|Year : 2020 | Volume
| Issue : 4 | Page : 378-387
Grossing and reporting of squamous cell carcinoma of oral cavity—An evidence-based approach
KR Anila1, Cessal T Kainickal2, Shaji Thomas3, K Jayasree1
1 Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
2 Department of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
3 Department of Surgical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
|Date of Submission||20-Jun-2020|
|Date of Decision||12-Jul-2020|
|Date of Acceptance||08-Sep-2020|
|Date of Web Publication||02-Oct-2020|
K R Anila
Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala
Source of Support: None, Conflict of Interest: None
The grossing of radical surgery specimens of the head and neck region is extremely challenging due to the complicated anatomy with the inclusion of various tissues such as mucosa, soft-tissue, bone, skin, etc., in the specimen. Also, essential/core data provided in the histopathology report significantly influence further treatment decisions taken. The eighth edition of the cancer staging manual of the American Joint Committee on Cancer has brought about major changes in reporting of squamous cell carcinoma of the oral cavity. Though pathologists in oncology centers who routinely handle such specimens are aware of these updates and the impact of their report on patient management, this may not be true for other peripheral centers that may be handling these specimens. Lack of awareness can lead to a compromised report which will adversely affect patient management. This article attempts to discuss the salient features to be noted in grossing and reporting of squamous cell carcinoma of the oral cavity and the rationale behind this.
Keywords: Grossing, oral cavity, reporting, squamous cell carcinoma
|How to cite this article:|
Anila K R, Kainickal CT, Thomas S, Jayasree K. Grossing and reporting of squamous cell carcinoma of oral cavity—An evidence-based approach. Indian J Cancer 2020;57:378-87
|How to cite this URL:|
Anila K R, Kainickal CT, Thomas S, Jayasree K. Grossing and reporting of squamous cell carcinoma of oral cavity—An evidence-based approach. Indian J Cancer [serial online] 2020 [cited 2020 Oct 24];57:378-87. Available from: https://www.indianjcancer.com/text.asp?2020/57/4/378/297028
| » Introduction|| |
Grossing is the cornerstone of surgical pathology. Despite many advances in the field of pathology, for example, immunohistochemistry and molecular techniques, the quality and completeness of a histopathology report are still heavily dependent upon how well a specimen has been sampled and processed. No amount of advanced technology can compensate for the shortcomings brought about by a compromised grossing.
Cancer of the oral cavity is one of the common cancers in India. Grossing of radical surgery specimens done for cancers of the oral cavity, depending on the extensiveness of surgery can be challenging due to the complicated anatomy. In almost all cases of radical surgery done for squamous cell carcinoma (SCC) of the oral cavity, a histopathological diagnosis of SCC would have already been rendered in a previous biopsy. So, pathologists should be aware that the information our clinical colleagues require from these specimens are details that directly impact the prognosis and staging, such as pattern of invasion, margin status, depth of invasion, perineural invasion (PNI), lymphovascular invasion (LVI), bone involvement, etc. These details are absolutely essential for prognostication of individual cases and planning further treatment. If the histopathology report does not include these details, it will adversely affect patient management.
This article does not intend to give a step-by-step account of the grossing but attempts to discuss the salient features in handling radical surgery specimens of SCC of the oral cavity, the essential data to be included in the histopathology report, including the clinical relevance of such information. A brief discussion on reporting neck dissection specimens which usually accompany the radical surgery specimens and a mention of the use of frozen section in surgery of SCC of the oral cavity is also included.
| » Prerequisites for Submitting Specimens|| |
It is mandatory for specimens to be accompanied by request forms containing all relevant clinical details. Apart from the patient identity, details like type of surgery done, the site or sites involved including laterality, the clinical tumor, nodes, metastases, etc., should be provided. These details can be verified at the time of grossing and any discordance can be sorted out in consultation with the operating surgeon. Preoperative treatment history, that is, radiation or chemotherapy history should be mentioned. These neoadjuvant therapies can influence the gross appearance and affect the pT stage. If a bone is part of the resection, then radiological details should also be provided.
