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Abstract
Pathological examination of surgical specimens and compilation of a surgical pathology report comprises a series of events which includes macroscopic examination and tissue sampling, either complete or selected. This step is critical but often overlooked in the literature and not given the attention it deserves. In this review, we discuss the macroscopic examination and grossing of gynaecological pathology specimens, with reference to national and international protocols. We provide guidance as to the degree of sampling necessary in different scenarios and stress that a common-sense approach is necessary with flexibility in the degree of sampling depending on a variety of factors.
- Pathology, Surgical
- UTERUS
- OVARY
- PLACENTA
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Introduction
Pathological examination of surgical specimens starts with the macroscopic examination and sampling (either complete or selected) of the specimen, followed by histological examination, sometimes combined with ancillary studies such as immunohistochemistry and molecular testing. While most of the published literature understandably focuses on morphological features and ancillary studies, careful macroscopic examination and grossing is as important. In this review, we focus on the macroscopic examination of gynaecological pathology specimens especially, but not exclusively, concentrating on neoplasms. When available, we refer to national and/or international guidelines and recommendations. We also provide our experience based on local practices. General issues regarding macroscopic examination of pathology specimens are covered in another review in this issue.1
Macroscopic examination and sampling of omentum
An important cornerstone of omental examination is complete slicing at thin 5 mm intervals with careful macroscopic examination and palpation to determine if any nodules are present. Most national and international protocols suggest the submission of four to six blocks from omental resections performed as part of staging for known or possible gynaecological neoplasms. For example, the International Collaboration on Cancer Reporting (ICCR) data set for reporting of carcinomas and borderline tumours of the ovaries, fallopian tubes and peritoneum recommend four to six blocks of a grossly normal omentum in patients with an ovarian carcinoma or a borderline tumour2 as does the United Kingdom Royal College of Pathologists (RCPath) data set for histopathological reporting of carcinomas and borderline tumours of the ovaries, fallopian tubes and peritoneum3 and the structured reporting protocol of the Royal College of Pathologists of Australasia (RCPA) for carcinomas of the ovary, fallopian tube and peritoneum.4 The College of American Pathologists (CAP) Protocol for the Examination of Specimens From Patients With Primary Tumors of the Ovary, Fallopian Tube, or Peritoneum recommends 5–10 blocks of a grossly negative omentum in a patient with an ovarian serous borderline tumour, serous carcinoma or immature teratoma but makes no recommendation for other ovarian neoplasms.5 When dealing with an ovarian neoplasm, sampling of three to five blocks is recommended in one study6 and another suggests at least one block for every 20 mm of maximum omental dimension.7 The ICCR, CAP and RCPA data sets recommend that in patients with tubo-ovarian high-grade serous carcinoma (HGSC) who have received neoadjuvant chemotherapy, four to six blocks of omentum should be examined to assess tumour response to therapy (chemotherapy response score).8 9
With regard to patients with endometrial carcinoma where an omentectomy is performed for staging purposes, the RCPath data set states that one block, taken from an area of obvious tumour, is adequate in cases where macroscopically visible tumour nodules are present. No recommendations regarding the degree of omental sampling in endometrial carcinomas are provided in the ICCR, RCPA or CAP data sets.
In resource-limited settings, we suggest that the degree of omental sampling should be dependent on the pathology of the primary neoplasm, in the ovary or elsewhere. For instance, if the ovary is clearly benign on gross examination (and following histological examination), one block from a macroscopically normal omentum is sufficient. If histological examination reveals a malignant or borderline tumour, omental sampling should be increased to four to six blocks. Similarly, if there is obvious gross tumour involvement of the omentum, only one to two blocks are needed to confirm the presence of metastatic disease. In cases of endometrial carcinoma, if the omentum is macroscopically normal, we recommend submission of two to five blocks depending on the carcinoma type (with high-grade carcinomas requiring more generous omental sampling).
Following histological examination, the number of blocks could be increased, for example if a HGSC, clear cell carcinoma, high-grade endometrioid carcinoma, low-grade serous carcinomas (LGSC) or serous borderline tumour, especially of micropapillary type, is present within the ovary or tube, since there is a higher incidence of extra-adnexal disease with these neoplasms, which may not be visible grossly. Conversely, if the ovary contains a mucinous tumour or a low-grade endometrioid carcinoma, additional sampling is not necessary given the low incidence of metastatic disease. It is stressed that a common-sense approach should be used and there is always the option of going back and submitting more blocks for histological examination once the pathological findings of the primary neoplasm are elucidated.
Macroscopic examination and sampling of tubo-ovarian masses
Most protocols recommend sampling one block per cm of an ovarian neoplasm or two blocks per cm of an ovarian mucinous neoplasm greater than 10 cm in maximum dimension.2–5 However, the degree of sampling can be tailored depending not only on the macroscopic appearance but also the histological tumour type. Sometimes intraoperative frozen section indicates the tumour type, which in turn can guide the degree of sampling; in cases not evaluated intraoperatively, additional sampling can be performed later, after examination of routine sections. With all ovarian neoplasms, careful inspection of the capsular surface is necessary to look for foci of surface rupture, defects, adhesions or tumour deposits, all of which may affect tumour staging and management. If an ovarian mass is opened and/or sliced to aid fixation, the tumour dimensions and aforementioned features should be documented beforehand since they may be much more difficult to assess following opening and/or slicing of the specimen.
With a thin-walled ovarian cyst with a smooth external surface and no solid, nodular or papillary areas, only limited sampling is generally necessary, even if the cyst is large. Conversely when solid, nodular or papillary areas are present on the internal or external surface, the tumour should be sampled at the standard rates suggested above. With a uniformly solid white/yellow neoplasm without gross areas of haemorrhage or necrosis, the differential diagnosis is likely benign (fibroma, thecoma or benign Brenner tumour) and only limited sampling is necessary. In neoplasms with a heterogenous gross appearance, with solid and cystic areas or with foci of haemorrhage and/or necrosis, the features should be described and sampling of the macroscopically different areas should be undertaken. Blocks should be taken from areas of surface rupture, defects, adhesions or tumour deposits.
