388.8 Clin Pathol 1993;46:388-393

I J Clin Pathol: first published as 10.1136/jcp.46.5.388 on 1 May 1993. Downloaded from ACP Broadsheet No 138 May 1993

Gross examination of uterine specimens

J Scurry, K Patel, M Wells

Introduction CERVICAL PUNCH BIOPSY Gynaecological specimens form a substantial Colposcopic cervical punch biopsy specimens proportion of the workload in most depart- are used to evaluate cervical intraepithelial ments. The aim of this broadsheet is to assist neoplasia (CIN) and human papillomavirus in the macroscopic description and handling (HPV) . Punch biopsy specimens are of uterine specimens (table) to provide opti- pale tissue fragments 2-3 mm in maximum mal sections for microscopic examination. dimension. They are completely transferred Uteri are best received unfixed, particularly to the processing cassette, where they are pro- in patients with cancer. Not only can appro- tected from loss by being sandwiched priate tissue be selected and optimally between foam pads. Although there are tech- processed for special investigations, including niques for orientation when cassetting, orien- hormone receptors, electron microscopy, tation is quite satisfactorily performed at the cytology imprints and some types of immuno- time of paraffin wax embedding. Levels histochemistry, but the fresh specimen is should be cut. better for macroscopic description and pre- paration for demonstration at clinicopatho- CERVICAL WEDGE BIOPSY

logical meetings and macrophotography. These larger cervical biopsy specimens are http://jcp.bmj.com/ Endometrial autolysis occurs rapidly when taken to confirm an overtly invasive (at least incompletely opened or unopened uteri have stage lb) cervical carcinoma before definitive been left in fixative in the operating treatment, or as an alternative to a punch theatre or laboratory. Formalin penetrates biopsy specimen. Wedge biopsy specimens solid tissue very slowly from the exterior, and are up to 1 cm or more in maximum dimen- for practical purposes does not enter the uter- sion, and should be measured as a surface

ine cavity. Tissue beyond a few millimetres area and a depth. They are sliced perpendicu- on September 28, 2021 by guest. Protected copyright. from a formalin bathed surface autolyses larly to the surface at 2-3 mm intervals, before it fixes. Pre-warmed formalin is best preferably in the long axis of the . The This Broadsheet has been not used to quicken fixation of uteri contain- long axis can be identified by the presence of prepared by the authors at the invitation ofthe Association of ing cancer as heat exacerbates the autolytic longitudinal endocervical grooves. Clinical Pathologists who process of tissue not in contact with formalin. reserve the copyright. Further copies of this Broadsheet may Endometrial curettings may be fixed in be obtainedfrom the Bouin's solution, which gives better cytologi- Publishing Manager, journal ofClinical , BMA cal preservation, particularly of the endome- Uterine specimens House, Tavistock Square, trial stroma. London WCIH 9JR Types ofuterine specimens Department of Cervical Anatomical specimens Cervical specimens: ENDOCERVICAL POLYPECTOMY Endocervical polypectomy Pathology, Mercy Manchester repair Hospital for Women, Most cervical polyps are benign endocervical Cervical punch biopsy Melbourne, Australia mucosal polyps. These are smooth surfaced, Cervical wedge biopsy J Scurry Cervical cone biopsy slippery, pedunculated and typically 1-2 cm Large loop excision of the transformation zone (LLETZ) Department of Endocervical curettings , The in diameter. Small polyps are bisected and all are submitted. With is Endometnal specimens: General Infirmary at large polyps, sampling Endometrial curentings Leeds, Leeds sufficient. Uterine aspiration K Patel Endometrial resection Academic Unit of MANCHESTER REPAIR Myometnial specimens: Pathology, Myomectomy Department of Manchester repairs are performed for pro- specimens: Clinical Medicine, lapse. The specimen consists of an amputated No macroscopic abnormality University of Leeds, cervix, with one or two attached triangular Benign conditions Leeds LS2 9JT Cervical intraepithelial neoplasia, past or present fragments of . These specimens are Cervical cancer M Wells Endometrial cancer Accepted for publication sent to pathology for audit purposes and pre- 7 August 1992. sent little diagnostic challenge. Gross examination ofuterine specimens 389