The specimens should be transferred to 10% neutral buffered formalin without delay. The containers should be wide-mouthed and there should be adequate formalin. The specimens should be tagged with surgical sutures so that orientation is easy at the time of grossing. Each institution should have a standard code for the orientation sutures. In our center, we follow the code short tag for anterior margin and long for the lateral margin. Double tags are sometimes placed by our surgeons when they find suspicious areas that require additional attention by a pathologist. The requisition forms as well as specimen containers should contain details regarding the area indicated by each orientation/surgical suture as practices can vary from institution to institution as well as among surgeons.
| » Handling of Gross Specimens of Head and Neck Cancer|| |
The type and extent of surgery done in SCC of the oral cavity depends on the size of the lesion and extent of the disease. The main aim of surgery is to achieve locoregional clearance, that is, total removal of disease with adequate margin. SCC can involve any one subsite or can extend to adjacent subsites. Various subsites of the oral cavity include the anterior two-thirds tongue (oral tongue), upper alveolar ridge, lower alveolar ridge, retromolar trigone (RMT), buccal mucosa, floor of the mouth, hard palate, lip (mucosal lip begins at the junction of the vermillion border with skin and includes a portion of the lip that comes in contact with an opposed lip). Portion of lip in continuity with skin is staged similar to skin cancer and not as that for oral cancer.
Types of specimen usually encountered in oral cavity cancers
Wide excisions are done for early-stage cancers of the tongue and buccal mucosa wherein the lesion along with the surrounding tissue is removed with adequate margin clearance [Figure 1]a.
|Figure 1: (a) Wide excision specimen of early disease of the tongue with orientation sutures. (b) Segmental mandibulectomy specimen for growth in the gingivobuccal sulcus. (c) Hemimandibulectomy specimen for growth involving alveolus and buccal mucosa|
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Wide excisions with marginal mandibulectomy: wide excision of the primary lesion along with a portion of mandible. Marginal mandibulectomy is done when the lateral margin of a wide excision specimen of the tongue is close, so that for achieving an adequate margin clearance, portion of the mandible needs to be excised. Marginal mandibulectomy is also done for early lesions of the gingivobuccal sulcus and in early cancer of alveolus when there is only superficial erosion of the mandible by the tumor without cortical invasion. In such cases, there is no need to remove a portion of the mandible in full-thickness. Bony margins in marginal mandibulectomy will include anterior, posterior, and inferior/deep margins.
Segmental mandibulectomy: is done when there is clinical and radiological evidence of bone involvement. Segmental mandibulectomy is the removal of full thickness of the portion of mandible. It will have anterior and posterior bony margins [Figure 1]b.
Hemimandibulectomy: is also done when there is clinical and radiological evidence of bone involvement. It includes removal of one half of the full thickness of mandible. Also, for large tumors with a high T-stage, hemimandibulectomy is needed for adequate clearance. Even without clinical or radiological evidence of bone involvement, sometimes a portion of the mandible has to be removed for achieving adequate margin clearance, especially when there is gross paramandibular spread. Hemimandibulectomy specimens will have an anterior bony margin [Figure 1]c.
Extended hemimandibulectomy: More than half of the mandible is removed.
Middle-third mandibulectomy: Full thickness of the middle portion of the mandible is removed. This procedure is done when growth involves lower anterior alveolar ridge, anterior gingivolabial sulcus, and anterior floor of the mouth or lower lip. This specimen will have two lateral bony margins.
Hemimandibulecomy along with a portion of the maxilla: This radical surgery is done when there is an extension of growth from RMT to upper alveolus or upper gingivobuccal sulcus/palate. This necessitates removal of the upper alveolus with a portion of maxilla and clearance of the infratemporal fossa along with hemimandible.
| » Steps in Grossing|| |
Identify and orient the specimen
Orient the specimen with help of orientation sutures. Make sure that it is in concordance with the information in the request form. Any disparity has to be sorted out in consultation with the operating surgeon prior to the starting of grossing. Also, for complicated specimens with difficulty in orientation, help should be taken from the surgery team. Based on the extent of disease, the specimen can be just a wide excision or a more radical procedure including the mandible, maxilla, soft tissue, skin, etc. Identify the type of resection, including all the anatomical subsites in the specimen.