HGSCs and clear cell carcinomas of the tube/ovary are typically uniformly malignant throughout, although different architectural patterns may be present in different areas. As such, these neoplasms generally require more limited sampling than with other morphological tumour types. In contrast, mucinous neoplasms in particular (the presence of a mucinous neoplasm can typically be suspected from the gross appearances) require extensive sampling, especially concentrating on solid and necrotic areas. This is because of the propensity of primary ovarian mucinous neoplasms to be composed of an admixture of benign, borderline and malignant areas.3 4 10–12 The malignant component may also exhibit different patterns of invasion (expansile or infiltrative) and malignant mural nodules may be present; these features, when present, may influence patient management and prognosis. Similarly, extensive sampling and knowledge of the distribution of disease helps to distinguish between primary and secondary ovarian mucinous neoplasms, the latter often being bilateral with surface disease and exhibiting a nodular pattern of ovarian involvement and extraovarian spread. It has been recommended that ovarian mucinous neoplasms should initially have one block per cm from tumours <10 cm and two blocks per cm from tumours >10 cm.3–5 10–12 However, for thin-walled unilocular or multilocular tumours in which the cysts have a uniformly smooth lining, less extensive sampling is required. If initial sections show a mucinous borderline tumour with worrisome features, such as intraepithelial carcinoma, microinvasion or microinvasive carcinoma, additional sampling is recommended.
Endometrioid and low-grade serous neoplasms (serous borderline tumour and LGSC) also should be extensively sampled. Primary ovarian endometrioid carcinomas often exhibit areas of different morphological grades within the same neoplasm and, although grading should be performed taking into consideration the entire tumour, extensive sampling helps in this regard and may also detect areas of undifferentiated carcinoma (dedifferentiated carcinoma). Moreover, within a benign or borderline endometrioid neoplasm, extensive sampling may assist in identifying small foci of carcinoma. Extensive sampling of ovarian serous borderline tumours, especially of micropapillary type, is indicated to identify small foci of overtly invasive LGSC.
Sampling of fallopian tube, including appropriate sampling to determine site of origin of extrauterine HGSC
It is now well established that a significant majority of extrauterine HGSCs arise from the distal fimbrial end of the fallopian tube from a precursor lesion known as STIC (serous tubal intraepithelial carcinoma).13–16 Criteria for site assignment in extrauterine HGSC have been proposed and adopted by the ICCR and the 2020 WHO Blue Book.13–16 Use of these criteria results in a high proportion (approximately 80%) of extrauterine HGSCs being classified as tubal in origin while primary peritoneal HGSCs are exceedingly rare; this diagnosis should only be made when there is no ovarian parenchymal HGSC and no mucosal STIC or HGSC within either tube, both of which should be visualised in their entirety and examined in total histologically using a Sectioning and Extensively Examining the FIMbriated end (SEE-FIM) protocol (figure 1).17 A SEE-FIM protocol for examining the fallopian tubes is only necessary in extrauterine HGSCs with two grossly normal fallopian tubes, including fimbrial ends. If one or both fallopian tubes is entirely or partially embedded in a mass, the HGSC is regarded as being of tubal origin.
Sectioning and Extensively Examining the FIMbriated end (SEE-FIM) method for sampling fallopian tube. The fimbrial end of the tube is amputated and sliced thinly at 1 mm intervals longitudinally in the sagittal plane; the remainder of the tube is sectioned transversly at 1 mm intervals and the entire tube is submitted for histological examination.
In other scenarios, including when dealing with other tumour types (adnexal or other) and benign cases, examination of the entire tube(s) using a SEE-FIM protocol is not necessary, although this is performed in some institutions. In these cases, documentation of the presence or absence of the fimbrial ends is needed, followed by entire submission of the fimbrial ends and representative transverse sections of the non-fimbrial tube; the exception to this is risk-reducing surgeries (see next section).
Recommendations for pathological sampling of prophylactic/risk-reducing gynaecological specimens
The most common prophylactic gynaecological specimens comprise risk-reducing bilateral salpingo-oophorectomies in patients with a known hereditary predisposition to tubo-ovarian carcinoma, such as those having BRCA1 or BRCA2 germline pathogenic variants (PVs) or occasionally germline PVs in other genes known to confer a hereditary predisposition such as BRIP1, PALB2, RAD51C and RAD51D. Occasionally, risk-reducing surgery is undertaken in patients with a family history of tubo-ovarian carcinoma or family history of breast carcinoma, but with no identifiable genetic predisposition or who are awaiting genetic testing. In such cases, the ovaries and fallopian tubes should be submitted in total for histological examination and the tubes should be blocked using a SEE-FIM protocol. This approach has been recommended by the ICCR and organisations such as RCPath, CAP and RCPA. Peritoneal washings should also be submitted by the surgeon in such cases. A related scenario is patients with breast cancer undergoing salpingo-oophorectomy as part of their oncological treatment (hormonal ablation). Many practices apply the SEE-FIM protocol to these instances.
Prophylactic hysterectomy, typically with bilateral salpingo-oophorectomy, is increasingly being undertaken in patients with known Lynch syndrome (LS) given the increased risk of endometrial and ovarian carcinoma. A limited number of studies have examined the pathological findings in such cases and have identified a significant incidence of occult endometrial carcinoma or hyperplasia.18–20 For example, in one study of 25 cases, there was a 32% detection rate for endometrial carcinoma or a precursor lesion.18 In another study, there was endometrial hyperplasia in 5 of 29 (17%) cases.19 In a third study, abnormal histological findings were identified in 9 of 39 (23.1%) cases, comprising three endometrioid carcinomas, four atypical hyperplasias and six hyperplasias without atypia.20 Given these findings, it has been recommended that endometrial sampling should always be undertaken prior to prophylactic surgery in patients with LS since identification of an occult endometrial cancer may influence the preoperative workup, intraoperative assessment or surgical procedure. It is also recommended that in such specimens, the endometrium, including the lower uterine segment (endometrial carcinomas in patients with LS may involve the lower uterine segment), should be submitted in total for histological examination.18–20 It has been further recommended that the ovaries and fallopian tubes should be examined in total using a SEE-FIM protocol. As far as we are aware, there are no national or international recommendations, but we endorse total submission of the endometrium, tubes and ovaries in such cases.
Macroscopic examination and sampling of hysterectomy and other uterine specimens
The reader is referred to the guidelines issued by the International Society of Gynecological Pathologists (ISGyP) Endometrial Carcinoma Project, on which this section is largely based.21 The resource is freely available (doi: 10.1097/PGP.0000000000000552) and provides guidance on many of the issues discussed herein. While primarily dedicated to specimens obtained in the setting of endometrial cancer, recommendations on other pertinent aspects can also be found in this resource.
Intact hysterectomy specimens
Preparation
Knowing the indication for the surgical procedure is the first step in the macroscopic examination of any hysterectomy specimen. The preoperative impression (clinical and radiology) and/or preoperative biopsy diagnosis are important in dictating the sections that will be submitted initially for histological examination. These factors will also direct the gross examination and in certain instances prompt documentation of margin status.