CERVICAL CONE BIOPSY men is usually a cylindrical or coin shaped A cervical cone biopsy is performed to con- specimen consisting of ectocervix, endocervi- firm and possibly treat microinvasive carcino- cal canal, and stroma. The diameter of the

ma or to investigate a high grade abnormal biopsy specimen, the measurements of the os, J Clin Pathol: first published as 10.1136/jcp.46.5.388 on 1 May 1993. Downloaded from smear, where the lesion or the upper extremi- and the length should be recorded. The biop- ty of a lesion cannot be seen at . sy specimen may have an orientating suture, The diameter of the ectocervix, the mea- usually marking the anterior lip. If so, the surements of the os, and the length should be stroma of this half should be marked with ink recorded. The appearance of the ecto- and or silver nitrate. There is no need to mark the endocervical mucosa should be noted. There resection lines as they can be identified histo- are several methods for dissecting a cone logically by looking for diathermy artefact. biopsy specimen. A common approach is to The biopsy specimen should be fixed whole fix the cone whole, mark the stroma with ink and divided at 2-3 mm intervals into num- or silver nitrate, then slice it parasagittally at bered parasagittal slices. Levels are not rou- 2-3 mm intervals, beginning at 3 o'clock or 9 tinely cut. o'clock (fig 1A). If the cone biopsy specimen Occasionally, tissue is removed in a step- is received fresh, an alternative method can wise manner resulting in numerous fragments be used. The cone is opened at 12 o'clock, termed cervical chippings. These should be pinned out, fixed for at least 2 hours, then weighed and all the material embedded. divided into longitudinal strips at 0.2-0.3 cm Where possible, fragments containing part (or intervals, beginning at 12 o'clock and pro- the entire) cervical os should be identified gressing clockwise (fig iB). Radial or coronal and embedded separately. This will ensure sectioning of the fixed cone are not recom- that the squamocolumnar junction is ade- mended as the radial method can result in quately sampled. loss of epithelium and the coronal method Diathermy artefact in biopsy specimens does not give a good view of the transforma- derived using LLETZ can make handling and tion zone. Longitudinal blocks of cone biopsy interpretation of the specimens troublesome, specimens longer than 2.5 cm will not fit easi- if not impossible. Difficulty in orientation of ly into a cassette whatever method is used. cervical chippings means that adequacy of Long cones, whether arriving fixed or fresh, excision cannot usually be commented on should therefore be shortened by having the when tissue is removed in this manner. apical, and if necessary, subjacent coronal blocks, taken before opening. The routine ENDOCERVICAL CURETrINGS taking of a coronal apical block in normal Endocervical curettage is performed to evalu- sized cones, however, is not recommended, as ate the presence of intraepithelial neoplasia coronal blocks give a tangential view of the (squamous or glandular) in the endocervical

resection line that is not as accurate as a per- canal. The curettings typically consist of a http://jcp.bmj.com/ pendicular view given by longitudinal blocks. small quantity of mucus and blood in which strands of pale tissue can be seen. Like punch LARGE LOOP EXCISION OF THE biopsy specimens endometrial curettings may TRANSFORMATION ZONE (LLETZ) be processed between foam pads. At embed- LLETZ biopsy specimens, taken under local ding, the tissue fragments and residual mucus anaesthesia are being increasingly used to are picked out by fine forceps. Alternatively,

diagnose and treat CIN.' The procedure the curettings may be processed wrapped up on September 28, 2021 by guest. Protected copyright. involves removal of tissue by means of a in filter paper, although, at embedding, there diathermy effect generated at the end of a may be difficulty separating tissue strands long wire loop. The resulting biopsy speci- from paper fibres.

