Touch preparations in the rapid intraoperative diagnosis of central nervous system lesions. A comparison with frozen sections and paraffin-embedded sections

Cytologic preparations provide a rapid, simple method for intraoperative diagnosis of central nervous system (CNS) lesions. Details of cellular morphology are defined sharply, avoiding artifacts often introduced by the frozen section technique. In 100 neurosurgical biopsies performed between 1984 and 1986, touch preparations and cryostat (frozen) sections were made at the time of surgery for preliminary intraoperative diagnosis. To assess the accuracy of each of the diagnostic methods used independently, slides obtained with each of the two techniques were later reviewed retrospectively with appropriate clinical and radiological data, but without knowledge of the final neuropathological diagnoses. When compared with the final diagnoses, intraoperative diagnoses were confirmed in 95 cases. The diagnoses based on cytologic and frozen section techniques were compared with the final diagnoses based on paraffin sections. Touch preparation diagnosis was confirmed by paraffin sections in 76 cases; in 18 additional cases a clinically useful, but nonspecific diagnosis (benign versus malignant, glial versus nonglial) was established by touch preparation. In five cases with firm or rubbery tumors, insufficient cells were imprinted for reliable evaluation, and no definitive diagnoses could be made. Specific cryostat diagnoses were confirmed by paraffin sections in 88 cases; nonspecific diagnoses were made in 11 cases. A single incorrect diagnosis was obtained with each technique. When the two techniques were used together, a specific and accurate diagnosis was achieved in 95 cases. Touch preparations were superior to frozen sections for evaluating soft or highly cellular tumors and for preliminary diagnosis from a minute surgical specimen (i.e., stereotactic biopsy).(ABSTRACT TRUNCATED AT 250 WORDS)     

Schnellschnittdiagnostik bei Erkrankungen des weiblichen Genitaltrakts

Intraoperative frozen sections are particularly important for ovarian tumors because definitive preoperative histology is not possible. The diagnostic accuracy of frozen sections is highest for primary invasive ovarian carcinomas and benign ovarian lesions, followed by borderline tumors and poorest for ovarian metastases and rare neoplasms, such as germ cell tumors. Endometrial carcinoma should be diagnosed preoperatively by curettage or biopsy. For endometrioid endometrial carcinomas the indications for lymphadenectomy are often based on intraoperative assessment of the uterus. The differential diagnosis of low grade stromal neoplasms is based on myometrial invasion and can be supported by assessment of frozen sections as well as the diagnosis of other mesenchymal uterine tumors suspected of being malignant. Frozen sections of pelvic lymph nodes provide the possibility of immediate subsequent para-aortic lymphadenectomy in endometrial and cervical carcinomas but have recently lost importance. Sentinel node biopsy with intraoperative frozen section analysis is routinely performed only for vulval carcinoma. The German Association of Gynecological Oncology (AGO) recommends deferred diagnosis and a two stage surgical procedure for any doubtful intraoperative ovarian histology. Intraoperative frozen sections for endometrial carcinoma and lymphadenectomy specimens as well as for sentinel node biopsies are currently not recommended but are also not completely rejected.     

Intraoperative Schnellschnittdiagnostik des Urogenitaltrakts

Up to now intraoperative frozen section, diagnosis has been of limited utility in urologic oncology. In the future, it may become more important due to a significant increase in the number of nerve-sparing operations performed for prostate cancer. Accuracy and benefit of intraoperative frozen sections depend both on a good communication between surgeons and pathologists as well as on a strict assessment of the need for surgery in the individual patient. In order to optimize cost-efficiency and to reduce the associated risks the indications for intraoperative frozen sections must be rigorously appraised. This report outlines clinically relevant indications for intraoperative frozen section diagnosis in tumors of the urinary tract, kidneys, prostate, testis and penis according to the most recent guidelines. The diagnostic scope and problems of this method are also discussed.     

Current practices in performing frozen sections for thyroid and parathyroid pathology

In this review article, current trends in thyroid and parathyroid frozen sections are discussed. In Japan and other countries, the numbers of thyroid frozen sections have been dramatically decreasing over the past decade. The decline in the number of thyroid frozen sections has been attributed to two major factors: highly diagnostic preoperative fine needle aspiration for papillary carcinomas, the most frequent type of thyroid cancers, and the acknowledgment in the literature of the disadvantageous frozen sections for follicular tumors. Several authors have argued that the frozen section of thyroid nodules should be limited only to cases that have a preoperative cytology diagnosis as "atypical" or "suspicious". In contrast, frozen sections for parathyroid glands have been increasing in numbers. This increase is thought to be largely due to the high number of parathyroidectomies for secondary hyperplasia in dialysis patients. Frozen sections are usually performed to confirm the removal of parathyroid tissue for either cyropreservation or auto-transplantation. It is concluded that thyroid and parathyroid frozen section examination is restricted to selected situations.     

