carol Franc Buck Breast Care Center from November 1997 to August 2003. All patients underwent preoperative lymphoscintigraphy followed by wide excision or mastectomy and sentinel lymphadenectomy with or without axillary lymph node dissection. One hundred twenty-two patients had positive sentinel nodes on histology. Micrometastasis was present in 43 of these patients and macrometastasis in the remaining 79. Statistical analysis showed that a tumor size greater than 15 mm, poor tubule formation by the tumor cells, and lymphovascular invasion were significantly associated with sentinel node macrometastasis. A high mitotic count showed a trend but was not significant in our study. Patients with a tumor size greater than 15 mm, poor tubule formation, and lymphovascular invasion are at risk of having sentinel node macrometastasis. These patients can be identified preoperatively based on imaging and biopsy criteria, allowing the option of selective intraoperative pathologic evaluation of the sentinel node and immediate completion axillary dissection as necessary.

Noninvasive thymoma in the middle mediastinum

We present a rare case of thymoma that developed entirely in the middle mediastinum. A 60-year-old woman was referred to our hospital with a mediastinal mass. The mass was located in the visceral compartment of Shields' mediastinal classification. Intraoperative pathologic evaluation revealed a thymoma, whereupon total thymectomy was performed. The postoperative course was uncomplicated and the patient received no postoperative adjuvant radiotherapy.

The Use of Frozen Section and Immunohistochemistry for Sentinel Lymph Node Biopsy in Breast Cancer

Intraoperative pathologic evaluation of the sentinel lymph node (SLN) may guide immediate (synchronous) completion axillary lymph node dissection (ALND) for up to two-thirds of patients with nodal disease for breast cancer. The false-negative rates average one-third of cases, and one must be aware of false-positive results as this would result in unnecessary and morbid completion ALND. Currently, the use of immunohistochemistry (IHC) is controversial. There is no question that cytokeratin staining improves the sensitivity; however, there is no evidence that any of these "positive" cells are clinically significant and warrant therapy. Prospective randomized trials will be necessary to confirm or debunk the hypothesis that "sub-micrometastatic" disease has clinical significance.

Frozen section evaluation of cervical cold knife cone specimens is accurate in the diagnosis of microinvasive squamous cell carcinoma

Objectives The purpose of this study was to determine the accuracy of frozen section evaluation of cervical cold knife cone (CKC) specimens in the diagnosis of microinvasive squamous cell carcinoma (SCC). Methods Using ICD-9 codes for invasive and microinvasive carcinoma of the cervix, a medical record from 1986 to 1998 identified 110 potential study subjects. Society of Gynecologic Oncologists criteria including depth of invasion ≤3 mm and absence of lymph-vascular space involvement were utilized for the diagnosis of microinvasion. Twenty-seven patients met study criteria including a frozen section diagnosis of microinvasive SCC on a cervical CKC specimen at our institution. A pathologist, blinded to patient diagnosis, reevaluated the histologic findings, including grade, depth of invasion, and cell type. Results Median age of diagnosis was 41 years. Median follow up was 3.6 years. The median time for pathologic review was 28 min (range 15–44 min). Independent retrospective pathologic review of the permanent sections confirmed the diagnosis of microinvasion in 100% (27/27) of patients. No patient experienced a cervical SCC recurrence. At 10 years, disease-specific survival is 100%. Conclusions Frozen section is reliable in the evaluation of CKC specimens with microinvasive SCC: this may afford a simplified surgical approach in certain cases. This accuracy should not be assumed to apply to adeno- or adenosquamous carcinoma of the cervix. At our institution which relies heavily on intraoperative pathologic evaluation, utilizing frozen section diagnosis as the basis for definitive surgical approach did not negatively impact disease-free survival.

Intraoperative Pathologic Evaluation of a Breast Cancer Sentinel Lymph Node Biopsy as a Determinant for Synchronous Axillary Lymph Node Dissection

Intraoperative Pathologic Evaluation of a Breast Cancer Sentinel Lymph Node Biopsy as a Determinant for Synchronous Axillary Lymph Node Dissection

The Sentinel Node Procedure with Patent Blue V Dye in the Surgical Treatment of Papillary Thyroid Carcinoma

How far to extend the surgical treatment of papillary thyroid carcinoma (PTC) is still an open question. A contribution may come from intra-operative lymphatic mapping because, in other malignancies, the procedure has become an important aid in defining lymph node status. To assess the feasibility of using the sentinel lymph node (SLN) technique with the intratumoral injection of Patent Blue V dye to guide nodal dissection in PTC, 29 patients with a preoperative diagnosis of PTC and no clinical or ultrasonographic evidence of nodal involvement underwent cervicotomy and exposure of the thyroid gland, followed by Patent Blue V dye injection into the thyroid nodule. Total thyroidectomy was subsequently performed, resecting the lymph nodes at levels III, IV, VI and VII. The thyroid, SLN and the other lymph nodes were snap-frozen and submitted for both intra-operative and subsequent definitive pathological evaluation. Intra-operative lymphatic mapping located the SLN in 22/29 patients (75.9%) and the SLN revealed neoplastic involvement in 4/22 (18.2%); other lymph nodes were also positive in 2 cases. In the 18 patients whose SLNs were not metastatic, the other nodes were also disease-free. The SLN technique thus seems helpful in avoiding unnecessary lymph node dissection in PTC without spread to the SLN.