Figure 1 Methods for blocking ofa cone biopsy specimen. (A) Parasagittal blocking ofthe whole fixed cone biopsy specimen. (B) longitudinal blocking ofthe opened, pinned out cone biopsy specimen (El: End piece, usually not embedded).

(A) (B) 390 Scurry, Patel, Wells

Endometrial specimens ENDOMETRIAL ASPIRATION ENDOMETRIAL CURET'INGS Another increasingly popular technique in Endometrial curettage is performed in the gynaecological practice is the aspiration of

investigation of abnormal uterine bleeding or through a tube or pipette. The J Clin Pathol: first published as 10.1136/jcp.46.5.388 on 1 May 1993. Downloaded from infertility, or as a diagnostic and therapeutic main advantage of this procedure is that cer- procedure in abortion. vical dilatation and therefore anaesthesia is not required. The disadvantage is that the Non-gestational curettings specimen is very small and may be unsatisfac- Normal endometrial curettings are strips of tory and contain no endometrium. A good soft pink tissue mixed with blood clot and aspirate specimen appears as a variegated mucus. Their volume can be quite satisfacto- core composed of tissue, blood, and mucus, rily estimated in a semiquantitative way as of 2-3 mm in diameter and several centime- small, medium, or large, or for the more tres long. These specimens are all submitted obsessional, in cubic centimetres, or even and processed between foam pads and report- weighed. Curettings derived from normal ed like curettings. proliferative and early secretory endometrium seldom fill more than one cassette. If more than one cassette is required, late secretory Myometrial specimens endometrium, , malignancy or MYOMECTOMY pregnancy should be suspected. Polypoid Myomectomy specimens are sent for pieces may be identified in the curettings, but histopathology to confirm the clinical diagno- the definitive diagnosis of an endometrial sis of leiomyoma and to exclude malignancy. polyp should await histological examination. Any deviation from the typical macroscopic Friable or firm yellowish tissue is abnormal appearance of a pale firm lesion with a white and characteristic of endometrial carcinoma. whorled cut surface should be noted and the If fat is identified macroscopically, it has most abnormal tissue submitted for histological likely come from the peritoneal cavity examination. Soft areas are particularly suspi- through a uterine perforation, and the clini- cious of malignancy. Myomectomy specimens cian should be warned of this possibility with- should be weighed, measured, and sliced at out delay. To exclude malignancy, all the 0-5 to 1 cm intervals. Routine sampling curettings must be embedded. should include one block per leiomyoma, up to three blocks. Gestational curettings In gestational cases the aim of the curettage is to confirm pregnancy and to exclude tro- Hysterectomy specimens phoblastic . A careful macroscopic The should be weighed (after removal

search for products of conception looking for of adnexal structures), measured, and opened http://jcp.bmj.com/ spongy tissue representing chorionic villi, a to expose the endometrium for adequate fixa- thin walled intact or disrupted cyst represent- tion. Note that the parous uterus (pre- ing the gestational sac, and fetal parts is menopausal adult 75-100 g) is heavier than required. Products of conception per se are the nulliparous uterus (premenopausal adult often outweighed by blood clot; dark red 30-40 g), and weight increases with parity, so haemorrhagic thickened membranous tissue, that after eight pregnancies a weight of 240 g

