The Core Data in Histopathology Specimens

Specimen dissection must be geared to provide information relevant to the clinician who is managing the patient. Reports must be timely, i.e., prompt, but in the context of an adequate period of fixation so that acquisition of accurate data is not compromised. The report content must not only come to an interpretationally accurate diagnosis but also be qualified by assessment of various prognostic indicators. In the field of surgical cancer pathology this is reflected by the trend towards set-format reports or minimum datasets for the common cancers. Thus, the core content should include gross specimen description, tumour histological type and grade, extent of local tumour spread, lymphovascular invasion, lymph node involvement, relationship to primary excision margins and any associated pathology.

Gross description: Clear distinction should be made between biopsy and resection specimens as they are handled differently and represent different nodal points in a patient's illness. This should be reflected in the use of appropriate SNOMED T (topography) and P (procedure) codes - this also facilitates audit of biopsy and resection - proven cancer numbers and correlation with other techniques such as cytology, radiology and serum markers. The site, distribution, size, edge and appearance of a tumour within an organ greatly influences the specimen handling and creation of a diagnostic short list for microscopy. For example, a gastrointestinal malignant lymphoma may be multifocal, pale and fleshy with prominent mesenteric lymphadenopathy whereas a carcinoma is more usually ulcerated and annular, firm and irregular with more localised lymph node disease and vascular involvement.

Histological tumour type: There are marked prognostic and therapeutic differences between the diagnoses of carcinoma, sarcoma, germ cell tumour and malignant lymphoma. This is further highlighted within a given anatomical site, e.g., lung, where a diagnosis of carcinoma can be of various subtypes requiring either primary surgical (squamous cell carcinoma) or chemo-/radio-therapeutic (small cell carcinoma) approaches and with very different biological outcomes.

Histological tumour differentiation or grade: Tumour differentiation or grade reflects the similarity to the ancestral tissue of origin and degree of cellular pleomorphism, mitoses and necrosis. It, too, greatly influences choice of therapy and prognosis, e.g., low-grade versus highgrade gastric lymphoma (antibiotics versus chemotherapy/surgery) or grade I (surgery alone) versus grade III (surgery and chemotherapy) breast cancer.

An accurate histological tumour type and grade cannot be ascertained unless there is appropriate specimen handling with adequate fixation.

Extent of local tumour spread: Prognosis of a given cancer may be influenced by the character of its invasive margin (circumscribed/infiltrative) but is largely determined by its pathological stage, i.e., the depth or extent of spread in the organ and degree of lymph node involvement. This is then updated by other information, e.g., evidence of distant metastases, to formulate a clinical stage upon which management is based. The TNM (Tumour Nodes Metastases) classification is the international gold standard for the assessment of spread of cancer and translates into hard data some of the descriptive language used in histopath-ology reports, facilitating communication within the multidisciplinary team. The post-surgical histopathological classification is designated pTNM and is based on pre-treatment, surgical and pathological information.

pT: requires resection of the primary tumour or biopsy adequate for evaluation of the highest pT category or extent of local tumour spread. Due to tumour heterogeneity this is contingent upon adequate numbers of well-orientated blocks. Where possible, multiple tumours are individually staged and the highest pT category used for management decisions. pT0: no histological evidence of primary tumour. PTis: carcinoma in-situ.

pT1-4: increasing size and/or local extent of the primary tumour histologically. pN: requires removal of nodes sufficient to evaluate the absence of regional node metastasis and also the highest pN category. Where possible all regional nodes in a resection specimen should be sought and harvested for histology. pN0: no regional lymph node mestastasis histologically. pN1-3: increasing involvement of regional lymph nodes histologically.

pM: requires microscopic examination of positive body cavity fluid cytology or distant metastases - the latter may not be available to the pathologist and is therefore designated on clinical or radiological grounds.

Other descriptors include unifocality (pT1a) versus multifocality (pT1b), lymphatic invasion (L), venous invasion (V), classification during or after multimodality therapy (ypT), recurrent tumour (rpT) and multiple primary tumours (pTm). Qualifying tumours in the TNM system are carcinoma, malignant mesothelioma, malignant melanoma, gestational trophoblastic tumours, germ cell tumours and retinoblastoma.