Orientation
Whenever possible, the specimen should be orientated as it allows for more accurate description of the macroscopic findings and labelling of sections submitted, which can be useful if the specimen needs to be examined again after initial processing or when additional sections of a particular area are needed. Orientation of the specimen is achieved by locating the anatomical landmarks of the anterior and posterior aspects of the uterus: the anterior wall is typically concave and has a shorter peritoneal reflection compared with the posterior wall, which has a convex outline when the uterus is seen in a sagittal plane (figure 2). If the adnexa are present and attached to the uterus, its visualisation from above (on the transverse plane) can be helpful: the fallopian tube typically curves around the ovary, with the former facing the anterior and the latter facing the posterior aspect of the specimen.
The anterior aspect of the uterus (A) has a peritoneal reflection with a flat, horizontal edge compared with the pointed edge of the serosa in the posterior aspect of the uterus (B). The posterior serosa also has greater distal extension (blue arrow) leading to a narrow paracervical soft tissue roughened surface; in contrast, the anterior paracervical soft tissue roughened surface is wider (yellow asterisk).
Specimen weight and measurements
Recording the weight of the uterus is necessary in the USA for billing purposes: the Current Procedural Terminology has different codes for reimbursement assigned to uteri ≤250 g and >250 g.21 Other than this, the weight has no clearly defined diagnostic or prognostic role. Similarly, recording of specimen measurements varies among practices. Detailed protocols mandate recording three dimensions of the uterus (anterior to posterior, superior to inferior and right to left). Since recording three dimensions has no utility beyond documentation for epidemiological or quality assurance purposes, a simplified approach would be to record only the largest specimen dimension. This may be preferred if time or staffing constraints require a more expedited examination. Obtaining weight and dimension measurements is best done at the time of initial examination before opening and sectioning. Measuring after fixation is less desirable, as formalin fixation is known to reduce size and weight of tissues.22 23
Margin assessment
Reporting the status of surgical margins is required in the setting of uterine corpus malignancies involving the cervix (endometrial carcinoma or uterine sarcoma). As this is unknown at the time of initial specimen examination, routine inking of the surgical margins in a hysterectomy specimen performed for known or suspected uterine corpus malignancy is recommended; some recommend this even when the hysterectomy has been performed for benign conditions given the small chance of finding a malignancy but this is not widespread practice. The margins in this case are (1) The ectocervical mucosal margin, comprising the outer edge of ectocervical mucosa, and (2) The cervical/paracervical soft tissue margin, defined as the rough surfaces around the outer circumference of the cervix spanning between the uterine serosa and the ectocervical mucosal margin (figure 3). Hysterectomies for endometrial carcinoma with suspected or known cervical involvement preoperatively are often radical, meaning they include bilateral parametrial soft tissues (which are considered true surgical margins) and the vaginal cuff (which becomes the mucosal margin). These margins should be inked and distance to the tumour or suspicious lesion should be recorded. Inking should be performed prior to opening (see section on hysterectomies performed for cervical cancer).
The paracervical soft tissue roughened surface should be treated as a margin and always inked in both anterior (A) and posterior (B) aspects (yellow asterisk marks the inked margins). The distal mucosal margin (C) corresponds to the outer edge of the ectocervical mucosa (pink arrowheads). Radical hysterectomy specimens have bilateral parametrial soft tissues (D, parametrial tissues indicated by blue arrows), which should be inked.
Inspection of the serosal surface
The uterine serosa is normally smooth and shiny. The presence of any abnormalities, such as tumour involved, haemorrhage, adhesions or nodules, should be noted.
Opening the uterine cavity
This step should be performed as soon as the specimen is received in the pathology laboratory in order to reduce cold-ischaemic time and guarantee appropriate tissue fixation. We acknowledge that this step is not always performed since it requires prompt access to surgical pathology resources; nonetheless, it should be attempted at least in cases with a confirmed or suspected diagnosis of malignancy. This step is performed after weighing, measuring and inking, by cutting the right and left sides of the wall. Scissors should be used, cutting each side by carefully inserting the scissors. Cutting at regular intervals will gradually expose the cavity, which in turn will guide the cutting process: for instance, if the lesion is found to be on the plane of cutting, the prosector can choose to go around it to keep it intact and maintain its connection to the wall (figure 4). We advise against inserting a blade blindly into the cavity; we also strongly advise against inserting surgical forceps (tweezers) blindly into the cavity to guide the blade. These approaches may result in tumour fragmentation and/or dislodgement.
The uterine cavity should be opened on both right and left sides with a scissor (A). Careful cutting will gradually expose the cavity, and further cutting should avoid transecting masses at their base (B, which shows the base of the polypoid tumour in the plane of scissor cutting, indicated by blue arrow).
Inspection of the endometrial and cervical mucosal surfaces
The surface of both the endometrial and endocervical mucosae is normally flat to slightly ragged. Any deviations from this should be recorded; these most commonly comprise discrete lesions such as polyps or masses, but also variations in thickness, discolouration, ulceration and fibrosis. The location and appearance of each lesion should be documented. In terms of size, at least the largest measurement should be recorded. In the setting of endometrial carcinoma, there is evidence that maximum tumour dimension correlates with risk of recurrence and advanced stage.24–26 In the setting of uterine sarcoma, maximum tumour size is a staging criterion;27 it is also a factor used for risk stratification of several mesenchymal neoplasms including smooth muscle tumours,28 perivascular epithelioid cell tumour29 and inflammatory myofibroblastic tumours.30
Sectioning
This is the last step prior to tissue fixation. It involves cutting the uterine wall at regular intervals, between 5 mm and 10 mm, to facilitate exposure of the tissue to the fixative. Sectioning of the uterine corpus is performed serially from fundus to lower uterine segment; each section should be done in the transversal plane, parallel to the anteroposterior dimension. Sectioning of the cervical wall is performed in the longitudinal plane, parallel to the cervical canal, initially at the midline and serially towards the lateral aspects of the cervix. Sectioning of the uterine corpus and cervix should start on the mucosal side and go through most but not all the wall thickness, leaving 3–5 mm of the outer wall attached to maintain the specimen together (figure 5). Subserosal or serosal lesions should also be sectioned at 5–10 mm intervals, but again leaving them attached to the uterus whenever feasible.
Standard sectioning of the uterine corpus includes serial transverse sections from the proximal (fundus) to the distal (lower uterine segment) corpus.