with one shiny and one rough surface repre- is normal.2 Measurements for normal pre- on September 28, 2021 by guest. Protected copyright. senting decidua and pink soft tissue, repre- menopausal adults are: length (top of fundus senting hypersecretory endometrium. In to ectocervix) 5-8 cm; width (intercomual abortion abundant curettings are usually distance) 3-5 cm; length and diameter of obtained; their quantity can be recorded by cervix both 3 cm.2 The uterus may be orien- weighing. Only sampling, with emphasis on tated by (1) the "peritoneal" reflection being submitting probable products of conception, higher anteriorly to accommodate the bladder is practical. Two full cassettes are adequate, and (2) the observation that the round liga- but if molar change is suspected further sam- ment is the most anterior, followed by the fal- pling should be undertaken. lopian tube, followed by the . The uterus may be impossible to orientate if it is grossly distorted by fibroids, or where much ENDOMETRIAL RESECTION of the peritoneal surface is missing and no Endoscopic resection of the endometrium is adnexal stumps are recognised, as occurs in increasingly used as a treatment for dysfunc- some vaginal hysterectomy specimens. The tional bleeding. The aim of the procedure is uterus is first probed and then opened either to remove superficial and basal endometrium, anteriorly with incisions into the cornua or leaving a base of so that men- bisected laterally. Opening the uterus anteri- strual bleeding is controlled or abolished. orly is the more cautious approach and if this Endometrial resection specimens appear as incision is used, care is required to expose multiple chunks of firm yellow and soft pink fully the cornua. Uteri containing cancers tissue, representing myometrium and should be either pinned out on a cork board endometrium. As with curettings, all the tis- or have cotton wool gently stuffed into the sue should be embedded. Diathermy artefact cornua before being placed in fixative. may interfere with the reporting of these Opening the uterus laterally is quicker and specimens, particularly as it tends to be most the uterus opened in this manner can be severe in superficial endometrium. placed directly into formalin, without further Gross examination ofuterine specimens 391

attention. But unless care is taken during Endometrial polyps can be smooth surfaced bisection, the knife may slip out of the plane or papillary, sessile or pedunculated, soft or of the uterine cavity. firm. Endometrial carcinoma sometimes

begins in a polyp, and all polyps should be J Clin Pathol: first published as 10.1136/jcp.46.5.388 on 1 May 1993. Downloaded from NO MACROSCOPIC ABNORMALITY submitted in their entirety for histological It is recommended that the following blocks examination. should be taken from a uterus with no macro- scopic abnormality: two blocks of the full CERVICAL INTRAEPITHELIAL NEOPLASIA, PAST thickness of the cervix, including the squamo- OR PRESENT columnar junction (anterior cervix and In hysterectomy specimens of patients with a posterior cervix) and a variable number of history of dyskaryotic smears or a current blocks of full thickness of the corpus, usually diagnosis of CIN, the cervix should be ampu- two to four, depending on the length of the tated and all submitted. The amputated uterus; isthmus; body endometrium; and fun- cervix can be treated exactly like a cone biop- dus endometrium (fig 2). All the blocks sy specimen, but its larger size means more should be full thickness through the blocks will have to be taken. In cases of a his- myometrium. If vaginal tissue is attached, it tory of CIN the yield of a positive diagnosis is should be sampled. If the tubes and low and a modification can be used to save are attached, each structure should be sec- time. In these cases the ectocervical resection tioned. The ovaries should be bisected in line may be blocked tangentially before the their broadest plane passing through the remainder is sliced parasagittally (fig 3). hilum. When reporting, this modification will permit concentration on the squamocolumnar junc- BENIGN CONDMIIONS tion and ectocervical resection line. If there are multiple leiomyomata in the uterus at least three of these should be sam- CERVICAL CANCER pled. If there is one large leiomyoma at least The usual surgical procedure for a cervical two blocks should be taken. Blocks of leiomy- cancer is a radical hysterectomy and lymph omata should always include the interface node dissection. In young women the adnex- with myometrium as invasion of the ae are often spared. A radical hysterectomy myometrium is a helpful feature of malignan- includes a vaginal cuff several centimetres cy. Any soft, necrotic, or haemorrhagic tissue wide, broad strips of parametria, and a vari- should be submitted. Adenomyosis appears able proportion of the broad, round, and as whorling and thickening of the myometri- uterosacral . um. Occasionally, small blue spots represent- The size, site, growth type, depth, com- ing endometrium, are seen. Adenomyosis pleteness of excision should be noted about a