Diagnostic pitfalls of infarcted Warthin tumor in frozen section evaluation

Warthin tumor (WT) is the second most common benign salivary gland neoplasm and has characteristic cytologic and histologic findings. Fine-needle aspiration is a common and useful preoperative diagnostic technique, which sometimes leads to ischemic injury resulting in the infarction of these lesions. Infarcted WT may demonstrate variable gross and histologic alterations that may render the diagnosis challenging, particularly during intraoperative frozen section evaluation.In this study, we collected 11 resection specimens from 9 patients with infarcted WT. Seven patients were men and 2 were women, ranging from 49 to 85 years (mean, 69). All the patients had fine-needle aspiration before the resection. Macroscopically, the tumors were tan-white and contained soft, yellow, exudative material. The histologic findings were variable and included necrosis, ghosts of papillae, squamous metaplasia, cholesterol clefts, foamy macrophages, multinucleated giant cell reaction, necrotizing granulomas, and fibrosis. Each case predominantly demonstrated 1 or 2 of these histomorphologic features. In the permanent sections, additional sampling revealed foci of residual viable WT in 8 cases. Three cases were completely infarcted; however, they all had ghost-like papillae in which the architecture of WT was evident.Infarcted WT may present a diagnostic challenge during intraoperative frozen section evaluation. Associated morphologic alterations may preclude a definitive diagnosis of WT and may mimic malignancy. Awareness of the gross and microscopic features associated with infarcted WT is important, particularly for accurate frozen section evaluation of these salivary gland tumors.     

Der intraoperative Schnellschnitt im Umgang mit Weichteiltumoren

Due to the multiplicity of localizations and entities, handling of soft tissue tumors is a very challenging subject requiring intensive interdisciplinary collaboration. With respect to the use of intraoperative frozen sections, the following facts are of special relevance: 1) the usual criteria for malignancy, such as infiltrative growth and high mitotic rate are only restrictedly applicable to soft tissue tumors. 2) Correct diagnosis of the tumor entity often requires not only the use of immunohistochemistry but also the identification of genetic alterations by the polymerase chain reaction and/or fluorescence in situ hybridization. In many centres, 14G core biopsies taken from different tumor areas represent the preferred method for a diagnostic biopsy. Apart from cryocollection additional frozen section investigations are used especially in case of open biopsies for quality control of the submitted material or in cases of excision biopsies to ascertain a highly probable radiological diagnosis. The use of intraoperative frozen sections to clarify the resection margins is generally undisputed but should definitely be restricted to centres specialized and experienced in the handling of soft tissue tumors.     

Accuracy of frozen section diagnosis in soft tissue tumors

This study was undertaken to analyze the accuracy of frozen section (FS) diagnosis of 118 soft tissue tumors with respect to the reasons for which the intraoperative consultation was indicated. Fifty-seven frozen sections were performed for the diagnosis of an unknown pathologic process. Complete agreement was established in 40.3% and the correct pathologic process in 43.9%, the diagnosis was deferred in 14%, and the remaining 1.8% were diagnosed incorrectly. Examination for determination of the adequacy of resection margin (22 cases), lymph node or skip metastases (23 cases), residual or recurrent tumor after previous surgery (29 cases), viable tumor tissue after previous locoregional or systemic therapy (ten cases), and identification of the specimen (five cases) proved to be 95.5%, 95.7%, 96.6%, 90%, and 100% accurate. Considering the whole series, an erroneous answer to a question posed by a surgeon was given in four cases (two false positive and two false negative), of which two cases were a sampling error made by pathologist. Intraoperative consultation by FS in soft tissue tumors is (a) reliable for general rather than exact diagnosis in defining the previously unknown pathologic process and (b) mandatory in evaluating resection margins and any discrepancies between preoperative cytologic and intraoperative gross impression.     

Application of crush cytology preparation for rapid diagnosis of brain tumors

The crush cytology perform during the surgery for 22 cases with brain tumors at Surugadai Nihon University Hospital, being compared with frozen and permanent histology sections. Crush cytology, which was generally and less damaged by artefacts than frozen sections. Immunocytochemistry used crush cytology were useful tools for differential diagnosis between undifferentiated glioma and carcinoma. Crush cytology were thought to be useful using together with the frozen sections for intraoperative diagnosis.     