Inspection of the cut surfaces
Lesions not noted on inspection of the serosa and mucosal surfaces should become evident after sectioning. Each lesion should be carefully inspected for features suspicious for malignancy. These include: irregular, indented or frankly infiltrative border; satellite lesions, close or adjacent to the main tumour but discontinuous or within vascular spaces; heterogeneous (in terms of colour and consistency) or soft cut surface, depressible to the touch; haemorrhage; and necrosis. These features will separate lesions concerning for malignancy from the more common uterine leiomyoma, which has smooth borders, a bulging cut surface with a firm white homogeneous appearance and uniform rubbery consistency. Importantly, leiomyomas can have degenerative changes which often impart a different gross appearance. Description of such changes is beyond the scope of this review, and the reader is referred to reference books. In essence, lesions falling within the spectrum of typical leiomyoma can be described conservatively with documentation of the range of individual tumour largest dimensions and either a precise or approximate (if numerous) count of lesions. Every lesion with abnormal or suspicious features deserves individual description of size (largest dimension), location and appearance.
Fixation
Hysterectomy specimens should not be placed in fixative intact (meaning unopened). The specimen should be placed in fixative (most often buffered formalin at 10% concentration) as soon as possible but only after it has been opened and sectioned. Some practices suggest pinning the specimen on a flat surface prior to submersion in fixative. Paper towels can also be placed in between sectioned tissue to ensure the fixative will reach it. Fixation will not be optimal if the uterus ends up repositioned to its anatomical (closed) position once in the fixative container.
Tissue sections for histological examination
Specimen sampling is dictated by the preoperative diagnosis, the macroscopic findings and type of hysterectomy. Guidance on the sections required for submission is provided in the following paragraphs:
Hysterectomy specimens for benign conditions
Hysterectomy specimens performed for benign conditions such as uterine prolapse, adenomyosis, or unexplained abnormal uterine bleeding or pelvic pain, are treated in a standard fashion of two full-thickness sections from the cervix (one anterior and one posterior), and two full-thickness sections of the uterine corpus (one anterior and one posterior). Ideally, each tissue section should be placed in a different block to maintain location. Areas of macroscopic abnormality should be always included in the sections submitted for histological evaluation; they can be part of the standard sections listed above or extra sections. Any mass or polyp in the endometrial or endocervical mucosal surfaces should be sampled; the section(s) should include the interface with the surrounding/underlying normal tissue. If the lesion is 2 cm or less in size, it is recommended that it is submitted entirely. Lesions larger than 2 cm can be sampled at a rate of one section per cm of greatest dimension. If the cervix is not removed (subtotal hysterectomy), the lower limit of the specimen should be sampled either via longitudinal sections, including the lower uterine segment, or via a transverse section.
Sampling of hysterectomy specimens with leiomyomata (fibroids) should include, in addition to the standard sections above, additional sections of the nodules. In terms of sampling, there is wide variation in practices. For example, at Brigham and Women’s Hospital (Boston, USA), grossly benign lesions (leiomyomata) with a typical appearance are sampled in up to four tissue blocks, with one to two sections in each block.31 At Sunnybrook Health Sciences Centre (Toronto, Canada), two blocks from the tumours are obtained per each 5 cm of the specimen greatest dimension: for instance, if the uterus with masses measures 8 cm in greatest dimension, two blocks are submitted; if size is 17 cm, four blocks are submitted.32 The degree of sampling can be limited if the macroscopic appearances are typical of benign leiomyomas (see above) and it is stressed that careful gross examination is paramount. The RCPath Tissue Pathways for Gynaecological Pathology states that ‘when fibroids appear typical on gross examination, minimal sampling, usually 1 block of the largest fibroid and 1 or 2 others selected at random, will suffice.3 More extensive sampling is required if clinical information is provided that suggests unusually rapid growth or abnormal radiological appearances, particularly in postmenopausal status. The presence of softening, haemorrhage, cystic degeneration or variation in colour should prompt more extensive sampling. The junction with myometrium should be sampled.’
Hysterectomy specimens for endometrial carcinoma and endometrial precursor lesions
In addition to standard sections, two full-thickness sections of the lower uterine segment (one anterior and one posterior) should be submitted. These sections are helpful in picking up primary lesions (see section on prophylactic/risk-reducing specimens above) and also in identifying extension of the endometrial neoplasm to the lower uterine segment and the cervix (which has staging implications). To this end, if an endometrial tumour is grossly involving the lower uterine segment and/or cervix, an alternative approach to sectioning is to include one or two longitudinal composite sections in serial blocks that span the distal cervix, endocervix, lower uterine segment and fundus (instead of the traditional sections taken separately from the uterine corpus and lower uterine segment). A continuous longitudinal section will allow visualisation of any tumour spread into the lower uterine segment and cervical wall.
As with any discrete lesion, sampling of the endometrial tumour should be undertaken at a rate of one section per cm of greatest tumour dimension (and submission of the entire tumour if it is 2 cm or less). Sampling should always include at least one full-thickness section (from endometrium to serosa) chosen at the point where the deepest invasion into the myometrium is visualised.
If no lesion is grossly identified in a case with a preoperative biopsy diagnosis of malignancy, the endometrium should be sampled entirely for histological examination. If the hysterectomy was performed for atypical hyperplasia/endometrioid intraepithelial neoplasia, submission of the entire endometrium should always be performed, unless there is obvious malignancy noted macroscopically in which case selected sampling as above can be undertaken. With a preoperative diagnosis of hyperplasia without atypia, we recommend submission of at least four blocks unless an obvious endometrial tumour is seen grossly; in some institutions, the entire endometrium is submitted in such cases. In all of these scenarios, and if resources are an issue, once one composite full-thickness section from the cervix to uterine fundus (both anterior and posterior) is taken, the remaining endometrium can be submitted with only a small amount of attached underlying myometrium, permitting several sections to be placed in a single cassette. The site of origin of these sections (anterior/posterior, left/right) should be added to the block key in case significant pathology is identified and sectioning of the remaining myometrium is required.
Sampling of radical hysterectomies performed for endometrial carcinoma should include, in addition to the above, submission of the entire parametria on both sides. The parametria can be submitted attached to the wall or detached and serially sectioned. If present, the vaginal cuff should also be sampled, either en face or included in the sections from the cervix.
Hysterectomy specimens for suspected uterine sarcoma
In addition to standard sections (see hysterectomy for benign reasons above), any suspicious uterine lesion should be sampled at a rate of one section per cm of greatest tumour dimension. Sections should target areas of heterogeneity (interface between soft and rubbery areas, interface between necrotic and viable tissue, interface between haemorrhagic and non-haemorrhagic tumour), as well as the interface between tumour and adjacent structures (endometrium, myometrium, parametria, endocervix, ectocervix).