usually hugs the endometrial-myometrial bor- cervical tumour. http://jcp.bmj.com/ der and extends for a variable distance into Size: Measure in three dimensions and the myometrium. By contrast, an adenomy- include the dimensions of the os. oma may be seen anywhere in the myometri- Site: Large tumours are often circumferential. um without any relation to the endometrium. Smaller ones preferentially affect the anterior or posterior lips. Figure 2 Routine Growth: The tumour may be fungating, infil- blocking ofthe uterus (AC: trating, ulcerated or polypoid, or show a mix- on September 28, 2021 by guest. Protected copyright. Anterior cervix; PC: ture of these characteristics. and Posteior cervix; E1-E3: Endometrium; FIB: haemorrhage should be noted. Fibroid; POL: Polyp). Depth: Recorded as depth of tumour infiltra- tion or total cervical wall thickness. Disease of the parametria: Macroscopic disease of the parametria is best assessed by slicing the cervix horizontally through 3 o'clock and 9 o'clock. Look for tumour extending

Figure 3 Blocking ofthe cervix in a hysterectomy specimen in cases ofhistory ofCIN. (AC: Anterior cervix: PC: Posterior cervix; RC: Right cervix; LC: Left cervix.) 392 Scuny, Patel, Wells

through the full thickness of the cervical wall tumour and the resection lines can be to reach parametrial fat. obtained in oversized blocks, which are hand- Disease of vagina: Early disease can be diffi- processed and cut on a sledge microtome.

cult to assess as the fornices are often not Unfortunately, this excellent technique is out J Clin Pathol: first published as 10.1136/jcp.46.5.388 on 1 May 1993. Downloaded from apparent in the resected specimen. of favour in many pathology departments Disease of the body of the uterus: Although cor- because it requires special equipment and is pus disease does not change the stage of a so time consuming. The remainder of the cervical cancer, it does worsen prognosis. should be sampled by parallel In a radical hysterectomy and lym- slices, beginning closest to the cervix and pay- phadenectomy specimen it is difficult to avoid ing particular attention to sample any thick- taking numerous blocks. Where possible, ening or induration. Small lymph nodes may economy should be exercised. The circumfer- be identified in the parametrium. The ence of the vaginal resection line can be remainder of the uterus and, if present, the blocked in strips in one or two cassettes. Note adnexae should be sampled according to the that sometimes in advanced tumours the "benign conditions" protocol. In cases of ade- vagina may be affected by tumour in submu- nocarcinoma of the cervix, particularly ade- cosal lymphatic channels, while the mucosa noma malignum, attention should be paid to remains normal. With a macroscopic tumour, the ovaries as there is an association with as a minimum, the tumour should be sam- mucinous tumours of the ovary. pled by a full thickness block from each of the The number of lymph nodes affected by four quadrants. If a tumour is longer than a metastases and their location is of crucial cassette then four additional blocks from the importance to the clinician and determines upper endocervix or isthmus should be whether postoperative radiotherapy will be added. The remainder of the cervix is then given. Lymph nodes from cases of cervical carefully longitudinally sliced, looking for cancer will arrive in the laboratory in labelled more deeply invasive tumour. The anterior pots. It is helpful to arrange and number the and posterior blocks can be used to assess the pots in a logical order, with right and left next anterior (bladder) and posterior resection to each other (fig 4). All lymph node tissue lines, which can be inked. The blocks from should be embedded. The only exception to the right and left sides of the cervix are used this rule is when a large node shows obvious for assessment of the degree of disease in the tumour in which case sampling will suffice. It parametrium, and these two blocks should is permissible to put more than one lymph include some inner parametrium. It is usually node in each cassette, but it is counterpro- not worth inking the parametrial resection ductive to stuff the cassette with fatty tissue, lines if the parametria include a thick cuff of which will inevitably process poorly. If a normal looking fat. In some specialist centres lymph node has been sliced, then all pieces

the entire cervix is blocked in cases of cervical should be placed into one cassette if possible. http://jcp.bmj.com/ cancer. If a tumour cannot be found macro- A large node may require two or more cas- scopically, then this is mandatory. In large settes. The number of lymph nodes embed- cervical tumours a good overview of the ded in each cassette should be recorded. A single deep level, as well as the standard sec- tion cut from each lymph node block, will increase the yield of metastases.

