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Intraoperative Histological Examination Today
Beitr. Path. Bd. 149,103 -
lIO
(1973)
Review
Department of Clinical Pathology (Chief: Prof. Dr. P. HERMANEK), Surgical Clinic of the University of Erlangen-Nlirnberg (Chairman: Prof. Dr. G. HEGEMANN)
Intraoperative Histological Examination Today Intraoperative histologische Untersuchung heute P.
HERMANEK
With
2
Figures and
I
Table' Received January 3, 1973
In the beginning of our century, the immediate histological examination during surgery became a method of daily practice in several American hospitals. The principle has remained unchanged up to now: the activity of the surgeon must be based upon precise histopathologic information, because the macroscopic findings are often deceptive. Two reasons have induced us to deal once more with the problems of immediate histological examination for diagnostic purposes: (a) The important methodological improvements due to the introduction of the cryostat microtome into intraoperative diagnosis in 1957, and other complementary special methods are far from being generally used. (b) Owing to the constant improvement of surgical methods, the surgeon becomes more and more dependent on the cooperation with the pathologist. I.
The modern standard method
The introduction of the cryostat microtome has been the greatest methodological progress in the intraoperative histological examination. With this apparatus even a less skilled laboratory assistant can produce, within a few minutes, good sections of 6 or 8 [Lm, of native tissue (Fig. I). With the exception of calcified material, tissues of all kind can be properly sectioned by this method. If the cryostat microtome is used for sectioning purposes, the abrupt prefixation often carried out in former times (hot formol) can be abandoned. 8
Beitr. Path. Bd. 149
4 . P. HERMANEK
10
Fig. I. Carcinoma of the breast. Native tissue, cryostat microtome, polychrome methylene blue, non-permanent preparation. X 200.
Consequently, an exact cytological interpretation can be realized at high power magnification. In other words, the immediate freezing does not destroy the tissues to such an extent that later examination of the material embedded in paraffin does no more allow to make an exact diagnosis. LYNN and co-workers have shown that a modern frozen section examination can well be followed by an examination of the same tissue with the electron microscope. The question of the staining of specimens taken intraoperatively has not yet been settled. In the majority of the cases, a quick staining with polychrome methylene blue or other thiazine stains will be sufficient (Fig. I). Many authors and we, too, prefer this method for its rapidity. However, the pathologist who interprets the slides must be familiar with this sort of staining, that means that he must have seen it in many occasions. If an immediate intraoperative diagnosis is required, the shortest staining method must be chosen, that means a fast but unstable one. Time can be saved by short rinsing and covering with a 5 % glucose solution after staining (Fig. 2). Immediately after having made the diagnosis, another successive section can be performed and be treated in such a way that a permanent stain is obtained (fixation of the section, dehydration, inclusion in an anhydrous medium). This slide is used as a proof. As a rule, the materials examined intraoperatively must be embedded in paraffin. We proceed this way even in those cases in which the diagnosis is completely clear. This procedure enables us to make further sections at any moment, and to investigate the material at a later moment in order to clarify scientific problems.
Intraoperative Histological Examination Today· 10 5
bI
I-Itltl-U thiazins
section 1
~-- I CJ I
hematoxylin·eosin
secti,on 2
I
diagnOSIs
not permanent
cryostat mICrotome \
fr~zen s.ec1ion
CJ
7-tl tjtltl
-archives
permanent
Q __ formalin _
.. f remaining ISSUe thawed
Fig.
2.
2.
.
paraffin. _ embedding
~. E.
'f ne7essary ._ special stallllng serial sectioning
paraffin section diagnosis
Standard method of intraoperative histological examination.
Complementary special methods used in specific cases
The standard method must be completed if special problems are to be solved, or certain tissues are to be interpreted (Table I). We have summarized in this table only the most important indications for intraoperative histochemical enzyme reactions as recommended by MEIER-RuGE in several papers. Further experiences will probably allow to enlarge the indications of these methods.