Preoperative evaluation and staging of endometrial cancer

Preoperative examination of a patient for whom a diagnosis of endometrial cancer has been made by office biopsy or dilatation and curettage includes careful history taking and physical examination, with emphasis on the pelvic examination, blood tests, and imaging evaluations of the pelvis, abdomen and chest, and other specific studies related to medical operability. The primary approach to endometrial cancer is surgery, which has been used for staging and treatment since the adoption of the Federation of Obstetrics and Gynecology system in 1988. Pilot studies and the Gynecologic Oncology Group have researched this system extensively and have emphasized the findings that could be defined only by pathologic study of the uterus, adnexa, retroperitoneal lymph nodes, and peritoneal cytologic findings. Preoperative endocervical evaluation is no longer necessary unless gross invasion of the cervix is suspected. However, initial histologic findings can identify patients at high risk, that is, those with high grade adenocarcinomas, clear cell carcinomas, adenosquamous carcinomas, and papillary serous adenocarcinomas. Intraoperative pathologic evaluation of the uterus by frozen section, which reveals depth of invasion into the myometrium and correlation with tumor grade, can identify patients for whom lymph node sampling should be performed.

Tumoral Calcium Pyrophosphate Dihydrate Deposition Disease Mimicking a Cervical Spine Neoplasm

A CASE OF tumoral calcium pyrophosphate dihydrate crystal deposition disease involving the upper cervical spine is reported. It presented clinically, radiographically, and by preliminary intraoperative pathological evaluation as a possible malignant soft tissue tumor. An aggressive resection of the lesion was performed. This case differs from previous reports of calcium pyrophosphate dihydrate crystal deposition disease of the cervical spine by the size, location, and radiographic appearance of the lesion. We suggest that radical surgical procedures should not be performed without consideration of this diagnosis in lesions with similar presentations. A brief review of spinal and tumoral calcium pyrophosphate dihydrate crystal deposition is presented.

The management of high grade dysplasia and early cancer in Barrett's esophagus

The incidence of Barrett's-associated esophageal adenocarcinoma is rising, but experience in the treatment of high-grade dysplasia (HGD) or early cancer is limited. Based on an endoscopic surveillance program, the authors developed a systematic multidisciplinary approach to this problem. Surgical resection was considered if biopsies of the Barrett's segment, performed according to a published protocol, showed invasive cancer, intramucosal carcinoma, or repeated evidence of HGD. The type of resection was based on the length of the Barrett's segment and included an en bloc lymph node dissection for staging purposes. Careful intraoperative pathologic evaluation ensured that all of the Barrett's mucosa was resected. From 1984 to 1993, 27 consecutive patients (23 men, 4 women), with median age of 61 years (range, 45-75 years) underwent surgical exploration. Indications for operation were invasive cancer in 17 patients, intramucosal carcinoma in 5 patients, and HGD in 5 patients. Median length of the Barrett's segment was 9 cm (range, 1-17 cm). Only 15 patients (55%) had abnormalities visible with endoscopic examination that were potentially suspicious for malignancy. Twenty-six patients underwent resection with complete removal of the Barrett's mucosa, 20 by Ivor Lewis esophagogastrectomy, and 6 by transhiatal esophagectomy. Pathologic tumor stages were: TisN0M0 in 10 patients; T1N0M0 in 11 patients; T2N0M0 in 2 patients; T3N0M0 in 3 patients; and T1NXM1 in 1 patient. There were no postoperative deaths or anastomotic leaks. Major complications occurred in 4 patients. With a median follow-up of 3.7 years, 22 patients were alive, and only 2 patients had recurrences. This increasingly important group of patients with HGD or early carcinoma in the Barrett's esophagus has a high chance of cure but requires careful multidisciplinary treatment by the surgeon, gastroenterologist, and pathologist.

Intraoperative imprint cytology for evaluation of mediastinal lymphadenopathy

Frozen-section (FS) analysis of mediastinal lymph nodes is commonly used in the staging of lung cancer and the evaluation of diagnostic tissue at mediastinoscopy. This approach facilitates definitive surgical intervention in a single operation and reduces costs. However, FS analysis can be labor intensive for the pathology department and time-consuming while the patient is anesthetized. Imprint cytology is more rapid than the FS procedure (average, 2 minutes versus 11 minutes per node) and allows more extensive sampling of the specimen. In this prospective study, we compared the diagnostic accuracy of imprint cytology and permanent sections on 121 mediastinal lymph nodes from 38 patients. There were no false-positive results and one false-negative result, although that patient was correctly classified based on positive cytology from another node. The sensitivity was 96.6%, the specificity was 100%, and the predictive value of a positive result was 100%, as no false-positives results were observed. The predictive value of a negative result was 98.9%, and the overall efficiency was 99.2%. These results compare favorably with those in other studies comparing the diagnostic accuracy of imprint cytology with that of FS analysis and with reported accuracy rates of FS technique. Our findings confirm the usefulness of this technique as an adjunct or substitute for FS analysis in the intraoperative pathologic evaluation of mediastinal lymphadenopathy.