1 JClin Pathol 1994;47:714-717

Cytopathology in the post mortem room

E Walker, J J Going

AbstractAim-To demonstrate the role ofcytopathology in examining tumoursfound at post mortem examination.Methods-Tumour deposits were foundin 25 hospital necropsies. Cytologicaldiagnosis made at the time of necropsywas compared with subsequent paraffinwax embedded histological sections.Results-In 19 out of 20 cases with noprevious histological diagnosis, cytologyat the time of necropsy provided rapidand accurate assessment of tumour type.Subsequent histological examination offormalin fixed material merely refinedthe diagnosis in some cases. In theremaining five cases in which tumourtype was known, cytological examinationof deposits found at necropsy providedextra information that was useful forcompiling a provisional report.Conclusions-Rapid cytological exami-nation of tumours found during postmortem examinations provides accuraterelevant information which can be usedto produce a more comprehensive provi-sional necropsy report. The techniquehas advantages over frozen sectionhistology and can provide useful cyto-logical experience for histopathologytrainees.

(7 Clin Pathol 1994;47:714-717)

MethodsA series of 25 recent routine hospital necropsycases illustrates the use of cytology in the postmortem room in a variety of situations.Relevant clinical data and necropsy findingsare given in the table. Although most of thesecases were included because they deal withpreviously undiagnosed tumours, some casesillustrate the use of cytology in which therewas recognised tumour with specific diagno-sis, but some question arising at the time ofnecropsy required clarification. Cases werenot chosen merely because cytological andhistological diagnoses were in agreement.

Slides were prepared using "scrape cytol-ogy".' A freshly cut surface of tumour wasscraped gently with a clean scalpel blade. Theresulting fluid with tumour cells was dottedon to one end of a glass slide and a smear ofthe material made with a second clean slide inthe conventional manner. Such smears weretreated in two ways. Air dried smears werefixed and stained using the Diff Quik method(Baxter Healthcare Ltd). Smears fixed imme-diately in 95% ethanol for one to two minuteswere stained using haematoxylin and eosin.Preparation time by the Diff Quik methodwas up to five minutes while haematoxylinand eosin stained slides took about 10 min-utes. Alcohol fixed smears were also used forglycogen or mucin staining using conven-tional periodic acid Schiff (PAS) or PAS-diastase methods, respectively.

Department ofPathology, RoyalInfirmary, CastleStreet, GlasgowG4 OSFE WalkerJ J GoingCorrespondence to:Dr Eric Walker

Accepted for publication9 February 1994

Hospital necropsies are often performed onpatients with malignant tumours. Despite thesophistication of modem methods of investi-gation, many necropsies reveal undiagnosedor even unsuspected tumours. Of 223 routinehospital necropsies carried out during 1992 atGlasgow Royal Infirmary, 64 (28 7%) showedmalignant tumours, 40 (62 5%) with no priorhistological or cytological diagnosis and 25(39%) unsuspected clinically. Pathologistsshould, whenever possible, provide a micro-scopic assessment of such previously undiag-nosed tumours at the time of necropsy.Usually frozen section histology is suitable fortyping such tumours. However, this has dis-advantages when applied to necropsy mater-ial. The technique requires an MLSO's timeand therefore usually only a single samplefrom one site is examined. Necropsy frozensections are often of poor quality and there is arisk of cryostat contamination with infectiveagents.

ResultsIn general the quality of necropsy based cyto-logical material was good, in some cases it wasactually better than tissue retained for con-ventional paraffin wax histology. It was usefulto have both air dried and alcohol fixed mate-rial. Although staining by the Diff Quikmethod was the most rapid, alcohol fixedsmears were useful for special stains such asPAS-diastase for mucin.The table summarises the clinical and

necropsy details together with cytological andhistological findings in the 25 cases. Twentyconcern patients with no previous pathologi-cal diagnosis of tumour. These cases illustratetypical problems for which rapid confirmationof tumour type is desirable for the productionof a relatively complete report on the day ofnecropsy.The cases fall into distinct categories. Cases

1-5 demonstrate the assessment of lungtumours. This is useful where multiple or

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Cytopathology in the post mortem room

Details of cases coming to necropsy with post mortem and subsequent histologicalfindingsCase No(sex, age)

