Evaluation of suspected malignancies

Author: Mikael Häggström
For evaluation of suspected malignancies such as tumors, the most important aspect is whether it is benign or malignant. If malignant, then staging is necessary. There are generally specific criteria for various forms of tumors, which should be used whenever applicable, but following are some generalizations.

A general approach is to start looking at the slide which seems to contain most tumor (excluding any necrosis), facilitating a diagnosis, and shows what kind of cells to look for in the periphery.

Benign or malignant

Cellular features of malignant cells versus normal cells.

	Benign	Malignant
Gross examination	Well demarcated from surrounding tissue	Usually no tumor capsule Possibly: Necrosis Infiltration or invasion into surrounding tissue Bleeding
Microscopy	Almost no irregularities of cellular structures	Nuclear atypia: Enlargement Pleomorphism Nuclear polychromasia, which means variability in nuclear chromatin content. Numerous mitotic figures

Overall diagnosis

For specific diagnoses by organ system, see anatomic diagram on Patholines Main page. This resource will give the main steps towards reaching a diagnosis, but before making a tumor diagnosis, always confirm with The WHO Classification of tumors, and generally an experienced pathologist as well until you feel confident.

Two relatively common forms of tumors are:

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  Gland-like tumors (image shows normal colonic crypt compared to an adenoma)

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  Spindle-cell tumors (image shows a leiomyoma)

Gland-like tumors are mainly evaluated for cellular atypia, architectural dysplasia and invasion, and thereby classified into the following main categories:

• Hyperplastic lesions, lacking significant atypia
• Adenomas, which can range from mild to high-grade dysplastic, yet are not invasive
• Adenocarcinomas, with the main criterion being invasiveness. Evaluate specifically by location when possible. Some specific locations included in this resource:

• Colorectal adenocarcinoma
• Prostate adenocarcinoma
• Lung adenocarcinoma
• Bladder adenocarcinoma
• Esophageal adenocarcinoma
• Endometrial adenocarcinoma

For Spindle-cell tumors, the shape of the nuclei is a clue to the diagnosis, with the following tendency:

• Pointed on both ends: True fibroblastic tumors
• Pointed on one end and blunted on the other ("bullet-shaped"): Neural
• Blunted on both ends ("cigar-shaped"): Smooth muscle
• Triangular: Myofibroblastic

Evaluate specifically by location when possible, such as spindle-cell tumors of the midgut.

Further pinpointing of a specific tumor type is often attained by thinking of one or more possible diagnoses, and looking up their differential diagnoses, followed by comparing their microscopic descriptions and multiple micrographs with the case at hand. When two or more diagnoses seem to fit with the case at hand, consider performing immunohistochemistry. Find relevant target proteins that are expected to stain substantially differently between the possible diagnoses. If it's not evident from initial sources, you may use Immunoquery.com which will generally suggest the most relevant target proteins to distinguish the suspected conditions at hand.

Staging

Staging is generally done by TNM classification. Specific TNM systems should be used whenever applicable, mainly the manual by the American Joint Committee on Cancer (AJCC) if you can access it. Further information: Secrets . Otherwise, a general system may be used:

T: size or direct extent of the primary tumor Tx: tumor cannot be assessed Tis: carcinoma in situ T0: no evidence of tumor T1, T2, T3, T4: size and/or extension of the primary tumor N: degree of spread to regional lymph nodes Nx: lymph nodes cannot be assessed N0: no regional lymph node metastasis N1: regional lymph node metastasis present; at some sites, tumor spread to closest or small number of regional lymph nodes N2: tumor spread to an extent between N1 and N3 (N2 is not used at all sites) N3: tumor spread to more distant or numerous regional lymph nodes (N3 is not used at all sites) M: presence of distant metastasis M0: no distant metastasis M1: metastasis to distant organs (beyond regional lymph nodes)

Put your main focus on features that will determine the final stage. For example, if you see a lymph node involved by cancer, the presence or absence of lymphatic invasion is no longer critical, but rather the presence or absence of additional involved nodes or distant metastasis.

Radicality

If tumor is seen at edge of the sample, but it is not inked, consider confirming the finding with adjacent microtomy levels, especially if no ink is seen on an inked surgical margin. In this case, a separation artifact in top image has removed a surgical margin of connective tissue, seen on adjacent microtomy section in bottom image.

Determine if malignant cells are located close to, or even in, any surgical resection margins.

Lymphovascular invasion

Lymphovascular invasion should always be mentioned. When present at margins, it does not count as tumor extension.

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  Endometrial cancer with lymphovascular invasion.

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  If unsure whether a case is true lymphovascular invasion or a retraction artifact (imaged), use immunohistochemistry for D2-40 to highlight lymphatic vessels or CD-31 for blood vessels.

Typing and grading

Also note "treatment effect", seen as fibroelastotic tissue, here with scattered remaining tumor cells.

Beyond determining overall malignancy diagnosis (such as adenocarcinoma), probable origin and staging, classification of tumors into a specific histopathologic type or grade is generally of relatively less value. In cases of clearly non-malignant tumors where it is difficult to determine the specific histopathologic type or grade, it is generally acceptable to conclude the evaluation and report it as such, unless the clinician specifically requests otherwise. For potentially malignant or high-risk tumors, typing and grading often still affects the management.

Additional slices

Additional slices are indicated in the following situations:

• Re-excision does not identify tumor cells in a clearly non-radical primary excision or biopsy.
• The most aggressive pattern is seen in the last available section, in which case more sections are indicated (from the same paraffin block if additional tissue is not available).

Reporting

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.

  See also: General notes on reporting

General notes

Further reading: Starting pathology (handbook) Learning pathology Emergency pathology Fixation Gross processing Evaluation: Suspected malignancies Immunohistochemistry Consultation Reporting Secrets

Main page

• Main page of Patholines