Note the location (tongue, lip, alveolus, buccal mucosa, gingivobuccal sulcus, retromolar trigone, floor of mouth, palate) including laterality, and note the gross dimension and distance from surgical margins. If soft tissue, skin, and bone are present in the specimen, note whether there is an extension of growth to skin, bone, or soft tissue. The dimension of bone, skin, etc., is to be recorded. Note the gross appearance of the growth, whether verrucous, ulceroproliferative and exophytic, or ulceroindurative. Ideally, grossing should start only after multiple specimen photographs are taken in different angles after identification and inking of margins. This is helpful if there is a need to reorient the specimen after grossing. Specimen radiography, if required, should also be performed prior to grossing. Cut through the growth, making multiple parallel slices at 5–10 mm intervals perpendicular to the long axis, and note the third dimension and distance from the deep margin. Multiple serial sections are done so that we do not miss the maximum depth to which the tumor has infiltrated. Submit entire sections from growth. A full-thickness section of the tumor with the deep margin should be submitted, after inking the deep margin [Figure 2]. This is essential for reporting the depth of invasion (DOI), which is an essential data to be included in the histopathology report. In addition to this, radial margin at the periphery should also be submitted. If the tumor is so big that an entire section cannot be submitted in one cassette, the section can be halved and submitted.
|Figure 2: Section to be taken of growth with deep margin so that depth of invasion (DOI) can be accurately measured|
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Many times after cutting through the growth, it is noted that the external distance recorded from margins may not be correct because there will be a submucosal extension and margins can be closer than noted in external examination. So, it is better to measure the gross margin clearance after taking serial sections. Margin clearance is an important feature to be incorporated in the histopathology report. Ideally, a section of growth with margin should be taken radially after inking the margins with Indian ink. We, at our center, apply glacial acetic acid after inking the mucosal and soft tissue margins with Indian ink. This will ensure that the ink stays and does not get washed off during processing and can be appreciated on microscopy. The advantage of a radial margin is that in spite of only a small portion of margin being sampled, the exact microscopical clearance can be measured and included in the final histopathology report.
Bone involvement is an important factor that will upstage the disease to pT4a. In gross examination, even if the bone appears involved or uninvolved, sampling is mandatory and sections from growth with the bone are to be submitted for histologically documented evidence. Similarly, depending on the type of bone resection, bony margins are to be submitted. Hemimandibulectomy will have only anterior bony resection margin whereas a segmental resection of the mandible will have both anterior and posterior bony margins, and a marginal resection of the mandible will have anterior, posterior, and deep bony margins. Bone margins can be taken as shave margins using a bone saw.
When skin is part of the resection, gross examination should be made to comment on skin involvement should be made. Sometimes skin involvement is quite evident with ulceration of overlying skin. However, often, there is retraction of the skin due to inflammatory response/fibrosis and this may clinically mimic involvement. Adequate sampling along with skin margins is essential for correct diagnosis as the involvement of skin will upstage the disease to pT4a.
Sections to be submitted
- Tumor: covering the entire cross-section
- Margins: radial mucosal margins after inking with Indian ink and fixing with glacial acetic acid (anterior, posterior, medial, lateral, deep margins).
- Decalcified bone sections: from bone underlying/close to the growth and bony margins depending on the type of resection
- Skin: overlying skin and closest skin margin
- Soft-tissue margins.
Essential data to be incorporated in histopathology report of squamous cell carcinoma of the oral cavity
Type of surgery and specimen
Type of resection including laterality should be specified. When the bone is present whether it is hemi, segmental, or marginal mandibulectomy. When a portion of the maxilla is also part of the resection, it should be mentioned. All anatomical subsites included in the specimen should be mentioned. The exact location of growth should be mentioned.
The microscopic tumor dimension is an integral or essential data to be included in the pathology report. It is known that there can be a disparity in tumor dimension in gross examination and microscopy. Often, the microscopic dimension is more than the gross dimensions.
Type of cancer
Conventional SCC is most common. The variants of SCC are verrucous, basaloid, spindle cell, papillary, adenosquamous, lymphoepithelial, acantholytic, hybrid (verrucous with conventional SCC), and carcinoma cunniculatum. Specify the variant because it is important in prognostication. Subtypes like spindle cell, acantholytic and adenosquamous carcinoma are known to be associated with a bad prognosis compared to conventional SCC.,,, Verrucous and papillary subtypes are associated with a better outcome than conventional SCC., Human papillomavirus (HPV)-positive SCC is more common in the oropharynx. HPV can be associated with oral SCC in a small number of cases, however, unlike in HPV-associated oropharyngeal cancer; the prognostic implications of HPV in oral cancers are unclear.