1 (M, 80)*t

2 (M, 56)*

3 (F, 58)*t4 (M, 72)*5 (M, 68)*6 (F, 84)*t7 (F, 63)*

8 (M, 53)*

9 (M, 86)*10 (M, 49)*t11 (M, 74)*12 (M, 64)*t

13 (F, 85)*t

14 (M, 77)*t

15 (F, 67)*

16 (F, 96)*t

17 (F, 72)*t

18 (M, 61)*

19 (M, 70)*t

20 (F, 83)*t21 (M, 54)

22 (M, 49)

Gross findings at necropsy

Widespread tumour, unilateral lungdeposits

Widespread tumour, bilateral lungdeposits

Lung tumour, widespread metastasesLung tumour, widespread metastases

Lung tumourGastric tumour, hepatic metastasesSclerotic mass in left lobe of liver,

multiple deposits in right lobeIntraabdominal metastases,

small mass in pancreasMultiple hepatic depositsWidespread tumourWidespread tumour, mass in rectumWidespread tumour, small nodule in

pancreasThickened gallbladder with obliteration of

lumenFocal constriction of ascending colon

Clinical suspicion of bone metastases.No gross tumour at autopsy? microscopic tumour in marrow

Large bowel and renal tumours

Generalised lymphadenopathy,hepatosplenomegaly

Hilar lymphadenopathy, splenomegaly,multiple hepatic deposits

Retroperitoneal mass, myocardialdeposits

Mass arising from gastric greater curveKnown adenoid cystic carcinoma.

Sclerotic mass around left temporal boneKnown non-Hodgkin's lymphoma.Lymph node and hepatic deposits

23 (M, 59) Previous squamous carcinoma ofoesophagus and second primary rectaladenocarcinoma. Widespread tumour

24 (M, 67) Previous bladder carcinoma, Caecal tumour,renal tumour and widespread metastases

25 (M, 56) Previous small bowel carcinoid.Widespread tumour

Cytological diagnosisat time of necropsy

Small cell carcinoma

Small cell carcinoma

Small cell carcinomaPoorly differentiated

non-small cell carcinomaAdenocarcinomaAdenocarcinomaProbable intrahepatic

cholangiocarcinomaAdenocarcinoma

Hepatocellular carcinomaRenal carcinomaAdenocarcinomaAdenocarcinoma

Adenocarcinoma

Carcinoma

No tumour identified

Separate primary colonicand renal carcinomas

Non-Hodgkin's lymphoma

Lymphoma, possiblyHodgkin's lymphoma

Non-Hodgkin's lymphoma

Benign stromal tumourRecurrent adenoid cystic

carcinomaRecurrent lymphoma

Metastatic adenocarcinoma

(i) Primary caecaladenocarcinoma

(ii) Primary renal carcinoma(iii) Metastases from caecal

adenocarcinomaMetastatic carcinoid tumour

Subsequent paraffin waxembedded histology

Confirms cytology

Confirms cytology

Confirms cytologyLarge cell undifferentiated

carcinomaConfirms cytologyConfirms cytology

Confirms cytologyConfirms cytology

Confirms cytologyConfirms cytologyConfirms cytologyConfirms cytology

Confirms cytology

Moderately differentiatedadenocarcinoma

Metastatic undifferentiatedcarcinoma ? source

Confirms cytology

Non-Hodgkin's lymphoma-small B cell type

Lymphocyte predominantHodgkin's lymphoma

Non-Hodgkin's lymphoma-centroblastic type

Confirms cytologyConfirms cytology

Probable anaplastictransformation of previousnon-Hodgkin's lymphoma

Confirms cytology

Confirms cytology

Confirms cytology

*No previous histological or cytological diagnosis; urumour unsuspected clinically.

Figure 1 Case 2: primary bronchial small cell carcinoma(haematoxylin and eosin).

Figure 2 Case 9: primary hepatocellular carcinoma(haematoxylin and eosin).

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Walker, Going

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Figure 3 Case 15: metastatic undifferentiated carcinomain bone marrow (DiffQuik).

bilateral tumour deposits are present andthere is doubt as to whether these are from aprimary lung tumour. Case 2 (fig 1) illustratesa primary small cell carcinoma of lung

*L

with multiple bilateral pulmonary metastases.Cases 6-12 illustrate similar problems of

multiple intraabdominal tumour deposits.Multiple hepatic tumour deposits do not nec-essarily indicate metastases (case 9) (fig 2).Typing of hepatic metastatic tumour depositscan also suggest likely sites of an elusive smallprimary-as in case 12.

