• Diagnostic biopsy

• Therapeutic resections

• Obstetrical specimens.

Section Codes

It is important that every department settle on a numbering system that is clear and used consistently throughout the specimen. The most common systems in use today are computer generated, providing the accession number for the overall case, the container sub-number for each portion of the specimen when it is received in multiple parts, an identifier for each paraffin block, the level within each paraffin block, and the type of stain used with any given slide.

Most systems use a one- or two-letter prefix to identify the general type of case received (S = surgical, C = cytology, A = autopsy), followed by a two-digit number designating the year (00 = 2000), followed by a sequential digit number. One system, in common use worldwide, then assigns a unique letter to each container received, starting at the beginning of the alphabet, i.e., ‘A.’ Each block sampled from that specimen/container then receives a sequential number, e.g., A1, A2, . . . An. Each subsequent specimen/container receives the next available letter, e.g., B, with multiple blocks from the container having sequential numbers, B1 . . . Bn. If multiple levels of a single paraffin block are made, a practice for cervical biopsies in many institutions, the letter ‘L’ is appended with the designation of the slide level, e.g., -L2 for the second level of the block. Thus a typical specimen number might be SG-00-02167 B4-L2, which translates to ‘Surgical specimen of a gynecologic nature, received in year 2000, accession number 2167, container B, fourth block taken from specimen B, and second slide prepared from that paraffin block.’ Variants of the above system typically utilize letters in upper and lower case, Roman numerals, and Arabic numbers, usually in some combination and defined sequence. Of course, multiple numbering systems exist, and it is not the purpose of this chapter to pick which is best; the purpose is rather to help ensure clarity in whatever system is used.

Location of Section Codes in the Report

Most pathologists prefer a section code summary at the end of the gross text while some prefer entering block codes within the gross text. In either case, the report must be clear, both to the pathologist and to any person who at a later time will need to utilize the report. Block summaries, if used, may duplicate substantial parts of the gross, but cannot be used in its place. Including the block submission within the body of the gross description may be easier and more efficient for the person cutting in the specimen: ‘The borders in one region are sharp and distinct from the surrounding myometrium (Block B10) while elsewhere it blends into the adjacent myometrium (Block B11).’ However, having a section key at the end of the dictation may make histologic examination easier and more efficient. If the block codes are listed sequentially at the end of the report, the specific site and feature identified require presentation in sufficient detail so that the reader can easily link the gross description with the slide. Using the example above, it would be inappropriate for the coding block at the end to state that B10 and B11 are myometrium as it is unclear which section has the sharp borders and which has blurred borders. A section code at the end might better read, ‘B10 Myometrium, sharply circumscribed medial border, B11 Myometrium, blurred indistinct borders.’

Specimen and Site Identification

Regardless of the section code method used, it is critical that the reader can link the tissues received to the sections processed and both to the final diagnoses. For example, four cervical biopsies from the same patient are received in separate containers, but from the same operation. Information on the requisition slip indicates that the colposcopically directed specimens are from 3, 6, 9, and 12 o’clock, respectively. In this example, the accession number might be SG-00-02167, and the containers labeled A, B, C, and D, respectively. Since the paraffin block usually is identified solely by the code, then this same code should appear throughout. Thus, the gross might read ‘A. 3:00 bx’ (the wording exactly replicating what the clinician wrote on the container itself) while the final diagnosis would include ‘A. Cervix, Biopsy at 3 o’clock: Diagnostic finding.’ Obviously, the label on the slide must provide all of the necessary identifiers.

A most perplexing problem we encounter in referred specimens is where the label assigned to the container in the gross description differs from that given in the microscopic description to that given in the final diagnosis. For example, the container might be ‘A’ in the gross description, which refers to a specimen consisting of uterus, ovaries, and fallopian tubes, whereas the final diagnosis is ‘1. Endometriosis of the ovary.’ Such cases require substantial effort on the part of the consultant pathologist to determine (and sometimes guess) which gross description truly belongs to which slide and both to the listed final diagnosis.

Gross Description

If possible, describe specimens received in the fresh state before fixation. Formalin alters natural color and consistency of tissue. The opening sentence of the gross description should indicate how the tissue is received (fresh or fixed) and labeled. Does the specimen received correspond with its label? For example, the container received states ‘Uterus, tubes, and ovaries,’ yet the left adnexa is absent. Such a gross description might read, ‘Received fresh is a uterus and right ovary and fallopian tube. The left ovary and fallopian tube are absent.’ Give measurements and weights of the individual diseased organs (e.g., ‘the 710 g, 18 × 15 × 8 cm uterus’). Conglomerate measurements and weights are meaningless (uterus, tubes, and ovaries which together weigh 710 g and measure 18 × 15 × 8 cm) since they are ambiguous as to the role played by each organ and where the pathology resides.

The gross description should proceed in an orderly fashion, focusing on the primary lesion. Several common methods are in use. In one, the pathology in any given container/specimen is emphasized first. This highlights the pathology and de-emphasizes the normal. In practice, descriptions are full but economical in words and space. The second method is to follow a routine pattern whereby the same order is followed in every case, e.g., ovary, fallopian tube, uterine corpus, cervix, etc. This method, while usually easier for the novice, lends itself to loquacious reports filled with tedious description. All too often the true pathology is treated least well or even inadequately, as it is buried deep in the description. Not uncommonly, such travelogues lead to reports several pages long, but with a description of the tumor under several lines in toto. With the novice, detailed descriptions force careful examination, but, with experience, can be refined to a more concise and readable form.