3. The necessity of immediate histological diagnosis A histological diagnosis must precede therapy. The intraoperative histological confirmation of the diagnosis is of major importance in all cases in which the preoperative morphologic identification of the disease has failed (for instance stenosis by diverticulitis of the sigmoid colon, or cancer). It is furthermore indicated if a laparotomy or a thoracotomy has given a surprising result, or if unexpected secondary diseases have been found. The histological confirmation of malignancy can be delayed before a radical operation only in those cases in which the same intervention would be carried out even if the lesion were benign (example: questionable malignant localized ulcerous lesion in the gastric antrum: aboral %-resection in case of a small gastric cancer as well as in case of a chronic peptic ulcer). If a lesion is accessible from the exterior, we should avoid a two-stage procedure with preliminary biopsy and definitive therapy some days later,
r06 . P. HERMANEK Table
1.
Complementary special methods of intraoperative examination
Question
Method
Hyperparathyroidism Hypo- and aganglionic megacolon Scirrhous cancer of stomach (resection lines, metastases) Brain tumors
SDH, LDH LDH
Organic hyperinsulinism
Calcified material
Tuberculosis suspected Bacterial suppurative inflammation? Gas gangrene? Tumors of adrenals and retroperitoneum Gout suspected
rapid histochemical enzyme reactions (MEIER-RuGE, WILLIGHAGEN, ZUGIBE)
leucine aminopeptidase
LDH, ATPase, alkaline phosphatase phase microscopy on random pancreas biopsy (W.H.BECKER) (rapid determination of alpha-beta cell relation without staining) standard method on lower temperature, rapid grinding method (VILLANUEVA and FROST), cytological smears (ZUGIBE), "bone cryostat" (PEARSE and GARDNER) acid fast staining of tissue smears
) g= ""ining of ,i,,"o
'mo~,
gross Henle chromo reaction, potassium iodate reaction (SHERWIN) murexid reaction on tissue
since preliminary biopsies are not completely harmless. Frozen section examination enables the surgeon to perform the biopsy and the radical operation at the same time (unitemporal or one-stage radical operation), that means to achieve the supreme aim of cancer surgery. This achievement is of special importance in malignant melanoma, in tumors of soft tissues, of bones, of salivary glands and thyroid. Frozen section examination is meant to provide a diagnosis; it enables the establishment of an adequate operation plan, and it guarantees the histological guidance of the surgical procedure. After a malignant tumor has been diagnosed, the question of its operability must be elucidated: nodular structures found on serous membranes, in the lung and the liver, and distant lymph nodes must be examined histologically, since a gross evaluation of such lesions is uncertain. Furthermore, local extension of the process must be confirmed by a histological examination, and the surgical intervention must be planned accordingly. The question whether fixation of a cancer of the rectum to the urinary bladder is due to an inflammatory reaction or a real neoplastic infiltration, cannot be solved by gross examination.
Intraoperative Histological Examination Today· 10 7
Finally, the radicality of surgery must be confirmed, especially in tumors having uncertain limits such as diffuse gastric cancers or solid cancers of the urinary bladder, and in malignant tumors that usually spread beyond the border seen macroscopically (oral cavity, esophagus, stomach, urinary bladder, prostate). The supreme aim to be achieved by the intraoperative histological examination is to do not too much but not too little in the presence of a malignant tumor. The histological control is of special importance in endocrine surgery. Whoever bases the surgical intervention in the case of hyperparathyroidism or of organic hyperinsulinism on gross findings only, will experience a failure. Endocrine surgery without immediate histological control is a hazardous procedure, if for instance after the removal of an "adenoma of the parathyroid" it becomes clear that it was in fact an adenoma of the thyroid gland, a lymph node or a thymic residue. Further problems of non-cancerous nature may arise, and should be mentioned here: diagnosis of tuberculosis (immediate tuberculostatic therapy, antituberculous disinfection measures taken in the operating room). If a sympathectomy should be performed: are the removed structures sympathetic ganglia? In case of a doubtful topographic situation on the pylorus: has the antral mucosa been totally removed with the gastric resection? Intestinal resection in case of aganglionosis or of Crohn's disease: must the resection be extended further? 4. The actual rapidity of frozen section examination In 200 non-selected examinations performed in 1972, the time has been measured exactly from the moment of the arrival of the tissue in the laboratory until the diagnosis was reported: the mean value was 2 minutes 38 seconds (minimum value I minute 40 seconds, maximum value 4 minutes 37 seconds). The transport from the operating room to the laboratory takes about I minute. The mean time from the moment in which the material is taken to the arrival of the diagnosis in the operating room is thus about 3 to 4 minutes. Under modern anesthesiologic conditions, the patient is not endangered even by several intraoperative histological examinations, since the duration of the surgical intervention is hardly increased, the more so as in many cases the surgeon can continue the operation while the histological examination is being carried out. 5. Errors and limits of the intraoperative histological examination It is quite clear that the degree of accuracy of frozen section diagnoses is lower than that of diagnoses based on sections of paraffin-embedded