Fragmented and partial uterine resection specimens
Many practices perform hysterectomy via laparoscopy, which depending on specimen size, may require fragmentation (morcellation) of the specimen inside a bag prior to removal via abdominal incision. Description of the uterus in these specimens is simplified as it only requires weighing and measuring the dimensions of the aggregate tissue. Careful examination and review of the operative note/specimen request form are important to identify all structures that should be present in the specimen. Each structure (cervix, endometrial surface, serosal surface, fallopian tubes, ovaries) should be stated as present or absent. Further examination and sampling are similar to intact hysterectomy specimens. However, there are often limitations depending on what anatomical structures can be identified; for instance, the serosal surface may not always be apparent, and obtaining full-thickness sections of the endometrium/myometrium may not be possible.
Partial resection specimens, namely myomectomy, are performed to remove a single lesion either via hysteroscopy or laparoscopy. If the specimen is intact, it should be measured in three dimensions and the external surface should be inked to determine margin status. If the specimen is fragmented, aggregate measurements are provided, and inking is not necessary. Macroscopic evaluation includes description of the tumour appearance and relationship to any normal structure present (endometrium, myometrium, serosa). Sampling reflects recommendations provided for intact hysterectomy specimens, whether the tumour appears benign or has suspicious features for sarcoma (see corresponding sections above).
Macroscopic examination and sampling of cervical specimens
Pathologists encounter a broad range of cervical specimens, ranging from small biopsies to loop excisions, encompassing loop electrosurgical excision procedure (LEEP), large loop excision of the transformation zone (LLETZ) and cold-knife conisation. Larger surgical specimens include trachelectomy and simple and radical hysterectomy which are performed for cervical cancers. Pelvic exenteration (PE) may also be performed for advanced or recurrent cervical cancer. The specimen type must be recorded in the macroscopic description and it is important to document the structures removed, to highlight cases where the tissue received is incomplete or includes more anatomical structures than expected. The reader is referred to recent consensus guidelines published by the ISGyP33 regarding gross examination and processing of cervical specimens, which forms the basis of the recommendations herein. This resource is freely available online (doi: 10.1097/PGP.0000000000000745) and although these guidelines are specific to endocervical adenocarcinoma, the same principles apply to squamous cell carcinoma.
Loop excision
The number of tissue pieces submitted and whether these comprise an intact loop or strips should be recorded, with each piece measured in three dimensions. For intact loops, this should include the diameter of the ectocervix in the 3–9 o’clock and 12–6 o’clock planes and the length of the specimen, corresponding to the length of the endocervical canal. For strips where no canal is recognised, each piece should be measured in three dimensions. The presence of orientating markers/sutures should be recorded; typically a clockface analogy is used with the suture placed at 12 o’clock or 3 o’clock, with the clockface orientated from the viewer’s perspective. If no orientation is provided, partial orientation is possible based on the shape of the external os, which is usually linear and aligned in the coronal plane. In a fragmented loop excision, mucosa can usually be recognised by its smooth, pale appearance while the deep stromal surface is roughened and cauterised. Inking of the resection surfaces varies among practices. If the specimen was removed using an electrosurgical device, the margins will be cauterised and therefore ink is not needed. In a cold-knife cone, however, inking is required for microscopic margin evaluation. If the specimen is orientated and comprises an intact loop, the stromal margin of the 12 o’clock and 6 o’clock halves can be inked in different colours; the same practice may be applied when the specimen can be orientated based on the appearance of the external os. The rationale for differential inking is to permit more accurate assessment of the extent and location of disease and margin involvement. In non-intact specimens, specimen inking is not required.33 If a ‘top hat’ specimen is received and if orientation is possible, the true endocervical margin may be inked.
If any macroscopic abnormality is identified, this should be described, measured and located anatomically if possible (see description and measurement of tumour below). The specimen is serially sliced at 3 mm intervals using the locally agreed-upon method (discussed below), and entirely submitted as sequential slices. Placing multiple slices in one cassette should be avoided. A block identification key annotating the origin of each piece of tissue in accordance with any orientating information should be provided.
Various methods for sectioning loop excisions exist. In some centres, intact loops are received fresh, opened in the midline anteriorly and pinned out for formalin fixation prior to serial sectioning parallel to the endocervical canal. If the loop is received in formalin, as is usual in most institutions, either parallel slicing in the sagittal plane or radial slicing may be performed. For parallel sliced specimens, each individual slice is placed in order in a separate cassette, with the cut surface nearest the endocervical canal face down. The radial method entails slicing the specimen perpendicular to the canal in a clockface fashion, producing wedge-shaped slices that are thicker at the stromal end; this requires trimming and submission of both the slice and excess trimmed portions. For fragmented specimens, these should be transversely sectioned perpendicular to the long axis. These specimens must be submitted entirely, the block designation clearly identifying their origin and relationship to one another.34
Trachelectomy
This procedure is performed for the management of small cervical cancers with the aim of preserving fertility; in such cases, the tumours are larger than those which can be managed by loop excision. A simple trachelectomy specimen comprises the ectocervix, endocervical canal, cervical wall and attached upper vaginal cuff; radical trachelectomy includes the lower parametria.35 The specimen should first be orientated according to any attached markers/sutures, designating anterior and posterior cervix and left and right parametria. The vaginal, endocervical and parametrial margins and outer surfaces of anterior and posterior cervical walls (these are not true surgical margins) should be inked. The area of the ectocervix in two dimensions, length of the endocervical canal, cervical wall thickness, minimal and maximal length of any attached vaginal mucosa and parametrial dimensions (medial to lateral) should be documented; parametria should not be stretched during measurement.34
As with loop excisions, various methods for sampling trachelectomy specimens exist. The ISGyP recommendations advocate opening the fresh specimen with a single cut parallel to the endocervical canal (ideally not through tumour) and pinning out, including the vaginal cuff, and then serially slicing parallel to the endocervical canal postfixation.33 The parametria are removed prior to fixation. For tissues received in formalin, an alternative is parallel slicing in the sagittal plane, as described for loop excisions. If no tumour is visible macroscopically (sometimes the entire tumour is removed by a prior loop excision) or the tumour is <2 cm in size, the entire specimen should be submitted; the rationale for this is that microscopic examination may alter the final tumour dimensions and stage. Each slice will incorporate the vaginal margin (if left attached, see below), endocervical margin and radial stromal margin. If the slices are too large to fit in a single cassette, they can be divided. Tumours larger than 2 cm can be representatively sampled, with a minimum of 1 block per cm of the greatest tumour dimension;34 the sections taken should be tailored to demonstrate the deepest point of invasion, the maximum longitudinal extent of the lesion and the closest distance to the endocervical, vaginal and stromal margins. Recommendations for sampling of the vagina, including the margin, vary. If there is a large attached vaginal cuff, this may be removed and handled separately. Perpendicular sections at the site where tumour lies nearest this margin are required at a minimum. The remaining circumferential vaginal resection margin may be blocked entirely as strips en face or, as representative perpendicular sections, depending on local preference.33 34 If the vaginal cuff is short and left intact, the vaginal margins can be sampled along with the cervix. Left and right parametria should be sliced and entirely submitted, noting the presence, size and number of any tumour deposits, lymph nodes or other lesions.