Avoid elaborate descriptions of normal incidental anatomy. In a radical hysterectomy for cervical cancer, there is no need for an overly elaborate description of a normal fallopian tube. The following is excessive, ‘7 cm long, elongate structure with a 1 mm internal diameter and 4 mm external diameter with a tan, smooth, glistening serosa, a 2 mm thick wall, and a lumen without identifiable abnormality.’ Simply ‘the fallopian tube is 7 cm long, 4 mm in diameter and unremarkable’ will do.

Similarly, we believe experience should allow the pathologist to describe grossly obvious lesions in diagnostic terms rather than nonspecific and frequently long-winded descriptions, a practice with which many also disagree. Leiomyoma, or, where useful, the diagnostic term with one or two adjectives (‘well-circumscribed, whorled leiomyoma lacking hemorrhage or necrosis’), is far more useful than the excessive description (‘numerous, discrete, circumscribed, rounded lesions with a bulging whorled cut surface, white in color, and compressing the adjacent myometrium’), which is tedious to read. At worst the description is vague (‘rounded lesions’). Purposeful uncertainty, where it exists, can also be introduced with adjectives (‘5 cm soft, focally necrotic leiomyomatous nodule with irregular borders suspicious for sarcomatous change’).

The gross description, especially of small specimens, should conclude by stating how much of the tissue has been processed for microscopic examination. This is especially important in the case of endometrial curettings removed for a suspected intrauterine pregnancy where neither chorionic villi nor other tissues of fetal origin are found and all of the tissue has been submitted. Specify the number of each type of block sampled and from where each was obtained. An example of a useful gross description is ‘The endometrium, which is 2 mm thick, discloses no obvious tumor. The entire endometrium including the superficial myometrium is blocked and submitted in toto.’

Inking

Application of ink, often in multiple colors, can be useful to identify various surgical margins, which on histologic sections is helpful to determine if the lesion is truly present at the margin or is present only where the tissue has been cut on a bias, thus simulating a margin (ink absent). If used, apply ink sparingly and blot dry to prevent spillover or running. Acetone or distilled white vinegar can be used to set the ink. As inking is a procedure all too often done indiscriminately, determine first whether it is even useful. There is no need to ink a uterine serosa in cases of cervical squamous intraepithelial lesions (SIL) or in cases where the endometrial cancer is small and noninvasive and the serosa is obviously normal and uninvolved. Ink sometimes is helpful (and sometimes the only clue) in identifying the surface of the ovary when replaced by tumor. Ensure also that the ink does not inadvertently conceal disease, e.g., endometriosis or a metastasis on the serosa.

Drawings and Photographs

The inclusion of drawings and/or photographs may simplify portrayal of complicated relationships and permits better orientation, especially of surgical resection margins. Today, most photographs use digital technology. Document scanners can also be used for this purpose and can create surprisingly high-quality images. Block diagrams made from digital photographs or Xerox copies are particularly useful in complex cases. In the absence of actual photographs, diagrammatic drawings of the specimen and sections taken can also be helpful.

Fixatives

Formalin-based fixatives are generally the most practical and commonly used today. Tissue submitted in blocks for processing should be less than 3 mm thick. Thicker fragments are difficult to dehydrate and inhibit paraffin infiltration, thus leading to suboptimal slides. Sometimes, it is much easier to cut sections from tissue that has been fixed for several hours instead of attempting to cut 3 mm thick slices directly from a fresh specimen. Large specimens should be cross sectioned and cut at intervals 1 cm thick or less. This permits adequate penetration by formalin, after which the tissue can be trimmed into 3 mm thick sections. For large specimens, e.g., uteri removed for leiomyomata, placing the tissue blocks into cassettes (with all labeling complete) and retaining them in the fluid fixative for an extra day facilitates better sections. If fresh or frozen tissue is required for special studies, this should be collected prior to fixation.

Number of Sections Required

Judging what must be sampled to optimally examine a specimen is one of the more controversial subjects not only in gynecologic pathology, but in all branches of surgical pathology. In general, the authors believe that far too many blocks are usually taken, adding expense without furthering diagnostic information gained. A useful exercise is to determine what single slide would be taken if the entire prosection permitted were limited to the single slide. This forces thinking about which single slide would demonstrate the lesion as well as pertinent margins or neighboring relations. Such forethought often has a major influence on how a specimen is opened and/or sampled. For example, an excisional biopsy of vulvar tumor might be best sampled by six equidistant perpendicular blocks sampling the central tumor, deep margin, and lateral margins rather than eight parallel lateral margins, shave margins of the base, and only several of the tumor. Leiomyomas/equivocal leiomyosarcomas should include not only the tumor but also the border with neighboring tissue and margins if possible. Endometrial tumors can easily be sampled to include the adjacent ‘normal’ endometrium.