Figure 4 Guide to Univenity of Loodo Depsmae of Paoholo on September 28, 2021 by guest. Protected copyright. blocking lymphadenectomy specimens in utenrne LYMPHADENECTOMY RECORD ENDOMETRIAL CANCER cancers. A protocol for the histopathological reporting of endometrial carcinoma is shown in fig 5. The location, size, growth pattern, and extent of myometrial and cervical disease should be recorded from macroscopic examination of an endometrial carcinoma. Location: The tumour may be from the fun- dus, body, isthmus, cornu, and be from the right or left side, anterior or posterior. Size: Measure in three dimensions in cen- timetres. Growth pattern: The tumour may be solid or papillary or a mixture of these patterns, and may be ulcerated, necrotic, or haemorrhagic. Myometnial invasion: To assess the deepest point of myometrial invasion the uterus should be cut in parallel slices, virtually full thickness, but with the serosa intact, so that the uterus is still hanging together. Measure maximum depth of myometrial invasion, the overall thickness of the myometrium, and the minimum distance of the tumour from the serosal surface in millimetres. Cervical spread: Cervical disease changes the stage of corpus cancer. Direct spread is easily Gross examination ofuterine specimens 393

seen, but metastases to the endocervix are University of Leeds Depament of Pathology also quite common. These can be deceptively small and innocent looking and may appear Protocol for the Pathological Reporting of

as small, congested, or haemorrhagic polyps. J Clin Pathol: first published as 10.1136/jcp.46.5.388 on 1 May 1993. Downloaded from Endometrial Adenocarcinoma Blocks of the tumour should be full thick- ness through the uterus so that the depth of UTERUS: Weight. ... - g (without appendages) TUMOUR: myometrial invasion can be assessed histolog- Dimensions: ...... Soid ically. Blocks should be labelled to indicate where they are taken from. If the myometri- UIerated Tumour size: ...... cm. Necrotic um is too thick for a single cassette, use two Is the endocervix involved by tumour? [YES|N H.asmntai cassettes with appropriate designation. Apart from sampling of the tumour, block taking Is there myometrial invasion? [Y NO from a uterus with an endometrial cancer should follow the routine outlined above. <1'31 1I11 * 1 Lymph nodes should be handled in the same way as Overall dtickness of myometiiun cm cervical carcinoma.

Depth of invasion ...... cm Minimum distace of tumour from serosal surface cm PELVIC EXENTERATION Pelvic exenterations may be of three types: total, anterior, or posterior. Total pelvic exen- teration includes the uterus and adnexae, bladder and distal ureters, anorectosigmoid colon and pelvic peritoneum. Anterior exen- teration excludes the anorectosigmoid; poste- rior exenteration excludes the bladder. Although performed in late stage disease, pelvic exenteration is used as a curative pro- cedure, not for palliation. Special considera- tion should be given to the various resection ADNEXA lines and invasion of the rectum or bladder by Nma Abnornal (specify) Lymph nodes (specify group and number tumour. Right ovary Left ovary 1 Mor-Yosef S, Lopes A, Pearson S, Monaghan JM. Right tube Instruments and methods: Loop diathermy cone biopsy. Left tube Obstet Gynecol 1990;75:884-6. 2 Robboy SJ, Kraus FT, Kurman RJ. Gross description, processing and reporting of gynecologic and obstetric COMMENTS specimens. In: Ferenczy A, ed. Blaustein's pathology of the female genital tract. Third edn. New York: Springer http://jcp.bmj.com/ Figure 5 Protocolfor the pathological reporting ofendometrial adenocarcinoma. Verlag 1987:925-40. on September 28, 2021 by guest. Protected copyright.