Evaluation of suspected malignancies

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Author: Mikael Häggström [note 1]
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.[1] 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

Benign[2] Malignant[2]
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.

Visually, tumors and other suspected malignancies can usually be classified into one of the following groups:

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.

Gland-like tumors

Typical features of adenocarcinomas on cytology (Pap stain). Vacuoles may be seen in both mucinous and serous tumors.

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 generally confined within their anatomic layers, that is, they are not invasive.
  • Adenocarcinomas, with the main criterion being invasiveness. Evaluate specifically by location when possible. Some specific locations included in this resource:

Squamoid tumors

These are more or less looking like a squamous-cell carcinoma:

Differential diagnoses depend on location, such as:

Spindle-cell tumors

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.

Undifferentiated tumor

An initial panel of cytokeratin (CK), S100, vimentin and LCA (CD45) can be used.[4]

No tumor

If a neoplasm has been ruled out for what clinically appeared like a tumor, seek a diagnosis that can be consistent with the clinical findings that caused the suspicion. If no explanation is found on the slides, generally take additional levels on the paraffin block, or more sections from any leftover tissue.

For example, for a breast biopsy of what appeared to look like a mass, and there is no neoplasia, look mainly for dense fibrosis or other fibrous changes, so that you can report it and thereby explain the finding, rather than merely writing "benign breast tissue".

Additional levels or slices

Additional material is 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).

Depending on availability and greatest suspicion, additional material is either acquired by taking addition step sections of remaining tissue in a paraffin block, or taking additional slices from the original specimen.

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:[1]

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.

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.

Reporting

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines. If a surgery produces a specimen with cancer, as well as re-excisions from certain directions, you should preferably give the closest distance to margins in each specimen, as well as the closest distance overall in a synoptic, for example:

A. (Specimen with most of the cancer)
  • (...)
  • Invasive carcinoma is present at inked medial margin (see specimen B for final medial margin), and is located 0.3 cm from the lateral margin.

B. (Re-excision in the direction of the medial margin)

  • (...)
  • Invasive carcinoma is located 0.5 cm from the new medial margin.

Synoptic report

  • (...)
  • Distance from invasive carcinoma to closest margin: 0.3 cm
  • Closest margin(s) to invasive carcinoma: Lateral

  See also: General notes on reporting


General notes edit

Further reading:

Notes

  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.

Main page

References

  1. 1.0 1.1 . Cancer staging. National Cancer Institute. Retrieved on 4 January 2013.
  2. 2.0 2.1 . General oncology. Amboss. Retrieved on 2020-01-29.
  3. Choi JH, Ro JY (2020). "Epithelioid Cutaneous Mesenchymal Neoplasms: A Practical Diagnostic Approach. ". Diagnostics (Basel) 10 (4). doi:10.3390/diagnostics10040233. PMID 32316685. PMC: 7236000. Archived from the original. . 
  4. Lin F, Liu H (2014). "Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. ". Arch Pathol Lab Med 138 (12): 1583-610. doi:10.5858/arpa.2014-0061-RA. PMID 25427040. Archived from the original. . 

Image sources