Synoptic Checklists

As the complexity of information contained in reports increases and tumor cases are accessioned into trials with specific entry criteria, checklists are being used with increasing frequency to record and evaluate the details of operative and pathologic findings consistently. A full listing of College of American Pathologists specimen processing protocols, including synoptic checklists, is available online at www.cap.org.

Excisional Biopsies

Biopsies of the vulva should be handled like skin biopsies. Assess the deep and lateral resection margins. If the surgeon has placed a suture for orientation, inking (often in several colors) facilitates recognition on microscopic examination.⁴

Wide Local Excision

In general, wide local excisions are performed for noninvasive neoplasms such as vulvar intraepithelial neoplasm (VIN) 3 or Paget disease of the vulva, as well as superficially invasive (less than 1 mm) stage 1 carcinomas. Lymph node dissections are added for stage 1B carcinomas (greater than 1 mm invasive). Orientation is critical in these specimens and, if not clearly indicated, consultation with the surgeon may be required. Operative specimens often include labia minora and majora, clitoris, perineal body, and perianal tissue (Figure 35.1). Describe and measure the lesions, distances to resection margins, and the anatomic structures involved. Examine the coloration and surface texture carefully as intraepithelial lesions are subtle, typically red-brown to white and roughened.

As intraepithelial lesions are often multifocal and difficult to discern macroscopically, all surgical peripheral and deep resection margins should be evaluated microscopically. Sections parallel to margins (‘tangential’) may be taken to evaluate the excision lines; however, one difficulty commonly encountered in parallel sections for evaluation of margins is to determine if tumor found in the slide truly involves the margin or was from the inner face, and therefore not a true representation of the margin.

For discrete tumors, such as squamous cell carcinoma, multiple full thickness sections perpendicular to the skin surface and radiating outward from the lesion are advantageous as the central lesion, margins, and intervening areas can be included in one slide and tumor close to the margin is easy to evaluate (Figure 35.2). Facilitate sectioning by pinning the specimen on a corkboard or a block of paraffin and fix for several hours or overnight. Diagrams or photographs are often useful.

Skinning Vulvectomy

This is by definition a superficial excision of the vulvar skin at the level of the dermis, meaning it is performed almost entirely for noninvasive neoplasms (VIN 3 and Paget disease). The gross description and sections taken will be similar to those of wide local excision.

Simple (or Total) Vulvectomy

This includes the entire vulva and subcutaneous fat (dissection to deep fascia). It is typically performed for noninvasive neoplasms that widely involve the vulva. Pin, fix, and section the specimen at 0.5 cm intervals to evaluate for invasive carcinoma. Typically, the extent of Paget disease exceeds that visible macroscopically as occult foci are often present within normal-appearing skin. The resection margins must be thoroughly evaluated.2,5

Radical Vulvectomy

Radical vulvectomy consists of vulva excised to the deep fascia of the thigh, the periosteum of the pubis, and the inferior fascia of the urogenital diaphragm. It is most commonly performed together with at least an inguinal lymph node dissection, which may be included en bloc with the vulvectomy. Total radical vulvectomies have largely been replaced in favor of more limited excisions, but sufficient to completely excise the primary tumor with a minimum 2 cm margin. Radical total vulvectomies are now performed primarily for large and/or aggressive tumors. The gross description should include the size, location, depth of invasion, and all resection margins, including perianal and vaginal margins. Sections should include the tumor, showing the maximum depth of invasion, labia majora and minora, clitoris, distal urethra, resection margins including the vaginal margin, and all lymph nodes. Separate lymph nodes into superficial and deep groups, and submit all lymph nodes entirely for histologic examination (unless grossly positive; in that case a representative section is sufficient). Invasive vulvar neoplasms are typically solitary in contrast to intraepithelial lesions, which are often multifocal. Consequently, evaluation of resection margins can be largely limited to the margins closest to the tumor. The report should include microscopic diagnosis, tumor grade, dimensions, location and maximum depth of invasion, presence of lymphatic invasion, number and location of involved lymph nodes, and distance to resection margins. Diagrams and/or photographs may be useful aids.

Punch Biopsies

Biopsies are usually colposcopically directed. The best specimens are at least several millimeters long with underlying stroma to a depth of 2–4 mm. If the fragments are tiny, they can be placed in a mesh bag for processing. Record the number of pieces received. The fixed, curled biopsy may be bisected transversely to produce two pieces that are approximately pyramidal in shape. These are then embedded with the flat, cut surface downward so that this surface is cut by the microtome. Step-serial sectioning is not necessary routinely.

Endocervical Curettage

Endocervical curettage is performed to evaluate the presence of glandular neoplasms, cervical squamous neoplasia involving the endocervical canal, or to determine whether endometrial carcinoma has spread into the cervix. Endocervical scrapings should be submitted as a separate specimen in a mesh bag before being placed into the cassette to avoid loss of small fragments of tissue during processing.