Hysterectomy
Radical hysterectomy is typically performed for cervical carcinomas and, as well as the uterine corpus and cervix, includes the upper vagina and parametria.36 Simple hysterectomy is sometimes performed for presumed small (typically stage IA) carcinomas. The ovaries and fallopian tubes may be removed depending on the clinical context; often the adnexa are not removed in premenopausal women.
The uterus should be weighed (depending on local practice). Other anatomical structures should be documented and measured; measurements for the cervix, vaginal cuff and parametria are as described above (see section on trachelectomy). In a radical hysterectomy for cervical neoplasia, the anterior and posterior cervical non-peritonealised stromal surfaces, vaginal margin and parametria should be inked.
In the context of a radical hysterectomy for a cervical neoplasm, if the parametrial tissues appear uninvolved by tumour, these are removed first, serially sliced and submitted entirely, maintaining laterality. If the parametria appear involved, they can be left intact and sliced in continuity with the cervix. A simple hysterectomy does not include surgically dissected parametria but if small fragments of parametrial soft tissue are present these should be submitted as a parametrial shave.34
If the specimen is received fresh, the cervix should be amputated and handled as per an unfixed trachelectomy with the uterine corpus opened and dealt with in the usual way. If the specimen is received in formalin, several methods for opening exist. One option is to amputate the cervix and serially slice either in the sagittal plane or radially, with the vaginal cuff remaining attached (figure 6). Another is to bivalve the entire uterine corpus and cervix and then submit the cervix as sequential radial slices. In terms of block selection from the amputated cervix, the approach is identical to that described above for trachelectomy specimens and varies depending on the presence or absence and size of any macroscopically evident tumour. The approach to sampling the vaginal cuff and parametria is also as described above. Sectioning of the lower uterine segment, uterine body and fundus should be performed in the setting of a cervical tumour to assess disease extent. At a minimum, sampling should include composite full-thickness blocks from the uterine isthmus to fundus anteriorly and posteriorly. If the cervix is amputated, a horizontal/transverse slice of the lower uterine segment immediately above the amputation point may be submitted, depending on local preference. The ovaries and fallopian tubes are sampled depending on local practice; in the case of radical hysterectomy for a cervical tumour, the ISGyP advocates serially slicing using a SEE-FIM protocol and, at a minimum, submitting the entire fimbriae together with representative sections from the non-fimbrial portion of tubes and ovaries.33 Any macroscopic lesions should be sampled.
This modified radical hysterectomy with left salpingo-oophorectomy and attached vaginal cuff, performed for cervical adenocarcinoma, has been inked in the fresh state, the cervix amputated and the uterus opened in the midline anteriorly (A–C). Extension of tumour into the uterine isthmus and lower body is visible macroscopically (C, arrow). Postfixation, the cervix is handled as per a trachelectomy and serially sliced in the sagittal plane, with the vaginal cuff left intact and attached to each slice of the cervix (D, vaginal cuff at arrow).
In cases of hysterectomy performed for a squamous intraepithelial lesion or other premalignant lesion, the entire cervix and any attached vaginal cuff should be submitted for histological examination using one of the methods described above.
Pelvic exenteration
PE is an en bloc resection of the uterus and vagina with or without vulvectomy and is further classified depending on the additional structures removed; anterior PE includes the bladder and urethra with or without ureters whereas posterior PE includes the rectosigmoid. Total PE includes both the lower urinary tract and rectosigmoid.37 This procedure is performed in some cases of locally advanced or recurrent pelvic malignancy, especially of cervical, vulval or vaginal origin.37
The structures present should be documented and measured and resection margins inked. Margins of interest include any cutaneous, vaginal, urethral, ureteric, intestinal, parametrial and other soft tissue margins. All structures should be opened to permit adequate fixation followed by specimen bisection in the sagittal plane through the tumour.38 Once bisected, both cut surfaces can be photographed and this may be annotated to record block selection.39 The tumour should be measured in three dimensions and its relationship to all structures and margins documented and any fistula formation noted. The principles of sectioning are as described previously, aiming to demonstrate the maximum tumour extent and relationship to structures such as the mucosa of the bladder, vagina and rectum; sections from these structures should be taken perpendicular to the mucosa in closest proximity to the tumour. Representative sections of all uninvolved organs should also be submitted. The margins of the vagina and parametria are submitted as described previously and remaining mucosal margins (urethral, ureteric, colonic, soft tissue) are taken as en face shaves unless there is nearby tumour, whereupon a perpendicular section is preferable.
Description and measurement of cervical tumours
If a tumour is identified on macroscopic examination, its appearance should be described and location documented relative to adjacent structures. The ectocervical versus endocervical location and position using a clockface or descriptive terms such as anterior, posterior, lateral, circumferential should be documented. The tumour extent should be documented, including extension into the vagina, parametria, lower uterine segment and uterine body. The tumour should be measured and at least the largest tumour dimension recorded. In some institutions, three dimensions are provided comprising the mucosal tumour area in two perpendicular planes and tumour thickness and/or depth of invasion, the latter measured from the cervical mucosal surface to the deepest point of invasion, also recording the cervical wall thickness at this point.33 Although only a single horizontal dimension is required by the ICCR,36 it is suggested that all three measurements are recorded at time of macroscopic assessment to assist with determination of final dimensions following microscopic examination. The tumour thickness and depth of invasion will be different if there is an exophytic or ulcerated tumour component. The macroscopic distance to relevant margins should be measured. In a loop excision this includes ectocervical and endocervical mucosal and stromal margins; the distance to vaginal and parametrial margins is also included in radical trachelectomy and hysterectomy specimens and in hysterectomies it is important to document macroscopic extension to the lower uterine segment or body. If the specimen is received fresh, it is recommended these measurements be taken before the specimen is opened, pinned out and fixed, to avoid overestimating tumour dimensions due to tissue distortion. It is also stressed that, although the gross measurements just described should be recorded, the final measurements on the pathology report should take into account both the gross and microscopic measurements.36
Macroscopic examination and sampling of vaginal specimens
Primary carcinomas of the vagina are rare and metastases are more common. Surgical excision of vaginal tumours is generally limited to small lesions confined to the vaginal mucosa.40 Specimens range from wide local excision (WLE) to partial or total vaginectomy; all excision types may form part of a radical hysterectomy or PE.40–42 In the absence of attached anatomical structures, these specimens are usually orientated by the surgeon. The components of the specimen and specimen dimensions (length, width, wall thickness) should be recorded and longitudinal and deep margins inked. Any visible tumour should be described, measured and the location noted as various tumour types show a predilection for different sites of origin. For example, squamous cell carcinomas are more common on the posterior wall while clear cell carcinomas are most commonly localised anteriorly, mesonephric carcinomas laterally and intestinal-type carcinomas inferiorly.43 44 The maximum horizontal extent (parallel to the mucosa) should be measured and the second horizontal dimension in a plane perpendicular to the first measurement may be provided but is not required.41 45 The depth of invasion should be estimated macroscopically. Relevant margins are the proximal and distal mucosal margins (upper and lower vagina) and the deep soft tissue margin which can be designated as anterior, posterior, right or left.42 Submitted sections should include tumour with the deepest point of invasion, interface with adjacent epithelium, resection margins and any abnormality remote from the tumour.