SCC is graded as well, moderate, or poorly differentiated. It is based on features such as keratinization, nuclear pleomorphism, mitosis, pattern of invasion, and host response., If the tumor has varying degrees of differentiation/grade, the highest grade should be reported. For example, if there are well-differentiated and moderately differentiated areas in the same tumor, report as moderately differentiated carcinoma. Subtypes of SCC such as verrucous carcinoma, papillary SCC, basaloid SCC, sarcomatoid carcinoma, etc., need not be graded because each of the subtype itself serves as a prognostic indicator. Conventional histological grading correlates poorly with clinical outcomes. Grading as an independent factor does not correlate with prognosis.
Pattern of invasive front
It has been proved that the pattern of growth at the advancing front of the tumor is closely associated with the clinical outcome, especially in early-stage disease, that is, T1 and T2.,, The pattern is assessed at the invasive front of the tumor, that is, at the tumor-stroma interphase. A cohesive front is associated with a better outcome compared to a non-cohesive pattern. The more the loss of cohesion more will be the aggressiveness of the tumor. Cohesive invasion is defined as tumor nests more than 15 cells across. The non-cohesive pattern can include strands, small groups of fewer than 15 tumor cells, and single infiltrating tumor cells.
Worst pattern of invasion (WPOI 5) is characterized by tumor satellites 1 mm or more from the main tumor or nearest satellite [Figure 3]a. There is evidence in the literature which confirms that in low-stage oral cavity SCC (T1, T2) with more than 4 mm DOI, the presence of WPOI-5 is significantly predictive of locoregional recurrence and disease-specific survival and the probability of developing locoregional recurrence is almost 42%., WPOI is a validated outcome predictor for oral cavity squamous carcinoma patients in multivariate analysis. Dispersed extratumoral PNI, or extratumoral LVI, also can qualify for classification as WPOI-5.
|Figure 3: (a) WPOI 5 showing tumor satellites with more than 1 mm distance between them. (b) To measure DOI, the basement membrane is identified, and an imaginary line is drawn across the tumor. A vertical or plumb line extends to the deepest part of the tumor, which represents the DOI. (c) Perineural invasion showing tumor cells wrapped around the perineurium. (d) Microscopy of a resected margin showing the India ink|
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There are five patterns of invasion: Type-1—pushing border, type-2—finger-like growth, type-3—large separate islands, more than 15 cells per island, type-4—small tumor islands, 15 cells or fewer, per island, type-5—tumor satellites, equal to or greater than 1 mm away from the main tumor [20×] or next closest satellite. To simplify prognostication and enhance compliance, the recommendation as of now is to report whether WPOI-5 is present or not.
Depth of invasion: DOI in oral cavity SCC is an important prognostic indicator and is an essential data to be included in the report.,, AJCC in its latest cancer staging manual, the 8th edition has incorporated DOI as an essential data to be reported for determining the T stage. DOI is measured microscopically from the basement membrane to the deepest point of invasion. DOI measures the invasiveness of the carcinoma and hence will be different for an exophytic and endophytic tumor. To measure DOI, the basement membrane is identified and an imaginary line is drawn across the tumor. A vertical or plumb line extends to the deepest part of the tumor, which represents the DOI [Figure 3]b. Determination of DOI is not always easy, as the basement membrane is not always a straight line. In cases where the basement membrane is undulating, try to extrapolate to an area where it is comparatively straight. When we compare an exophytic tumor and an ulcero-indurative tumor, the ulcero-indurative tumor may be thinner but DOI is more and hence associated with a bad prognosis. The incorporation of DOI in determining the T-stage reflects the importance of DOI. It is important to understand that tumor thickness and DOI are different and not synonymous. DOI increases pT by one step for every 5 mm. DOI is reported in millimeters.
pT1: is tumor 2 cm or smaller and DOI 5 mm or less.
pT2: is tumor more than 2 cm, but not more than 4 cm and DOI more than 5 mm and upto 10 mm.
pT3: is tumor larger than 4 cm or any tumor more than 10 mm DOI.
pT4a: is tumor larger than 4 cm along with DOI more than 10 mm or tumor invading adjacent structures (through cortical bone of mandible or maxilla or involves the maxillary sinus or skin of the face).
pT4b: is a very advanced local disease with the involvement of masticator space, pterygoid plates, skull base or encasing the internal carotid artery.