Cervical Cone Biopsy/Excision and Trachelectomy

Cone biopsy is the standard procedure performed for women with high-grade SIL and glandular lesions. The cone biopsy can be a diagnostic or a therapeutic procedure. Commonly, it is both simultaneously. The conventional cone biopsy is obtained using a scalpel (‘cold knife’) but, today, is often done with laser or low-voltage, large-loop diathermy methods (LEEP). Excision with loop diathermy has the advantage that there is usually less bleeding and the cervix heals with better preservation of anatomy. It can also be performed as an outpatient procedure without the need for general anesthetic. One disadvantage, especially if the instrument is used at suboptimal power levels, is thermal damage that may make diagnosis and, in particular, the examination of margins difficult. Trachelectomy may also be performed as a therapeutic procedure for early stage invasive carcinomas of the cervix. A trachelectomy is a more extensive version of a cone excision, as the entire cervix is removed, with or without a vaginal cuff.

The cone biopsy is a roughly cone-shaped excision of the uterine cervix to include a portion of exocervix, external os with the entire transformation zone (T-zone), and endocervical canal with varying amounts of deep tissue. We ask the surgeon to note the 12 o’clock position with a black suture. If the specimen is not oriented, the 12 o’clock position may be arbitrarily assigned.

The surgical pathologist can limit the gross description to the measurements of the specimen and any obvious lesion. The measurements should include the cranial–caudal distance (the height or length of the cone specimen), the diameter if the specimen is not opened (Figure 35.3), or circumference and thickness if received opened. For a trachelectomy specimen, the presence of vaginal cuff should be documented and measured.

Blot dry the tissue and apply ink sparingly. Open the specimen at 12 o’clock, and pin the tissue on a corkboard with the mucosa facing up. Fixation for 3 hours before cutting is usually adequate. Serially cut sections should be sequentially submitted in cassettes numbered consecutively. Submit the entire specimen in a clockwise direction beginning at 12 o’clock (Figure 35.3). Convenience and economy dictate placing two or three sections per cassette.

Both the ectocervical and endocervical edges of the cone specimen need to be assessed. This can prove to be problematic if a specimen is bowed and cut tangentially (Figure 35.4).

Hysterectomy for Malignant Cervical Disease

Simple hysterectomy is commonly performed for high-grade intraepithelial neoplasms and many microinvasive cancers. Radical hysterectomy, which refers to the removal of paracervical soft tissue, is common for stage 1 squamous carcinomas, depending on size and configuration of the tumor in the endocervical canal, and for some stage 2A tumors.

For uteri removed for the treatment of squamous intraepithelial lesion, amputate the cervix at least 1 cm above the level of the external os and process in the way that has been described above for a cone biopsy. Often, one section from each quadrant may be sufficient. Each section should be full thickness to include the endocervical mucosa, squamocolumnar junction, exocervix, and outer adventitia. If a vaginal cuff has been submitted, measure the distance from the exocervix to the line of resection. We prefer sections perpendicular to the line of resection.

The gross description from a radical hysterectomy needs to include tumor dimensions and location—especially with respect to the vaginal fornix and the vaginal margin—depth of invasion, and an impression of whether the lymph nodes contain metastases. Sections of the cervix need to demonstrate both the maximum depth of invasion and the relationship of the tumor to the surgical margins. One or more blocks should contain a complete section from the mucosal surface of the uterus through to the serosa. Additional sections of the tumor to the non-neoplastic mucosa interface will often demonstrate SIL. The region of the internal os–lower uterine segment (LUS) should also be sampled. These sections may be taken longitudinally (upper endocervix to LUS). Submit all of the parametrial tissue since this represents the lateral and most significant resection margin. Inking the parametrium is useful. The surgeon will usually group lymph nodes by areas. If received intact and oriented, separate and group as right and left, further by location (internal iliac, external iliac, obturator, etc.).

Endometrial Biopsies and Curettings

Tissue from an endometrial biopsy (curettage or outpatient sample) should be submitted in its entirety. The gross description should estimate the aggregate volume. The cassettes should be packed loosely to permit proper fixation and dehydration. Wrap specimens in fine Shandon mesh/tea bags or equivalent and document in the dictation that the whole specimen is included.⁷

Sampling of hysteroscopically evident lesions must always be accompanied by a broader and representative sampling of the remaining otherwise unremarkable endometrial lining.

Uterus Removed for Benign or Functional Disease

This includes hysterectomy for leiomyomas, endometrial hyperplasia, persistent abnormal bleeding, uterine prolapse, or intractable pelvic pain, the last sometimes due to unrecognized organic causes, e.g., adenomyosis or endometriosis on the serosa.

List specimens received, including whether the adnexae are attached or separate. Several methods are available for orientation. One easy method to determine laterality is to lift the specimen by the two ovaries, which will be posterior to the fallopian tubes (Figure 35.5). Another method that is useful in the absence of adnexae is to observe the peritoneal reflections. The posterior uterine peritoneal surface covers a larger area and extends farther down toward the cervix in a V-shaped configuration, whereas, anteriorly, it ends higher over the bladder and in a more flat or smooth U shaped reflection edge.

Weigh the specimen without adnexae (i.e., subtract the estimated adnexal weight). Nomenclature is given in Figure 35.6.

Examine the uterine serosa, particularly the posterior surface, for adhesions or brown hemosiderin deposits, so-called ‘powder burns,’ which may indicate endometriosis, and small vesicles or gritty implanted foci suggestive of borderline serous tumor, endosalpingiosis, ovarian cancer, or psammoma body implants. Examine the exocervix for lacerations, scarring, ulcerations, and nabothian cysts.