108 . P. HERMANEK
material. The main reason can be explained as follows: intraoperative histological diagnosis is based on the examination of one or two sections only, special stains or histochemical reactions can not be regularily performed. The possibilities of the immediate histological diagnosis are thus limited, and the attention of the surgeon must be drawn to this fact once and again. Doubtful findings may be obtained with the frozen section method in those cases which may even be difficult to diagnose in permanent paraffinsections. As a rule, special problems must be solved by intraoperative histological examination, as for instance the question whether or not the lesion is malignant, whether the material has been taken from the antral or the duodenal mucosa, whether the parathyroids are normal, or adenomatous, or hyperplastic. The pathologist must answer these questions with a "Yes" or a "No" or "/ don't know". Detailed answers in all respects are not necessary under surgery. However, the fact that only one or two sections are examined cannot be overlooked, especially in the following situations: (a) Diagnosis of a malignant tumor that presents histological signs of malignancy in a limited zone only (mesenchymal tumors of the soft tissues and of the retroperitoneum, for instance highly differentiated liposarcoma and fibrosarcoma, highly differentiated adenocarcinomas of all organs and their metastases, well differentiated papillary carcinomas, early malignant melanomas). (b) Diagnosis of malignant tumors represented by very discrete formations (scirrhous cancers of stomach, pancreas or breast, micrometastases in lymph nodes or under the serosa). The immediate histological examination is not an appropriate method for the diagnosis of precancerous or early cancerous lesions of the breast and the cervix uteri. To make a differentiation between a pre cancer, a carcinoma in situ, a microcarcinoma and an advanced carcinoma, the entire specimen must have been embedded, and a great number of sections must have been examined. The same is true of the detailed classification of malignant tumors and of the grading of malignancy. If a high grade of malignancy has been found in focal carcinoma of locally removed intestinal polyps (poorly differentiated adenocarcinoma), a resection must be carried out even if the peduncle of the latter does not show invasion. The "limit of error" of frozen section examination has been studied frequently. By comparing the diagnosis of frozen section examination and of paraffin sections, the degree of histological accuracy can be established. The frequency of wrong positive findings is below I % according to most authors (mean value 0.38%). It was 0.15 % in our own material. The frequency of wrong negative findings and of doubtful cases is more vari-
Intraoperative Histological Examination Today' 109
able depending on the material to be examined and on the degree of accuracy of the examination of paraffin-embedded material. The pathologist who prepares only one section from the rest of the material used for frozen sections will record less wrong negative findings than after preparation of step-sections from the residual material. However, the "limits of clinical errors" are of greater importance, than the "limits of histological errors". By "limits of clinical errors", we understand the frequency of those cases in which the therapeutical procedure has not been influenced in the best way by frozen section diagnosis. This failure cannot be attributed exclusively to possible errors of the pathologist or to the inconvenience of the method, but it is also due to the fact that the surgeon has blundered somehow in taking the tissue for histological examination. We have statistically analyzed a total of 1,007 major operations with the following results: in 2 cases (0.2 %), the magnitude of the surgical intervention was too great, while in 4 cases (0.4 %), the extent of the intervention was too small. In 5 of these 6 cases, these faults were due to the fact that the surgeon had taken inadequate material for frozen section examination. In 7 cases (0.7 %), doubtful or wrong negative findings of the pathologist (doubtful findings in 6 cases of malignant melanoma, one wrong negative diagnosis in excision biopsy of the breast) delayed the final surgical therapy. We should like to emphasize that doubtful findings in frozen sections can often be clarified by repeated biopsies. In conclusion we may say that with an efficient collaboration of the team, the number of errors made in frozen section diagnosis that determines the practical activity of the surgeon, will be so low that they cannot be cited as an argument against this valuable method. 