We can understand the significance of incorporating DOI into the T stage by this example. Tumors with a diameter of 4 cm in surface dimensions, but DOI over 10 mm that would previously be staged as T2 will be migrating to T3 due to the incorporation of DOI in determining T stage and hence these cases will be of stage-III in the overall staging. Thus, tumors that required single modality treatment has been upstaged and would now require multimodal treatment, making a pretreatment determination of the DOI important. When there is a doubt between a higher and lower value of DOI, it is better to communicate the difficulty to the clinical colleagues so that decisions on escalating or de-escalating treatment in the particular case can be appropriately taken.
Perineural invasion: PNI is a factor that adversely affects prognosis and is an essential data to be included in the histopathology report., Care should be taken while reporting PNI. The tumor should wrap around the perineurium. Entrapped nerve bundles without the involvement of perineurium should not be reported as PNI [Figure 3]c. This is critical because, in presence of PNI, patient will receive radiotherapy and there are instances when other adverse factors are not present in a particular case, wherein decision for adjuvant therapy is taken based on the presence of PNI alone.
Though not part of the essential data, there are data suggesting that the size of the nerve bundle involved may have a role in predicting the outcome. So, the size of the nerve bundle involved whether less than 1 mm or more than 1 mm must be specified in the report. Also, the location of PNI, whether away from the tumor proper (extratumoral) or within the tumor proper (intratumoral) appears to have a role in determining the outcome, with PNI away from the tumor proper having a worse outcome.,, Whether PNI is unifocal or multifocal should also be included in the histopathology report.
Lymphovascular invasion: LVI is also an indicator of a bad prognosis., It is identified by the demonstration of malignant cells within the lumina of blood vessels and/or lymphatics. It is important to distinguish between intravascular tumor embolization and fixation and/or processing retraction artifact. In difficult cases, immunostains with CD31, (V-ets erythroblastosis virus E26 oncogene homolog) can be done to establish whether it is an artifact or true LVI. The presence of LVI is an indication for adjuvant radiotherapy.
Margins: Margin status, the clearance obtained by surgery is an important indicator for predicting outcome in SCC of the head and neck region., In head and neck surgeries due to anatomical constraints, a clearance of more than 5 mm is accepted as adequate [Figure 3]d. Clearance of 1–5 mm is taken as a close margin. Less than 1 mm clearance or tumor at the inked surgical margin is a positive margin. It is also important to report regarding dysplasia at the margin. High-grade dysplasia at the margin is a positive margin and is managed accordingly. Depending on the type of specimen, a comment should be made not only on mucosal margins but also on bone, soft-tissue, and skin margins. A close or involved margin warrants re-excision or adjuvant chemoradiation. Chemotherapy in SCC of the head and neck region is associated with high morbidity, so care should be taken in reporting margin status. Identification and re-excision of a particular margin in an already operated case is also difficult.
Bone: Bone involvement is an adverse prognostic indicator. It is important to know that superficial cortical erosion does not justify a histopathological report of bone involvement. The tumor should invade through the cortical bone which will upstage the disease to pT4a. It is mandatory to confirm bone involvement microscopically even if it is evident on gross examination so that the evidence is documented histologically. Bone margins should also be commented upon depending on the type of specimen. Involvement of bone warrants subsequent radiotherapy.
Skin: When specimens with skin are submitted, report should include whether the skin is involved or not and also on skin margin status. The involvement of the skin needs further treatment with radiotherapy.
[Table 1] summarizes the data to be incorporated in the reporting of the SCC of the oral cavity.
|Table 1: Histopathology features to be incorporated in report of squamous cell carcinoma of oral cavity|
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Neck dissection specimens
This section intends to give an idea about the salient features to be included in the reporting of neck dissection specimens. A detailed discussion on this topic is beyond the scope of this article. Frequently, oral cavity excision specimens are accompanied by neck dissections. Radical neck dissection removes levels I to V lymph nodes along with the sternocleidomastoid muscle, spinal accessory nerve, and internal jugular vein. Modified radical neck dissection removes all the lymph node levels included in radical neck dissection but spares at least one or more of the non-lymphatic structures. An extended neck dissection involves the removal of lymph nodes or non-lymphatic structures in addition to those removed as part of radical neck dissection. A selective neck dissection is a more limited procedure, which spares one or more of the lymph nodes from levels I to V.