Before opening the uterus, probe the cervical canal and endometrial cavity to establish the canal’s patency; this also facilitates opening the uterus. With scissors cut from the cervical os to the cornu along one lateral margin to the fundal top and then repeat on the opposite side. Another option is to pass a pair of long fine forceps through the cervical os all the way to the fundus and cut the uterus open by using a long knife between the forceps blades. These methods ensure that the endometrial cavity will be exposed, with the anterior and posterior endomyometrium intact.

Measure the average thickness of the endometrium and assess whether it is atrophic, polypoid, lush, or hemorrhagic, and smooth or rough surfaced. Record polyp measurements and location (fundic, anterior/posterior, near LUS, etc.). Evaluate the myometrium and state its average and maximum thickness. Focally or asymmetrically thickened myometrium, small cysts, or hemorrhage suggests adenomyosis. For a normal cervix, usually one section is adequate if it includes the entire wall to involve the endocervix, squamocolumnar junction, exocervix, and paracervical soft tissue. Some pathologists prefer one section each of the anterior and posterior lips. The section through the endometrium, if the lesion is benign, should be 2 cm long and include the full endometrial thickness and a wedge of myometrium with serosa if not too thick. Generally, two sections, one each from the anterior and posterior (or right and left) corpus, suffice if the woman is in reproductive years and one if the uterus is atrophic and the woman is in the postmenopausal years (Figure 35.7). If there is no apparent pathology and the preoperative diagnosis is pain or dysfunctional uterine bleeding, then increase the number of sections to at least four that are full thickness, and include a posterior LUS section with peritoneal reflection. It is surprising how frequently adenomyosis is confined to only a single area in a single slide.

Uteri removed for endometrial hyperplasia or precancerous lesions require multiple sections of the endomyometrium to exclude carcinoma. For example, six sections, each 2 cm long and cut as wedges, can usually fit into two or three cassettes (Figure 35.8). If the uterus is not enlarged, this number of sections often samples 75% of the endometrium. Some pathologists prefer to block in the entire endometrium with sections through to the serosa so as not to miss the possibility of invasive cancer and be able to measure the depth of invasion.

Uteri removed for leiomyomas should have documented the number of leiomyomas present, their location (submucosal, intramural, subserosal) and size (e.g., ‘ten measuring ≤ 1 cm and two measuring 13 and 18 cm in diameter’). If submucosal, state whether the tumor distorts the endometrial cavity or protrudes into the lower uterine canal or cervix. Each leiomyoma should be sectioned and examined grossly, but not necessarily microscopically. If all are small, white, firm, whorled, with well-circumscribed margins, and lack areas that are soft, necrotic, or hemorrhagic, even one block can be sufficient. Routine microscopic examination of every typical leiomyoma is unnecessary. Conversely, as leiomyosarcomas generally grow as a single nodule or mass and exhibit soft and degenerative areas, any suspicious areas should be thoroughly sampled. As a rule, of the suspicious regions take one microscopic section per 1 cm of the nodule’s greatest dimension, for these areas usually yield more useful information. The transition between smooth muscle tumors and surrounding myometrium is the preferred site for histologic sampling. ‘Random’ sections of grossly typical leiomyomas generally are of little use. For myomectomy specimens, transect each leiomyoma and take one section of each if the number is not excessive, or more if any areas are suspicious. More commonly, hysterectomies for benign conditions are being performed laparoscopically with morcellation. In this situation, the morcellated uterus should be weighed and examined to identify fragments with endometrium, serosa, cervix if present, and lesional tissue (leiomyomas, adenomyosis, etc.), and a conservative number of blocks submitted.

Supracervical Hysterectomy

Supracervical hysterectomy is sometimes performed for benign uterine disease such as leiomyomas. These may be processed as discussed earlier; however the ‘endocervical’ margin of excision must be inked to document the level of transection, and representative sections of this margin submitted for histologic examination.

Malignant Uterine Disease

Evaluate all specimens with a preoperative diagnosis of malignancy for residual tumor. If present, determine the maximum depth of myometrial invasion and cervical involvement (mucosal or stromal) and take sections to document these findings.

The gross description must include the size, location, distribution (focal or diffuse), and shape (sessile or polypoid) of the lesion. For example, ‘a 6 × 5 cm sessile anterior endometrial tumor involves the anterior LUS but not the endocervix. The tumor grossly invades 5 mm and maximally 10 mm into a 23 mm thick wall (approximately 45% of the myometrial thickness).’ If the tumor is polypoid and protrudes into the endometrial cavity, identify the borders of the adjacent normal endometrium, draw an imaginary line between, and then report measurements above and below the line. Thus the 1 cm thick tumor, which protrudes 7 mm into the endometrial cavity, penetrates 3 mm into the superficial myometrium (Figure 35.9). Describe and sample the uninvolved endometrium, including its relationship with the tumor and adjacent myometrium. At least one microscopic section should permit measurement of the greatest depth of tumor invasion, and may be submitted as two blocks if the full myometrial thickness does not fit in one cassette (Figure 35.10). For intramural tumors, describe and sample the interface between the tumor and myometrium (circumscribed, irregular, or infiltrative) and note any worm-like extrusions of tumor in surrounding tissues that could represent grossly involved lymphatic/vascular channels (seen most commonly in endometrial stromal sarcomas and intravenous leiomyomatosis). An endometrium previously ablated for precancerous disease need not be entirely submitted; representative sections in addition to any grossly identifiable lesion should be submitted for microscopic examination.