髋关节翻修术中冰冻病理切片与99Tcm三相同位素骨扫描共用诊断髋关节假体周围感染

背景：常规血清学、影像学和实验室诊断方法诊断假体周围感染难以达到理想的灵敏度、特异度和准确性。尤其对于假体置换后晚期假体低毒性感染性松动和无菌性松动之间的鉴别诊断还缺乏普遍接受的诊断标准。术前、术中和术后多种诊断方法的联合运用对于明确感染诊断和制定手术翻修策略有重要的临床意义。 目的：通过初次髋关节置换后翻修术前和术中联合运用99Tcm三相同位素骨扫描和冰冻病理切片多形核白细胞计数方法诊断髋关节假体周围感染,并与常规诊断手段相比较。 方法：2008年4月至2013年5月共收治44例髋关节置换后翻修病例,结合临床症状和血清学检查指标,18例患者血沉和C-反应蛋白增高诊断为临床怀疑感染病例组;26例血清学指标正常诊断为临床怀疑无菌性松动病例组。所有患者翻修前进行99Tcm三相同位素骨扫描检查,同时结合翻修手术过程中组织冰冻病理切片结果。如两项结果均为阴性,诊断为假体无菌性松动,行一期翻修手术;反之则诊断为假体周围感染,行二期手术翻修。通过术后临床随访血清学指标及手术疗效,采用受试者工作曲线的统计学方法评估联合运用99Tcm三相同位素骨扫描和组织冰冻病理切片的诊断价值。 结果与结论：18例临床感染病例组中16例患者术前99Tcm三相同位素骨扫描结果和术中冰冻病理结果均为阳性,诊断为感染,二期翻修;2例结果均阴性,排除感染,一期翻修。26例松动病例组中,25例术前99Tcm三相同位素骨扫描结果和术中冰冻病理结果阴性,诊断为无菌性松动,一期翻修;1例患者术后病原菌微生物学培养送检3个标本中1个标本培养出金黄色葡萄球菌,诊断为假体周围感染,仍采取一期翻修。增加99Tcm三相同位素骨扫描和冰冻病理切片多形核白细胞计数的方法后,工作特征曲线面积由0.906上升至0.972,感染诊断灵敏度由89%上升至94%,特异度由92%上升至100%。但诊断方法前后比较差异无显著性意义。提示血清学和影像学检查等常规诊断基础上增加99Tcm三相同位素骨扫描和术中冰冻病理切片技术能够鉴别感染性和无菌性髋关节假体松动。99Tcm三相同位素骨扫描阴性结果同假体无菌性松动的确诊有很高的相关性,具有很好的排除感染的诊断价值,结合术中冰冻病理切片多形核白细胞计数的方法对于翻修手术方式的选择具有积极的临床价值。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程全文链接：     

Touch imprints in the intraoperative diagnosis of anterior mediastinal neoplasms

OBJECTIVE: To evaluate the accuracy of intraoperative diagnosis of mediastinal lesions using touch imprints and frozen sections. DESIGN: We studied touch imprints and frozen sections from 21 anterior mediastinal lesions retrospectively. The lesions included six cases of non-Hodgkin's lymphoma, eight thymomas, two thymic carcinomas, three Hodgkin's disease cases, and two seminomas. Slides were reviewed independently by each of the three authors, and diagnoses were recorded. RESULTS: Depending on the observer, the correct diagnosis was obtained on touch imprints alone in 76% to 81% of cases. On frozen sections alone, the correct diagnosis was made in 67% to 86% of cases. In 86% to 100% of cases, the correct diagnosis was made on either touch imprint or frozen section. CONCLUSIONS: As with frozen sections, the most common significant error in interpreting cytology preparations was in distinguishing thymic epithelial tumors (thymoma and thymic carcinoma) from lymphoma. On a modified Wright-Giemsa-stained imprint, epithelial cells in a thymoma may be inconspicuous. Clues to their presence include cells with a spindled nuclear shape or a small distinct nucleolus. The epithelial cells have scant cytoplasm with indistinct cell borders. Clumping of cells is often not prominent in lymphocytic thymomas, but may be present in epithelial or mixed lymphocytic and epithelial tumors. With practice, one can learn to recognize thymic epithelial cells on touch imprints. Familiarity with this simple inexpensive technique could improve the accuracy of intraoperative diagnosis of anterior mediastinal lesions.     