6. The prerequisites of an effective rapid histological diagnosis An effective frozen section diagnosis can only be realized in daily practice if the following five prerequisites are fulfilled: (a) In the laboratory, modern instruments must be at disposal: CO2 quick freeze chamber, cryostat microtome, both with spare units to be used in case of mechanical failure. (b) The transport of the tissue specimen from the operating room to the laboratory must not take more than 1 or 2 minutes. As a rule, the laboratory for rapid histological examinations is placed next to the operating room. If the laboratory is far away a pneumatic-tube plant must be provided. (c) A close collaboration must be established between the surgeon and the pathologist. This collaboration comprises regular informations of the
110 . P. HERMANEK
pathologist concerning the clinical history, the preoperative clinical findings, the macroscopic intraoperative findings, the special problems of the individual rapid histological examination, the mutual discussion about selection of the tissue specimen, and the conversation in case of doubtful histological findings. The pathologist must have been informed before the operation about the patient and his conditions. During the operation itself, a speaking equipment must be at hand between the surgeon and the pathologist. (d) The pathologist must have time for examination of frozen sections. In our opinion, it is absolutely necessary that during the regular operating hours a responsible pathologist keeps himself ready for immediate histological examinations, that means that he is free from other routine work. (e) Last not least: the pathologist must have acquired special experiences in frozen section diagnosis. This experience must be based "on frequent, one is tempted to say, dai!J use" (JENNINGS and LANDERS). If only 200 or 300 rapid histological diagnoses are made per annum in a laboratory, the necessary experiences cannot be acquired. An intensification of the frozen section method must be aimed at. The pathologist must not specialize in the rapid diagnostic method, since material embedded in paraffin must be studied routinely, and histological routine diagnoses must be performed by him. Even in large clinics and hospitals in Europe, these prerequisites are rarely fulfilled. However, both the pathologist and the surgeon must collaborate in the creation of an effective organization for immediate intraoperative histological examination. The aim of this organization is quite clear: the surgical activity must always be based upon histological findings, in favor of the patients.
Key-bibliography HERMANEK, P., BUNTE, H.: Die intraoperative Schnellschnittuntersuchung. Urban & Schwarzenberg, Miinchen-Berlin-Wien (1972) Prof. Dr. PAUL HERMANEK, D-852 Erlangen, Krankenhausstr. 10-12
lIO
(1973)
Review
Department of Clinical Pathology (Chief: Prof. Dr. P. HERMANEK), Surgical Clinic of the University of Erlangen-Nlirnberg (Chairman: Prof. Dr. G. HEGEMANN)
Intraoperative Histological Examination Today Intraoperative histologische Untersuchung heute P.
HERMANEK
With
2
Figures and
I
Table' Received January 3, 1973
In the beginning of our century, the immediate histological examination during surgery became a method of daily practice in several American hospitals. The principle has remained unchanged up to now: the activity of the surgeon must be based upon precise histopathologic information, because the macroscopic findings are often deceptive. Two reasons have induced us to deal once more with the problems of immediate histological examination for diagnostic purposes: (a) The important methodological improvements due to the introduction of the cryostat microtome into intraoperative diagnosis in 1957, and other complementary special methods are far from being generally used. (b) Owing to the constant improvement of surgical methods, the surgeon becomes more and more dependent on the cooperation with the pathologist. I.
The modern standard method
The introduction of the cryostat microtome has been the greatest methodological progress in the intraoperative histological examination. With this apparatus even a less skilled laboratory assistant can produce, within a few minutes, good sections of 6 or 8 [Lm, of native tissue (Fig. I). With the exception of calcified material, tissues of all kind can be properly sectioned by this method. If the cryostat microtome is used for sectioning purposes, the abrupt prefixation often carried out in former times (hot formol) can be abandoned. 8
Beitr. Path. Bd. 149
4 . P. HERMANEK
10
Fig. I. Carcinoma of the breast. Native tissue, cryostat microtome, polychrome methylene blue, non-permanent preparation. X 200.