Macroscopic examination and sampling of vulval specimens
Vulval specimens include WLE, often performed for preneoplastic lesions or when malignancy is suspected but not yet proven, and partial or total radical vulvectomy, performed for biopsy-confirmed carcinoma. A WLE removes the vulval skin or mucosa but spares the subcutaneous fat and deep soft tissues.46 Radical vulvectomy removes tissue to the level of the deep fascia and may include the clitoris, labia majora and/or minora, portions of the vagina, urethra and/or anus.46 Typically these specimens are orientated by the surgeon and may be pinned to a cork board prior to fixation (figure 7). The cutaneous and deep stromal margins should be inked. Differential inking (using different colours for various margins) is useful, particularly if whole slices will fit in a single cassette.
This vulval wide local excision is received pinned to a cork board with orientating information provided by the surgeon.
Specimen dimensions and all included anatomical structures should be recorded to document how radical a resection has been performed. The tumour site, laterality, local extent and distance to margins should be described. Midline tumours may be associated with bilateral or contralateral lymph node involvement due to anastomoses in midline lymphatic vessels47 and midline and clitoral tumours have a worse prognosis.48 Tumour size should be recorded as maximum horizontal extent; a second horizontal dimension in a plane perpendicular to the first may be provided but is not required.49 The maximum depth of invasion can be estimated macroscopically once the specimen is sliced. Uninvolved skin should be examined for any abnormality.
The specimen should be serially sliced transverse to the long axis of the specimen at 3 mm intervals. Submitted sections should include tumour with the deepest point of invasion, interface with adjacent epithelium, margins, uninvolved skin and any abnormality remote from the tumour. If no tumour is identified, the entire specimen should be submitted.50 Margins can be sampled longitudinally or circumferentially/en face depending on the size of the specimen, proximity of tumour to margins and local preference. An annotated specimen photograph or diagram is an extremely useful adjunct to recording the block allocation key51 (figure 8).
This vulval wide local excision is received with an orientating suture (A). The margins are differentially inked and the specimen photograph annotated with the block allocation key (B). in this case, as no discrete tumour is visible, the entire specimen has been submitted.
Macroscopic examination and sampling of obstetric hysterectomy specimens
Hysterectomy performed at caesarean section is usually in the setting of an obstetric emergency such as intractable haemorrhage, uterine rupture or abnormal placental implantation. The placenta may or may not be included and the principles of handling such specimens are as described for the non-gravid uterus (see section on macroscopic examination and sampling of hysterectomy and other uterine specimens) and placenta. Prior to proceeding, relevant clinical and imaging findings should be reviewed to establish the expected pathology.52 The uterus should be weighed and measured in the usual way and specimen photography routinely performed; ideally this should include an image of the anterior and posterior surfaces and an inferior/vaginal view documenting the presence or absence of the cervix and whether the placental disc or cord are visible at the uterine opening.52 The presence, site and size of any lacerations, rupture with or without protruding placenta and incisions, noting whether these are open or sutured, should be documented.39 Evidence of recent or past caesarean section should be noted. In placenta accreta spectrum disorders, the uterus typically shows elongation and bulging of the lower uterine segment, thinned anterior uterine wall, and may show dehiscence of caesarean section scar and/or surgical disruption.53 Inking of non-peritonealised surfaces, particularly the lower uterine segment, with any areas suspicious for placenta percreta or prior caesarean section scar inked a different colour will assist with histological assessment.52
The plane of opening the uterus, either sagittal or coronal, should be chosen to optimise sectioning of any obvious abnormality. Probing the uterine cavity prior to opening will help guide the incision. If there is placenta previa, placing the initial cut to avoid cutting the placenta and then probing to locate the uterine cavity is recommended. On opening the uterus, the presence, location and extent of any abnormal placentation should be described and the opened specimen photographed prior to sectioning52 (figure 9). The uterine wall should be serially sliced to identify areas of abnormal placentation and/or wall thinning. If placenta increta/percreta is identified, document the site and extent of invasion relative to landmarks such as the cervix, lower uterine segment and cord insertion. It may be useful to lay out and photograph involved slices from fundus to cervix to document the extent of involvement.
This example of an obstetric hysterectomy for placenta percreta demonstrates bulging of the lower uterine segment with placental tissue protruding through a defect anteriorly (A, defect at forcep tips). A midline sutured surgical incision is also visible. The opened uterus demonstrates areas of myometrial thinning (B, arrow).
In addition to routine sections of the cervix and uterine corpus, any recent or old caesarean section site should be sampled as should the edge of any traumatic rupture. Retained placenta may appear as ragged haemorrhagic tissue lining the uterine cavity and should be sampled, including the interface of the placenta and uterus. In placental adhesive disorders, full thickness sections in composite blocks from the uterine wall to demonstrate the placenta, invasive interface and myometrium should be taken. Areas of transition from shallow to deep invasion should be targeted, aiming to demonstrate other features such as prior caesarean section scar.52 A minimum of four blocks from the interface has been suggested including a block from the deepest point of invasion.52 The principles of placental sectioning are as described below. Sampling should include the cord and membranes, full-thickness sections of the placental disc, the uteroplacental interface, any focal lesions and area of retroplacental haemorrhage.