Intraoperative imprint cytology: its significance as a diagnostic adjunct

We retrospectively evaluated 664 specimens submitted for intraoperative frozen-section analysis for which cytologic imprints or smears were also prepared; 238 (36%) were malignant neoplasms. These preparations were retrospectively evaluated independently by three reviewers of varied experience in the detection of malignancy. The number of false-positive and false-negative results were recorded, and various assessment parameters (sensitivity, specificity, efficiency, and predictive value) were calculated. The imprint was of chief value as an adjunct to the frozen section, particularly in avoiding false-positive and, to a lesser extent, false-negative interpretations. Experience with the use of intraoperative cytology demonstrated the technique to be of value in providing abbreviated preparation time (3-5 min); supportive diagnostic information when frozen section was equivocal; diagnostic information when frozen-section evaluation could not be done (e.g., excessively small sample); contributory information for final diagnosis on difficult cases; and excellent teaching material for cytopathology.     

Cerebellopontine angle lipoma

Cerebellopontine angle lipomas are rare lesions that differ from other intracranial lipomas in that they typically present with slowly progressive focal signs and symptoms identical to those of other tumors of this location, and by their propensity for intimate involvement of the adjacent cranial nerves. The lipomas in this study demonstrated this tendency to splay apart and infiltrate the cranial nerves, with the fatty tissue adjacent to the nerves invariably containing portions of the cranial nerves. Hence, the dissection of the adipose tissue from the nerves led to greater than anticipated postoperative neurologic deficits. Therefore, minimal excision of tumor is recommended to achieve decompression. Since preoperative evaluation does not distinguish with certainty this lesion from others more common to this location, intraoperative examination of frozen sections is required to confirm the diagnosis.     

Schnellschnittdiagnostik in der Osteopathologie

Bone tumors are very rare and this is the reason why frozen section diagnosis is often difficult. The orthopedic surgeon wants to know the intraoperative diagnosis of biopsies of benign or malignant bone tumors so that definitive treatment can be carried out immediately in cases of diagnostic certainty. Diagnostic problems not only concern the distinction of benign and malignant tumors but also differentiation of a neoplastic from a reactive process. Clinical information is very important and all patients with bone tumors are discussed before surgical treatment in an interdisciplinary tumor board. Internationally but with the exception of the USA, the diagnostic procedure using frozen sections is not commonly used even in specialized centers.     

Why do frozen sections have limited value in encapsulated or minimally invasive follicular carcinoma of the thyroid?

The diagnosis of encapsulated or minimally invasive follicular carcinoma of the thyroid requires the proof of vascular or capsular invasion. The aim of the present study was to evaluate the relationship between intraoperative diagnosis (benign, suggestive of carcinoma, or malignant) and the final histopathologic criteria for encapsulated or minimally invasive follicular carcinoma (tumor size, capsular invasion, vascular invasion, and differentiation). This was a retrospective study of 63 cases of encapsulated or minimally invasive carcinomas, with the final histopathologic diagnosis taken as the "gold standard." The sensitivity of frozen sections for the diagnosis of malignant neoplasm was 17%. The median number of vascular invasions was 1, identified with a mean number of 9 paraffin-blocks of the tumor. In most cases, intraoperative frozen sections are unable to establish the proof of malignant neoplasm. Intraoperative study of tumor differentiation is useful to select follicular tumors that require a rapid definitive diagnosis and a completion thyroidectomy within 48 to 72 hours (73% of the cases in our study).     

Dipeptidyl(amino)peptidase IV in the differential diagnosis of thyroid gland tumors: methods and results of a pilot study of 200 cases

The use of dipeptidyl aminopeptidase IV (DPP IV) staining by azo-coupling in preoperative and intraoperative diagnostics of thyroid lesions is presented. In a series of 200 histologically confirmed cases examined, the sensitivity and the specificity were 71% and 99%, respectively in 124 smears, and 70% and 94%, respectively in 189 frozen sections. DPP IV expression showed high negative predictive value as well. DPP IV is suggested as an additional tool in the preoperative and intraoperative diagnostics of thyroid lesions.     

Use and abuse of frozen section in the diagnosis of follicular thyroid lesions

The role of intraoperative frozen section in certain organ systems such as the thyroid continues to be problematic. In many cases, diagnoses are deferred or nonhelpful—“follicular lesion.” In the modern era, the widespread use of preoperative aspiration biopsy has allowed for more careful selection of patients who undergo thyroid surgery. In many cases, the fine-needle-aspiration (FNA) biopsy diagnosis can be definitive or can guide the specific surgical procedure. The literature supports our approach, which is summarized as follows: Intraoperative consultation is not needed on the intrathyroidal nodule if a preoperative FNA was definitive for papillary carcinoma. Frozen section is of no value in the intraoperative diagnosis of lesions diagnosed on FNA as “follicular neoplasm” or “Hürthle cell neoplasm” because the characterization of these lesions requires detailed analysis of the tumor capsule for the demonstration of capsular and/or vascular invasion—an analysis that is not practical in the intraoperative setting. Finally, intraoperative consultation including frozen section and intraoperative cytologic examination is most useful in those cases that are diagnosed as suspicious for papillary carcinoma by FNA, because the assessment of nuclear features needed for the definitive diagnosis is possible with intraoperative techniques in a significant number of cases.     