Consequently, an exact cytological interpretation can be realized at high power magnification. In other words, the immediate freezing does not destroy the tissues to such an extent that later examination of the material embedded in paraffin does no more allow to make an exact diagnosis. LYNN and co-workers have shown that a modern frozen section examination can well be followed by an examination of the same tissue with the electron microscope. The question of the staining of specimens taken intraoperatively has not yet been settled. In the majority of the cases, a quick staining with polychrome methylene blue or other thiazine stains will be sufficient (Fig. I). Many authors and we, too, prefer this method for its rapidity. However, the pathologist who interprets the slides must be familiar with this sort of staining, that means that he must have seen it in many occasions. If an immediate intraoperative diagnosis is required, the shortest staining method must be chosen, that means a fast but unstable one. Time can be saved by short rinsing and covering with a 5 % glucose solution after staining (Fig. 2). Immediately after having made the diagnosis, another successive section can be performed and be treated in such a way that a permanent stain is obtained (fixation of the section, dehydration, inclusion in an anhydrous medium). This slide is used as a proof. As a rule, the materials examined intraoperatively must be embedded in paraffin. We proceed this way even in those cases in which the diagnosis is completely clear. This procedure enables us to make further sections at any moment, and to investigate the material at a later moment in order to clarify scientific problems.
Intraoperative Histological Examination Today· 10 5
bI
I-Itltl-U thiazins
section 1
~-- I CJ I
hematoxylin·eosin
secti,on 2
I
diagnOSIs
not permanent
cryostat mICrotome \
fr~zen s.ec1ion
CJ
7-tl tjtltl
-archives
permanent
Q __ formalin _
.. f remaining ISSUe thawed
Fig.
2.
2.
.
paraffin. _ embedding
~. E.
'f ne7essary ._ special stallllng serial sectioning
paraffin section diagnosis
Standard method of intraoperative histological examination.
Complementary special methods used in specific cases
The standard method must be completed if special problems are to be solved, or certain tissues are to be interpreted (Table I). We have summarized in this table only the most important indications for intraoperative histochemical enzyme reactions as recommended by MEIER-RuGE in several papers. Further experiences will probably allow to enlarge the indications of these methods.
3. The necessity of immediate histological diagnosis A histological diagnosis must precede therapy. The intraoperative histological confirmation of the diagnosis is of major importance in all cases in which the preoperative morphologic identification of the disease has failed (for instance stenosis by diverticulitis of the sigmoid colon, or cancer). It is furthermore indicated if a laparotomy or a thoracotomy has given a surprising result, or if unexpected secondary diseases have been found. The histological confirmation of malignancy can be delayed before a radical operation only in those cases in which the same intervention would be carried out even if the lesion were benign (example: questionable malignant localized ulcerous lesion in the gastric antrum: aboral %-resection in case of a small gastric cancer as well as in case of a chronic peptic ulcer). If a lesion is accessible from the exterior, we should avoid a two-stage procedure with preliminary biopsy and definitive therapy some days later,
r06 . P. HERMANEK Table
1.
Complementary special methods of intraoperative examination
Question
Method
Hyperparathyroidism Hypo- and aganglionic megacolon Scirrhous cancer of stomach (resection lines, metastases) Brain tumors
SDH, LDH LDH
Organic hyperinsulinism
Calcified material
Tuberculosis suspected Bacterial suppurative inflammation? Gas gangrene? Tumors of adrenals and retroperitoneum Gout suspected
rapid histochemical enzyme reactions (MEIER-RuGE, WILLIGHAGEN, ZUGIBE)
leucine aminopeptidase
LDH, ATPase, alkaline phosphatase phase microscopy on random pancreas biopsy (W.H.BECKER) (rapid determination of alpha-beta cell relation without staining) standard method on lower temperature, rapid grinding method (VILLANUEVA and FROST), cytological smears (ZUGIBE), "bone cryostat" (PEARSE and GARDNER) acid fast staining of tissue smears
) g= ""ining of ,i,,"o
'mo~,
gross Henle chromo reaction, potassium iodate reaction (SHERWIN) murexid reaction on tissue
since preliminary biopsies are not completely harmless. Frozen section examination enables the surgeon to perform the biopsy and the radical operation at the same time (unitemporal or one-stage radical operation), that means to achieve the supreme aim of cancer surgery. This achievement is of special importance in malignant melanoma, in tumors of soft tissues, of bones, of salivary glands and thyroid. Frozen section examination is meant to provide a diagnosis; it enables the establishment of an adequate operation plan, and it guarantees the histological guidance of the surgical procedure. After a malignant tumor has been diagnosed, the question of its operability must be elucidated: nodular structures found on serous membranes, in the lung and the liver, and distant lymph nodes must be examined histologically, since a gross evaluation of such lesions is uncertain. Furthermore, local extension of the process must be confirmed by a histological examination, and the surgical intervention must be planned accordingly. The question whether fixation of a cancer of the rectum to the urinary bladder is due to an inflammatory reaction or a real neoplastic infiltration, cannot be solved by gross examination.