Macroscopic examination and sampling of placental specimens
In 2016, the Amsterdam Placental Workshop Group Consensus Statement proposed an internationally agreed-upon approach to placental macroscopic examination, sampling, terminology and diagnostic criteria.54 This document, authored by a group of internationally recognised placental and perinatal pathologists, together with protocols from the Royal College of Pathologists (the UK and Australasia),55 56 forms the basis of the guidance provided here.
Pathological placental examination is indicated in a range of clinical scenarios based on fetal, maternal, obstetric and placental factors; these are well documented elsewhere and are not further discussed.55–57 Receipt of the placenta in the fresh or fixed state should be documented. Tissue for ancillary microbiological, viral or genetic studies should be collected from the fresh specimen if clinically indicated. The placental weight is a surrogate for placental function58 and is typically recorded as the trimmed weight (placental disc is trimmed of membranes and umbilical cord), noting removal of any tissue for ancillary investigations, the completeness of the maternal surface and whether the weight is taken in the fixed or fresh state; fixation increases placental weight by up to 8%.59 Contemporary placental weight standards relevant to the local population should be cited.54 The placenta may be examined and dissected in the fresh or fixed state depending on local practice. Examination in the unfixed state may aid macroscopic detection of abnormalities but increases the risk of transmission of infection.54 55
The placental disc is measured in three dimensions comprising the maximum linear dimensions in two perpendicular planes and the minimum and maximum placental thickness. The shape of the disc should be described, noting the presence and dimensions of any accessory lobe and the completeness of the disc. The umbilical cord length, average diameter, insertion site and distance of the insertion from the nearest placental margin should be recorded; the presence of velamentous, marginal or furcate cord insertion should all be noted. The appearance of the cord, including its colour, number of coils per centimetre and presence, location and size of knots, strictures or tethering to the fetal surface should be documented and the number of vessels recorded. The colour, clarity, texture and completeness of the membranes should be described together with the presence and percentage involvement of the circumference by circumvallate or circummarginate membranous insertion. Any plaques, nodules or vessels in the membranes should be described; if a vessel is identified, measure its length and document any haemorrhage indicating rupture. The closest distance of the membrane edge to the placental disc should be measured. The appearance of the maternal surface—completeness, any adherent or deforming blood clots or masses should be noted. The appearance of the fetal surface including colour and presence of any visible thrombi should be documented. The placental parenchyma should be serially sliced and the parenchyma systematically examined. Any grossly identified lesions should be described, and measured in terms of largest size (alternatively three dimensions) and estimated percentage of the placental parenchymal volume represented by the lesion. The number of lesions and their location in the disc (central 2/3, peripheral 1/3, maternal surface, fetal surface) should be stated.
Submission of a minimum of four blocks is recommended.54 One block should comprise a membrane roll taken from the ruptured edge of the extraplacental membranes to the placental margin and two transverse sections of the umbilical cord, one from the fetal end and the other 5 cm from the insertion point. At least three full thickness sections of normal-looking placenta should be submitted.54 These should be taken from the central two-thirds of the disc, including one section adjacent to the insertion site; in some centres, a routine marginal block including maternal and fetal surface and the membrane insertion is taken together with two central sections.56 If the disc sections are too thick to fit in a cassette, the tissue can be bisected and submitted as composite sections in two blocks. In addition, one block from each lesion seen should be submitted.54 In the setting of pre-eclampsia or fetal growth restriction, a decidual plate shave parallel to the maternal surface can be taken in attempt to identify maternal vascular pathology.55 Any cord lesion should be sampled.
The same principles apply to examination of twin placentas. The presence of identifying clamps as designation of birth order should be recorded. For dichorionic twin placentas, it should be documented whether the placental discs are separate or fused and a ‘T-section’ of the dividing membrane taken to confirm chorionicity. For monochorionic placentas, the fetal surface should be inspected and the location and distance between the two umbilical cords noted with identification of the vascular equator and the relative proportion of the associated placental territory as a percentage of the discs estimated for each twin. Following description and sectioning of the cord and membranes, division of fused placentas along the vascular equator and separate weighing can be performed.56 In cases of suspected twin-twin transfusion syndrome, injection of coloured dyes may be performed in the fresh state to confirm the presence of vascular anastomoses. In addition to routine sections, a section from each twin’s portion of the disc and the dividing membrane should be submitted.
Lymph node specimens
Lymphadenectomy is undertaken with many of the procedures described above; lymph nodes should be sent in appropriately labelled specimen containers detailing the various anatomical sites and handled separately. These specimens generally consist of one or more pieces of fibrofatty tissue. Recording the size of the specimen itself is not necessary, although this is often done. Identification of lymph nodes requires careful palpation and gentle dissection of the fat (with fingers or a blade). A small amount (1 mm) of fatty tissue can be left attached to the node surface; this can help in identifying extranodal spread. Lymph nodes identified grossly should be described in terms of number and size (either the largest individual node size or a range of sizes can be provided).
Lymph nodes should be sectioned at 2 mm intervals, perpendicular to the longest axis of the node. The 2 mm interval is critical as it will theoretically allow identification of any nodal metastasis measuring at least 2 mm (macrometastasis).60 Sectioning should be complete, transecting the node resulting in several pieces, each 2 mm thick. Any abnormal areas (obvious tumour, haemorrhage, cystic formation, necrosis) should be described including their maximum size; the size of metastatic nodal disease is important for staging and management.61 Any lymph node 2 mm or less in size should be left unsliced and submitted intact.
All grossly normal lymph nodes should be submitted entirely for histological examination. Multiple small, unsliced lymph nodes can be placed in the same block (the number of nodes in the block should be recorded). Each lymph node that is bisected or serially sliced should be submitted in a separate block or blocks depending on the size and number of the slices. Slices from more than one lymph node should not be submitted in the same block. Lymph nodes grossly involved by tumour can be sampled representatively, including sections with the largest macroscopic tumour area. Macroscopic handling of sentinel lymph nodes follows the approach outlined above, although obviously subsequent histological examination is significantly different.
Recommendations for the handling of excess, macroscopically normal fatty tissue vary. ISGyP recommendations for cervical carcinoma state this may be trimmed and not submitted33 while others (RCPath) advocate submission of all excess adipose tissue to a maximum of five additional blocks.34 If no lymph nodes are identified, all tissue should be submitted. The block allocation key should state the number of lymph nodes in each cassette and whether adjacent blocks are from the same node.
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References
Footnotes
Handling editor Murali Varma.
Contributors All authors contributed equally to this manuscript. WGM: Conception, planning, design, writing. CP-H, KLT: Planning, design, writing.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.