Utility of intraoperative consultation touch preparations

Although intraoperative touch preparations (TPs) often are performed in conjunction with frozen sections, the comfort level of using TPs in actual practice and the effect of TP quality and cytologic experience on diagnostic accuracy have not been measured. To investigate the utility of intraoperative TPs and to compare them with that of frozen sections, five pathologists of differing levels of cytologic experience retrospectively reviewed 122 intraoperative TPs and frozen sections. Accuracy rates for individual pathologists were calculated and the accuracy using TPs was compared to that of frozen sections. TP accuracy was correlated with TP quality and cytologic experience. The mean rates of correct, incorrect, and atypical TP diagnoses were 88.5%, 4.1%, and 7.4%, respectively. The mean rates of correct, incorrect, and deferred frozen section diagnoses were 86.1%, 2.5%, and 11.9%, respectively. For the four pathologists with cytologic experience, both TP and frozen section diagnostic accuracy rates were similar; however, the pathologist who lacked cytologic experience had lower TP diagnostic accuracy. All pathologists who had cytologic experience requested a frozen section for cases with an atypical or incorrect TP diagnosis. In cases with a correct TP diagnosis a frozen section was requested 46.3% of the time. TPs of greater technical quality were associated with higher diagnostic accuracy. In conclusion, the use of performing TP and frozen section are complementary and result in increased diagnostic accuracy. For some pathologists, TPs may replace frozen sections in over 50% of cases.     

Intraoperativer Gefrierschnitt der Schilddrüse

The goal of evaluation of intraoperative frozen sections of the thyroid gland is to achieve a definitive diagnosis which determines the subsequent surgical management as fast as possible; however, due to the specific methodological situation of thyroid frozen sections evaluation a conclusive diagnosis can be made in only some of the cases. If no conclusive histological diagnosis is possible during the operation, subsequent privileged processing of the specimen allows a final diagnosis at the latest within 48 h in almost all remaining cases. Applying this strategy, both pathologists and surgeons require a high level of communication and knowledge regarding the specific diagnostic and therapeutic peculiarities of thyroid malignancies because different surgical strategies must be employed depending on the histological tumor subtype.     

Preoperative and intraoperative diagnosis of low-grade adenosquamous carcinoma of the breast: potential diagnostic pitfalls

AIMS: Low-grade adenosquamous carcinoma (LGAC), a rare variant of metaplastic breast cancer, may mimic benign or other low-grade malignant lesions histologically. Diagnostic difficulty may be encountered when evaluating breast cytology, core needle biopsy or intraoperative frozen section specimens. METHODS AND RESULTS: Pathology reports, cytology aspirates and histological slides of LGAC diagnosed at the Department of Pathology, Singapore General Hospital, were reviewed. Four cases of LGAC were analysed. Cytology from the first case showed atypical cells and the subsequent surgical excision specimen showed a complex sclerosing lesion with LGAC. The second and third cases were investigated by core needle biopsies: the preoperative histological features were suggestive of but not diagnostic of LGAC, until further excision biopsies were performed. The fourth case entailed a frozen section specimen, for which definitive diagnosis was deferred to paraffins. The patients remained well with no evidence of recurrent disease to date. CONCLUSIONS: When limited material, in the form of needle aspirates, core biopsy specimens or frozen sections, is submitted for histology, making a diagnosis of LGAC is not only challenging, but may be impossible. In difficult cases, careful pathological assessment, clinicopathological correlation and follow-up or complete excision biopsy may prove invaluable in establishing a definitive diagnosis.     

Solitary pulmonary capillary hemangioma: Clinicopathologic and radiologic characteristics of nine surgically resected cases

Background

Solitary pulmonary capillary hemangioma (SPCH) is an extraordinarily rare capillary derived mesenchymal neoplasm. Although routine morphology and immunohistochemistry are adequate for the diagnosis of classical SPCH in surgical specimens, true gross appearance identification of most tumor themselves and diagnosis for some exceptional cases are still very difficult. Furthermore, preoperative imaging and frozen diagnosis remain a challenge.