Intraoperative Histological Examination Today· 10 7
Finally, the radicality of surgery must be confirmed, especially in tumors having uncertain limits such as diffuse gastric cancers or solid cancers of the urinary bladder, and in malignant tumors that usually spread beyond the border seen macroscopically (oral cavity, esophagus, stomach, urinary bladder, prostate). The supreme aim to be achieved by the intraoperative histological examination is to do not too much but not too little in the presence of a malignant tumor. The histological control is of special importance in endocrine surgery. Whoever bases the surgical intervention in the case of hyperparathyroidism or of organic hyperinsulinism on gross findings only, will experience a failure. Endocrine surgery without immediate histological control is a hazardous procedure, if for instance after the removal of an "adenoma of the parathyroid" it becomes clear that it was in fact an adenoma of the thyroid gland, a lymph node or a thymic residue. Further problems of non-cancerous nature may arise, and should be mentioned here: diagnosis of tuberculosis (immediate tuberculostatic therapy, antituberculous disinfection measures taken in the operating room). If a sympathectomy should be performed: are the removed structures sympathetic ganglia? In case of a doubtful topographic situation on the pylorus: has the antral mucosa been totally removed with the gastric resection? Intestinal resection in case of aganglionosis or of Crohn's disease: must the resection be extended further? 4. The actual rapidity of frozen section examination In 200 non-selected examinations performed in 1972, the time has been measured exactly from the moment of the arrival of the tissue in the laboratory until the diagnosis was reported: the mean value was 2 minutes 38 seconds (minimum value I minute 40 seconds, maximum value 4 minutes 37 seconds). The transport from the operating room to the laboratory takes about I minute. The mean time from the moment in which the material is taken to the arrival of the diagnosis in the operating room is thus about 3 to 4 minutes. Under modern anesthesiologic conditions, the patient is not endangered even by several intraoperative histological examinations, since the duration of the surgical intervention is hardly increased, the more so as in many cases the surgeon can continue the operation while the histological examination is being carried out. 5. Errors and limits of the intraoperative histological examination It is quite clear that the degree of accuracy of frozen section diagnoses is lower than that of diagnoses based on sections of paraffin-embedded
108 . P. HERMANEK
material. The main reason can be explained as follows: intraoperative histological diagnosis is based on the examination of one or two sections only, special stains or histochemical reactions can not be regularily performed. The possibilities of the immediate histological diagnosis are thus limited, and the attention of the surgeon must be drawn to this fact once and again. Doubtful findings may be obtained with the frozen section method in those cases which may even be difficult to diagnose in permanent paraffinsections. As a rule, special problems must be solved by intraoperative histological examination, as for instance the question whether or not the lesion is malignant, whether the material has been taken from the antral or the duodenal mucosa, whether the parathyroids are normal, or adenomatous, or hyperplastic. The pathologist must answer these questions with a "Yes" or a "No" or "/ don't know". Detailed answers in all respects are not necessary under surgery. However, the fact that only one or two sections are examined cannot be overlooked, especially in the following situations: (a) Diagnosis of a malignant tumor that presents histological signs of malignancy in a limited zone only (mesenchymal tumors of the soft tissues and of the retroperitoneum, for instance highly differentiated liposarcoma and fibrosarcoma, highly differentiated adenocarcinomas of all organs and their metastases, well differentiated papillary carcinomas, early malignant melanomas). (b) Diagnosis of malignant tumors represented by very discrete formations (scirrhous cancers of stomach, pancreas or breast, micrometastases in lymph nodes or under the serosa). The immediate histological examination is not an appropriate method for the diagnosis of precancerous or early cancerous lesions of the breast and the cervix uteri. To make a differentiation between a pre cancer, a carcinoma in situ, a microcarcinoma and an advanced carcinoma, the entire specimen must have been embedded, and a great number of sections must have been examined. The same is true of the detailed classification of malignant tumors and of the grading of malignancy. If a high grade of malignancy has been found in focal carcinoma of locally removed intestinal polyps (poorly differentiated adenocarcinoma), a resection must be carried out even if the peduncle of the latter does not show invasion. The "limit of error" of frozen section examination has been studied frequently. By comparing the diagnosis of frozen section examination and of paraffin sections, the degree of histological accuracy can be established. The frequency of wrong positive findings is below I % according to most authors (mean value 0.38%). It was 0.15 % in our own material. The frequency of wrong negative findings and of doubtful cases is more vari-