Lymphadenectomy may be included in the staging of endometrial carcinoma. Studies have shown that higher numbers of removed pelvic and para-aortic lymph nodes (12 or greater) are more prognostically powerful, particularly when negative.⁸ Thus, careful dissection of lymphadenectomy specimens, with submission of all possible lymph nodes, is necessary.

Endometrial Sampling for Products of Conception

For specimens with obvious aborted products of conception, evaluate completeness of fetal and placental removal when possible. Therapeutic abortions, if performed after week 8, will more often show fetal fragments than spontaneous abortions. Single small samples of fetal parts and placenta suffice for sectioning. When fetal parts are absent, pay particular attention to finding chorionic villi. Chorionic villi are soft gray-white tissue fragments that arborize when submerged in fluid. Soft, tan, solid, and often shiny gray tissue is decidua and, in itself, does not diagnose the presence of an intrauterine pregnancy.

At times, the specimen may consist of a uterine cast. Look for an intact or ruptured gestational sac in spontaneous abortions especially. Embedding a portion of the sac with the embryo in agar may improve the chances of observing it microscopically. When a fetus or fetal parts are identified grossly, usually one section is sufficient for documentation, unless there is a gross abnormality. Note crown–rump length and head circumference of the fetus, if possible, and obtain the weight. Since the fetus is often disrupted in therapeutic abortions, another measurement useful to assess fetal age is the toe–heel (foot) length. Only if microscopic examination fails to reveal tissues of fetal origin should additional tissue be processed. Avoid submitting blood clots; in contrast to ectopic pregnancy in the fallopian tube where blood clots typically contain chorionic villi, uterine blood clots almost always lack chorionic villi, even when villi are abundant elsewhere.

Curettings from hydatidiform moles often come in two parts: suction curettage and sharp curettage. Examine carefully for fetal parts. Submitting three blocks is usually sufficient. Tissue from the sharp curettage should be processed entirely, since it must be evaluated for myometrial invasion. It should also be remembered that, with suction curettage, most vesicles will have been forcibly disrupted and the classic gross appearance will not be present.

Uterus Removed during Obstetric Procedures

Hysterectomy during delivery is performed for intractable hemorrhage, placenta accreta, uterine rupture, or cervical neoplasia. For the last, process the specimen as described previously. For the other conditions, focus the gross description and sectioning on the relation of the placenta and membranes to the uterus. Describe lacerations, usually lateral, carefully as to location, extent, and depth of penetration. Uterine rupture may have occurred at the site of a previous lower segment cesarean section scar and sections across the site of rupture should be oriented to optimize its identification as a predisposing factor. Also, placenta previa, placenta accreta, and previous cesarean section in the lower segment not infrequently go together. Obtain sections from these sites. A prosector should be aware that occasionally a fetus/baby might have been delivered through the site of uterine rupture, which subsequently was sutured. If no obvious site of rupture is identified, the sutured wound should be sampled for microscopic examination after inking of the serosal surface. For placenta previa, sample carefully the zone of the internal os to identify associated placenta accreta. Suspected placental retention sites identified by strongly adherent placenta are useful in defining placenta accreta, increta, and percreta. Full thickness sections of these areas should be submitted.

Sterilization

When removed for ligation, the single most important finding is that indeed the tube has been ligated. This requires that a complete cross section of the tube, which includes the lumen, be identified grossly and confirmed microscopically. Measure the length and the diameter of each tube. One method for sampling is to slice the tube into sections 1–3 mm long and to submit all for microscopic examination, each piece being cut on end. Even if per chance some sections are cut tangentially, usually at least some will be intact to document that the lumen is present. This saves substantial time and effort by not having to request additional recuts.

Tubal Ectopic Pregnancy

Record the site and location of the pregnancy, which is often seen as a bulging area of hematosalpinx. A rupture site, if present, should be described and sampled. If the ectopic pregnancy is not obvious, a focal enlargement or swelling should be sought, and the entire tube sectioned extensively. Blood distending the lumen should be documented, as it is unlikely to result from any other cause. A tubal abortion leaves foci of trophoblast at the implantation site. Blood clot in the tube, sometimes submitted as a separate specimen, should be examined carefully for gray-white tissue and sampled microscopically for trophoblast or chorionic villi. Multiple cross sections of the fallopian tube at the site of swelling or bleeding demonstrate chorionic villi efficiently. Sections of fallopian tube, even slightly away from the swelling, may be normal, but should be sampled to confirm or exclude pre-existing pathology such as agglutinated plicae in healed salpingitis.

Prophylactic Salpingectomy (with or Without Oophorectomy)

Another increasingly common indication for salpingectomy is prophylaxis for patients who have BRCA1/2 mutations, a personal history of breast cancer, or strong family history of breast and/or tubo-ovarian cancer. Typically the specimen is grossly unremarkable; however, these fallopian tubes, along with the corresponding ovaries, should be submitted entirely for histologic examination according to the SEE-FIM protocol.⁹ The proximal fallopian tube is serially sectioned at ~3 mm intervals, stopping approximately 1 cm before the distal-most portion of the fallopian tube. The fimbria should be sectioned longitudinally to maximize fimbrial plicae histologic examination (Figure 35.11).