Lymphovascular invasion: Usually defined histologically in blocks from the tumour edge or slightly away from it and more likely to be associated with cancers that show local recurrence, lymph node involvement, submucosal spread and satellite lesions. This has implications for blocking of resection specimens and their margins. Some cancers (hepatocellular carcinoma, renal cell carcinoma) have a propensity for vascular involvement and care should be taken to identify this on gross specimen dissection and microscopy as it alters the tumour stage and is a marker for distant haematogenous spread.

Lymph nodes: The pN category relates to the total node yield and the number that are involved. Nodal yields are used to audit the care of dissection by the pathologist, adequacy of resection by the surgeon and the choice of operation, e.g., axillary node sampling versus clearance in breast cancer. All regional nodes should be sampled and although ancillary techniques exist (xylene clearance, revealing solutions) there is no substitute for time spent on careful dissection. Care should be taken not to double count the same node, and those small nodes (> 1 mm with an identifiable subcapsular sinus) in the histological slides immediately adjacent to the tumour should not be ignored. TNM rules state that direct extension of primary tumour into a regional node is counted as a nodal metastasis as is a tumour nodule with the form and smooth contour of a lymph node in the connective tissue of a lymph drainage area (e.g., mesorectum) even if there is no histological evidence of residual lymphoid tissue. A tumour nodule with an irregular contour is classified in the pT category, i.e., as discontinuous extension. Dissection and submission of separate deposits is therefore important. When size is a criterion for pN classification, e.g., breast carcinoma, measurement is of the metastasis, not the entire node and will usually be made from the histological slides. Micrometastases (< 2 mm) are designated pN1 (mi) and isolated tumour cells (< 0.2 mm) pN0 as they are not regarded as having metastatic potential. Most busy general laboratories submit small nodes (< 5 mm) intact or bisected and a mid-slice of larger ones. Additional slices are processed pending microscopy. The limit node is the nearest node to the longitudinal and/or apical resection limits and suture ties. Some specimens, e.g., transverse colectomy, will have more than one and they should be identified as such. Extracapsular spread is an adverse indicator more usually recognised histologically but should be noted on gross inspection if near to or impinging upon a resection margin, e.g., axillary clearance in breast carcinoma.

Excision margins: The clearance of excision margins has important implications for patient follow-up, adjuvant therapy and local recurrence of tumour. Measurements should be made on the gross specimen and checked against the histological slide. Painting of the margins by ink supplemented by labelling of the blocks is important. Paint adheres well to fresh specimens but also works on formalin-fixed tissue. India ink or alcian blue are commonly used. Commercially available multi-coloured inks are helpful particularly if there are multiple margins as in breast carcinoma. If the intensity of the colour on the slide is low it can be easily checked against the paraffin block. Paint is usually applied to margins prior to dissection but can be re-applied for further emphasis after obtaining the block along its edge. The relevance of particular margins (longitudinal, quadrant, transverse, circumferential and anatomical) varies according to specimen and cancer type and is further discussed in their respective organ systems. In general terms, involvement of longitudinal margins can be by direct, discontinuous or multifocal spread, e.g., oesophageal carcinoma. Positive circumferential radial margins are an indicator of potential local recurrence and a gauge of cancer spread, local anatomy and the extent of surgical excision. Peritoneal or pleural serosal disease allow potential trans-coelomic spread to other abdominopelvic organs, or transpleural spread to the chest wall.

TNM classifies local resection as:

R0: No residual tumour.

R1: Microscopic residual tumour (proven by tumour bed biopsy or cytology) and in effect if tumour involves (to within < 1 mm) the resection margin. R2: Macroscopic residual tumour.

Other pathology: Predisposing, concurrent and associated conditions should be noted, blocked and documented, e.g., colorectal carcinoma and adenomatous polyps, gastric carcinoma and gastric atrophy or synchronous malignant lymphoma (MALToma).

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