Intraoperative Histological Examination Today' 109
able depending on the material to be examined and on the degree of accuracy of the examination of paraffin-embedded material. The pathologist who prepares only one section from the rest of the material used for frozen sections will record less wrong negative findings than after preparation of step-sections from the residual material. However, the "limits of clinical errors" are of greater importance, than the "limits of histological errors". By "limits of clinical errors", we understand the frequency of those cases in which the therapeutical procedure has not been influenced in the best way by frozen section diagnosis. This failure cannot be attributed exclusively to possible errors of the pathologist or to the inconvenience of the method, but it is also due to the fact that the surgeon has blundered somehow in taking the tissue for histological examination. We have statistically analyzed a total of 1,007 major operations with the following results: in 2 cases (0.2 %), the magnitude of the surgical intervention was too great, while in 4 cases (0.4 %), the extent of the intervention was too small. In 5 of these 6 cases, these faults were due to the fact that the surgeon had taken inadequate material for frozen section examination. In 7 cases (0.7 %), doubtful or wrong negative findings of the pathologist (doubtful findings in 6 cases of malignant melanoma, one wrong negative diagnosis in excision biopsy of the breast) delayed the final surgical therapy. We should like to emphasize that doubtful findings in frozen sections can often be clarified by repeated biopsies. In conclusion we may say that with an efficient collaboration of the team, the number of errors made in frozen section diagnosis that determines the practical activity of the surgeon, will be so low that they cannot be cited as an argument against this valuable method. 6. The prerequisites of an effective rapid histological diagnosis An effective frozen section diagnosis can only be realized in daily practice if the following five prerequisites are fulfilled: (a) In the laboratory, modern instruments must be at disposal: CO2 quick freeze chamber, cryostat microtome, both with spare units to be used in case of mechanical failure. (b) The transport of the tissue specimen from the operating room to the laboratory must not take more than 1 or 2 minutes. As a rule, the laboratory for rapid histological examinations is placed next to the operating room. If the laboratory is far away a pneumatic-tube plant must be provided. (c) A close collaboration must be established between the surgeon and the pathologist. This collaboration comprises regular informations of the
110 . P. HERMANEK
pathologist concerning the clinical history, the preoperative clinical findings, the macroscopic intraoperative findings, the special problems of the individual rapid histological examination, the mutual discussion about selection of the tissue specimen, and the conversation in case of doubtful histological findings. The pathologist must have been informed before the operation about the patient and his conditions. During the operation itself, a speaking equipment must be at hand between the surgeon and the pathologist. (d) The pathologist must have time for examination of frozen sections. In our opinion, it is absolutely necessary that during the regular operating hours a responsible pathologist keeps himself ready for immediate histological examinations, that means that he is free from other routine work. (e) Last not least: the pathologist must have acquired special experiences in frozen section diagnosis. This experience must be based "on frequent, one is tempted to say, dai!J use" (JENNINGS and LANDERS). If only 200 or 300 rapid histological diagnoses are made per annum in a laboratory, the necessary experiences cannot be acquired. An intensification of the frozen section method must be aimed at. The pathologist must not specialize in the rapid diagnostic method, since material embedded in paraffin must be studied routinely, and histological routine diagnoses must be performed by him. Even in large clinics and hospitals in Europe, these prerequisites are rarely fulfilled. However, both the pathologist and the surgeon must collaborate in the creation of an effective organization for immediate intraoperative histological examination. The aim of this organization is quite clear: the surgical activity must always be based upon histological findings, in favor of the patients.
Key-bibliography HERMANEK, P., BUNTE, H.: Die intraoperative Schnellschnittuntersuchung. Urban & Schwarzenberg, Miinchen-Berlin-Wien (1972) Prof. Dr. PAUL HERMANEK, D-852 Erlangen, Krankenhausstr. 10-12