Tubal Neoplasm

Recent studies have shown that tubal cancer is more common than was initially appreciated, partly due to the fact that fallopian tubes historically were not thoroughly sampled for histologic examination.⁹ Tubal carcinomas behave similarly to ovarian carcinoma and frequently appear as a solid mass in the wall of a grossly dilated tube, but may sometimes only be identified upon microscopic examination. When grossly identifiable, its size, location, and extent, with reference to other pelvic structures, should be documented. Transverse sections through the full tubal wall permit determination of the depth of penetration/invasion, which is an essential component to the pathology report.

General Rules

Several general rules can be applied when the specimen is small, incidental, or where no substantial pathology is anticipated:

Large Cystic or Neoplastic Ovaries

Weighing large ovarian tumors may provide a more readily appreciable assessment of the size of the lesion. Document whether the ovarian tumor is received intact or ruptured and learn whether the rupture occurred intraoperatively (preoperative rupture can upstage the patient). If a tubo-ovarian mass is submitted, careful dissection may be necessary to identify its components. In pelvic inflammatory disease the ovary is relatively spared and should be readily recognized once the surrounding adhesions have been teased away. The course of the fallopian tubes should be identified and the condition of the fimbriae noted. A hydrosalpinx or para-ovarian cyst, especially if associated with adhesions, may cause confusion if diligent efforts are not made to establish the anatomic relationships.

Pay attention to the capsule, inking the outer surface before slicing the ovary at 1 cm or less intervals. Document if adhesions, inflammation, or tumor involve the surface. This is important in staging. Include the capsule and tumor, and include tumor with adjacent normal parenchyma. Many ovarian tumors are cystic and all locules should be opened with scissors or sliced through with a sharp long-bladed knife. Note the character of the cyst contents (serous, mucoid, bloodstained, oily, gelatinous, pultaceous) and the smoothness of its lining. A smooth shiny lining usually indicates a benign lesion, whereas solid areas or papillary excrescences may suggest a more worrisome lesion and thus should be extensively sampled. Ragged hemorrhagic cyst linings suggest endometriosis. Mature cystic teratomas (dermoid cysts) should be emptied as completely as possible of the trapped hair and sebaceous material. Remove sebum by washing with hot water (liquefies the sebum).

Look for the fallopian tube, which may be incorporated in or stretched over the tumor mass/cyst. It may contain coexistent neoplasia.

For small tumors, identify the location as cortical, medullary, or hilar. If mucinous, find the most solid regions and sample extensively. The cystic areas will be benign or microscopically disclose little more than borderline tumor. Only the solid areas generally show areas definable as adenocarcinoma.

If the ovary has undergone torsion, the tissues may be extremely edematous, hemorrhagic, or even necrotic. Slice the ovary finely, looking for any viable tissue or residua of a cyst or solid tumor that may have undergone torsion. Reticulin stains on suspicious areas may help to highlight the underlying pathology. The accompanying fallopian tube, if also involved, should be closely examined because it may be, albeit rarely, the site of the inciting lesion. In children, torsion of normal adnexa is not uncommon.

Microscopic Sections

Ink can be useful to document the tumor’s serosal surface. The best blocks of tumor are where the tissue is viable. Generally, about one block per 2 cm of greatest tumor dimension will suffice to document the tumor process. It is common in cystic mucinous neoplasms for any single tumor to have large areas that are benign or borderline, with only few areas that are unequivocally malignant. Commonly, areas with multilocular thin-walled cysts are benign, or at most of borderline malignancy. Areas that are more solid are usually borderline and sometimes frankly malignant. Quite commonly, only 10% of solid areas may show unequivocal malignancy, which in a 10 cm tumor translates to only two slides with malignancy out of 20 sampled. Search diligently for solid areas and sample them thoroughly. Unilocular cysts with a smooth inner-wall lining may be large, but require few sections. Membrane rolls composed of extensive quantities of cyst wall tissue can be examined if the wall is made into a membrane roll and a cross-section slide prepared (Figure 35.13).

Germ cell tumors should be sampled extensively, especially if they appear grossly heterogeneous. If there is a history or clinical suspicion of intersex an X-ray for calcifications may indicate an area of gonadoblastoma. These regions should be sampled thoroughly. All variations in the gross appearance such as foci of hemorrhage or necrosis should be specifically sampled as they may represent different tumor types, e.g., foci of embryonal carcinoma or yolk sac tumor (YST) arising in association with a dysgerminoma.

Dermoid cysts should have microscopic sections taken from the solid tissue. These are the business components, and the ones that will disclose the carcinoid, strumas, etc.