Indistinct gross tumour deposits whichmight otherwise be taken for inflammatorylesions can be examined rapidly by cytology(cases 13 and 14). In case 15 bone metastaseswere suspected clinically but no histologicaldiagnosis had been made and no grosstumour deposits were evident at necropsy. Atthe time of necropsy no malignant cells werenoted in cytological smears made from bonemarrow. In retrospect, undifferentiated carci-noma cells were present in these smears (fig3). Two previously undiagnosed separate pri-mary carcinomas (case 16) (fig 4) were clearlyresolved by cytological examination. Stainingusing PAS with and without diastase on alco-hol fixed smears proved particularly useful inthis case.

Several previously undiagnosed lymphomaswere encountered and these were differenti-ated from carcinomas (cases 17-19) (fig 5).One benign tumour found during the exami-nation was diagnosed using scrape cytology(case 20).

Rapid confirmation of the nature of tumourdeposits also proved useful in many cases withprevious histological diagnoses (cases 21-25)allowing the pathologist to give a more com-prehensive preliminary necropsy report.

W.WM_

i' R

Figure 4 Case 16: (A) primary colonic adenocarcinoma; (B) primary clear cell renal carcinoma (haematoxylin andeosin).

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,ytopathology in the post mortem room

,igure S Case 19:setastatic non-Hodgkin'svmphoma in myocardiumlhaematoxylin and eosin).

DiscussionHospital necropsy rates have been in declinefor years.2 The reasons for this are manyfoldand include the attitudes of clinicians, pathol-ogists, and relatives.'4 Pathologists have toensure that the necropsy is carried out rapidlyand efficiently and that provisional and finalreports are issued promptly. Issue of the finalreport, taking into account histological find-ings, is often delayed.5 There is a rapid declinein interest in the post mortem examinationafter gross findings have been discussed withclinicians. Consequently every effort shouldbe made to provide as much relevant informa-tion as possible at the time of the necropsy.This is particularly true where unexpectedpathology is uncovered such as previouslyundiagnosed tumours. Such cases accountedfor up to 63% of post mortem examinationsinvolving malignant tumours at GlasgowRoyal Infirmary during 1992.

Investigation of undiagnosed or unsus-pected tumours by frozen section has disad-vantages. The technique is time consumingfor MLSO staffwho may have legitimate con-cerns about the infective potential of necropsymaterial. To sample more than one lesiondemands further time. The quality ofnecropsy frozen sections is often poor andspecial stains-for example, for mucin-areusually inconvenient.We have shown that cytological examina-

tion of tumours at the time of necropsy hasadvantages over frozen section. The techniqueis rapid and can be performed by the patholo-gist without MLSO support. Multiple sites oftumour, including bone marrow, can be sam-pled, stained, and assessed quickly and specialstains for mucin performed in poorly differen-tiated lesions. The quality of cytological mate-rial is generally good, often better than frozenor even paraffin wax sections. Fixation andstaining in the post mortem suite eliminatesthe risk of laboratory and cryostat contamina-tion with infective organisms. Small lesionscan be sampled without destroying them,thereby permitting demonstration of completespecimens and ultimately paraffin waxembedded histology. Finally, regular exposureto more and varied cytological material shouldbe beneficial to all histopathology trainees.

Cytological examination of tumours is arapid, accurate diagnostic technique for usewith surgical specimens,6 but cytological tech-niques are appropriate to autopsy practice. Ofseveral advantages, the ability to provide arapid, accurate, and comprehensive provi-sional necropsy report is perhaps the greatest,and may help to stimulate an increase inrequests for necropsies.

1 Howat AJ, Williams RA. Combined scrape cytology andfrozen section histology for rapid diagnosis in breastpathology. Histopathology 1990;17:85-96.

2 Hill RB, Anderson RE. Pathologists and the autopsy. AmJClin Pathol 1991;95(Suppl 1):S42-S9.

3 Stubbs F, Start RD, Hector-Taylor MJ, Cotton DWK.The attitudes of junior pathologists towards the autopsy.J Pathol 1992;166:413-5.

4 Champ C, Tyler X, Andrews PS, Coghill SB. Improveyour hospital autopsy rate to 40-50 per cent, a tale oftwo towns. JPathol 1992;166:405-7.

5 Whitty P, Parker C, Prieto-Ramos F, Al-Kharusi S.Communication of results of necropsies in North EastThames region. BMJ 1991;303: 1244-6.

6 Sidawy MK, Silverberg SG. Intraoperative cytology. Backto the future?Am JClin Pathol 1991;96:1-3.

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