The selective neck dissection includes supraomohyoid neck dissection, lateral neck dissection, and posterolateral neck dissection. Supraomohyoid neck dissection refers to the removal of levels I to III and is commonly performed for tumors of the oral cavity. The yield of nodes is usually not a problem. A minimum of 15 nodes in a comprehensive neck dissection specimen and 10 nodes in selective neck dissection is expected. However, the recent recommendation from the American Society of Clinical Oncology (ASCO) requires at least 18 lymph nodes for neck dissection to be considered adequate. The different levels of lymph nodes should ideally be submitted separately in different containers. If due to any circumstance the neck dissection specimen is being submitted en bloc, it is essential to mark the different levels with surgical sutures so that the nodes at different levels can be submitted separately during grossing. In case orientation sutures are not present, pathologists can orient the specimen with available anatomical landmarks and submit the different levels of nodes separately.
The total number of lymph nodes in each level confirmed microscopically has to be separately noted and recorded along with the number of nodes in each level showing metastasis. It is important to note the size of the largest node with metastasis as well as the size of the largest metastatic focus. If metastasis is present, then it is extremely important to comment on extranodal extension (ENE). According to the eighth edition of the AJCC cancer staging manual, it is now mandatory to report on ENE of metastasis as it will upstage the N stage. ENE refers to the extension of the tumor outside the capsule of a lymph node and into the perinodal soft tissue. ENE is a poor prognostic factor in cervical node-positive head and neck carcinoma., For assessing this in microscopy, during grossing care should be taken to submit the entire cross-section of the node.
The presence of ENE in head and neck cancers correlates with the risk of regional recurrence and risk of distant disease. It is an indication for postoperative radiotherapy or chemoradiotherapy. In case there is metastasis at a particular level with ENE, postoperative radiotherapy can be directed to that particular location. This will not be possible when neck dissection specimens are submitted en bloc and different levels are not identified separately. Less than 0.2 mm ENE is considered as microextension and more than that is macro-extension.
| » Role of Frozen Section in Head and Neck Cancer Surgery|| |
There are centers including ours, which utilize intra-operative frozen section consultation for assessing margin status in surgeries of head and neck cancer. The advantage is that, if margins are close, a revision surgery can be done then and there. Re-excisions at a later date or need for adjuvant therapy can be thus avoided. It should also be taken into consideration that positive or close margins are a strong indicator of disease recurrence. In head and neck cancers the margin clearance is measured in millimeters, with more than 5 mm clearance being adequate. Such minimal clearance may be influenced by tissue shrinkage due to formalin fixation. Using intraoperative frozen studies for margin assessment can overcome the effect of formalin fixation. In cases wherein there is a grossly good margin clearance of more than one centimeter, in our experience the margins were usually free on frozen section examination also. However, rarely we were able to diagnose dysplasia and skip lesions by doing frozen in cases where grossly the margins appeared free.
Guidelines for adjuvant treatment in oral cancer
Stage I (pT1N0) and stage II (pT2N0) without adverse features are considered for follow-up after surgery. However, patients with stage I and II with adverse histopathological features like PNI and lymphovascular emboli are considered for adjuvant radiotherapy. Stage III (pT3 N0, pT1-3N1) and stage IVa (pT4aN0, pT1-4N2) require adjuvant radiotherapy as a planned treatment. The standard adjuvant radiotherapy dose is 60 Gy/30 fractions. Patients with ENE and margin positivity require post-operative chemo-radiation. The standard dose of radiotherapy in this setting is 66 Gy/33 fractions along with concurrent cisplatin 100/m2 given once in three weeks. Postoperative chemoradiation is a very toxic treatment and requires rigorous monitoring during and after treatment. Thus, pathologists should be aware of the implications that the histopathology report has on patient management.
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Conflicts of interest
There are no conflicts of interest.
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