Staging Operations

There is need for close cooperation between surgeon and pathologist in the staging operations for assessment of both primary ovarian carcinoma and for previously treated cancer. These may involve intraoperative assessment of excised tissues, including frozen section, as well as the histologic examination of multiple specimens and cytologic assessment of peritoneal washings and ascitic fluid. General guidelines for the surgeon include the following:

Specimens submitted for pathologic examination are likely to include the following:

Second Trimester Fetus

In many institutions, special permission is required to examine a fetus nearing viability. Statutes variously define the cut-off as a fetus older than 20 weeks’ gestation, greater than 15 cm crown–rump length, or greater than 300 g weight. Regardless of gestational age, the placenta can be submitted as a surgical pathology specimen.¹¹

Pathologic examination of fetuses varies by clinical context and local resources. Generally, a voluntarily aborted ‘normal’ fetus will be handled differently than intrauterine demise for unknown reasons or a fetus that carries a specific antenatal diagnosis. In particular, formal fetopsy may be indicated when the intent is to discover cause of death or evaluate a suspected congenital syndrome. If indicated, sterile samples for cytogenetics or culture should be taken prior to fixation. Whenever possible in these cases the placenta should be evaluated in conjunction with the fetus. This section reviews generally applicable grossing and sampling procedures, which will be modified by clinical circumstance.

Physical integrity (intact, fragmented) and autolytic state (well preserved, macerated) of the fetus should be recorded. Extent of fetal maceration may be helpful in documentation of the time frame of fetal demise. Measure and record the fetal weight, crown–heel length, crown–rump length, and head circumference. Other common measurements include foot length, thorax, and abdominal circumferences. Sex can usually be determined by external examination. If the genitalia are ambiguous, then describe them as such. Never give a ‘best guess’ for sex assignments. Look for obvious external anomalies, and if present consider whether they may be part of a multi-feature syndrome that requires targeted examination of visceral abnormalities. More subtle ones are difficult to observe in early gestation. Measure the attached cord length and state the number of blood vessels. Describe the skin surface and, after the body is opened, observe the organs in situ. Determine situs and note any obvious abnormalities. Retrieve the gonads and place them in a mesh bag at this point. Take sections of various organs. Weighing organs that are part of a fragmented surgical specimen is often a futile exercise. Microscopic sampling should include each lobe of lung, both gonads, and small sections of every other organ including stomach and other various parts of gastrointestinal tract and skin. Macerated fetuses are difficult to sample adequately because of the severe softening of the tissues; submit sections of more solid tissue (lungs, heart, kidneys). Often the entire examination consists of no more than three cassettes filled with tissue.

Placenta

Abnormalities of the placenta are frequently associated with adverse outcomes in either the fetus or the mother.11,12 Examination of the placenta is not routinely performed in most institutions unless specific indications are present. The CAP practice guidelines include recommendations of indications for placental examination (Table 35.1). To determine which placentas should be examined, remember the three funnies: funny mother, funny infant, funny disease. This should lead to the examination of about one in three placentas, although in practice fewer are examined (about one in five).¹¹

If indicated, sterile samples for cytogenetics or culture should be taken prior to fixation. Fresh samples should also be taken for metabolic/biochemical studies and/or electron microscopy.

Identify the site of membrane rupture. If far from the placenta proper, consider it to be unremarkable and make no comment. If there is a membranous cord insertion or large fetal vessels traverse the membranes, note their relation to rupture site. Record the presence or absence of hemorrhage in the membranes, and the approximate distance of it to the margin of the placenta.

Remove the free membranes and cord, leaving the fetal side of the disc undisturbed, and weigh the placenta (Table 35.2). Measure the disc diameter. Systematically describe all parts (Figure 35.14).

1. Lester, SC. Manual of surgical pathology, 3rd ed. Philadelphia: Saunders; 2010.

2. Schmidt, WA. Principles and techniques of surgical pathology. Menlo Park: Addison-Wesley; 1983.

3. Westra, WH, Hruban, RH, Phelps, TH, Isacson, C. Surgical pathology dissection: an illustrated guide. New York: Springer; 2003.

4. Greene, LA, Branton, P, Montag, A, et al. Protocol for the examination of specimens from patients with carcinoma of the vulva. http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Vulva_12protocol_3101.pdf, 2012. [>/;].

5. Black, D, Tornos, C, Soslow, RA, et al. The outcomes of patients with positive margins after excision for intraepithelial Paget’s disease of the vulva. Gynecol Oncol. 2007; 104:547–550.

6. Kalof, AN, Dadmanesh, F, Longacre, TA, et al. Protocol for the examination of specimens from patients with carcinoma of the uterine cervix. http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Cervix_12protocol.pdf, 2012.

7. Movahedi-Lankarani, S, Gilks, CB, Soslow, R, et al. Protocol for the examination of specimens from patients with carcinoma of the endometrium. http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Endometrium_12protocol.pdf, 2012.

8. Lutman, CV, Havrilesky, LJ, Cragun, JM, et al. Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology. Gynecol Oncol. 2006; 102:92–97.

9. Crum, CP, Drapkin, R, Miron, A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol. 2007; 19:5.

10. Oliva, E, Branton, PA, Scully, RE. Protocol for the examination of specimens from patients with carcinoma of the ovary. http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Ovary_12protocol.pdf, 2012.

11. Kraus, FT. Introduction: the importance of timely and complete placental and autopsy reports. Semin Diagn Pathol. 2007; 24:1–4.

12. Curtin, WM, Krauss, S, Metlay, LA, Katzman, PJ. Pathologic examination of the placenta and observed practice. Obstet Gynecol. 2007; 109:35–41.