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The SEER SS (SSS) 2000 Manual indicates satellite nodules (NOS or less than/equal to 2cm from primary tumor) are regional by direct extension (code 2) and in-transit metastasis (satellite nodules greater than 2 cm from primary tumor) are coded as involvement of regional lymph nodes (code 3). However, CSv0205 indicates mapping for satellite nodules/in transit metastasis (coded in CS LN) was changed to Regional, NOS (code 5). There are no definitions listed for code 5 in the SSS 2000 Manual.

Our staff independently code SSS 2000. Should we code the existence of satellite nodules and in transit metastases according to the current definitions in the SSS 2000 Manual or using the mapping information from CSv0205?

The SEER*Rx Database lists Sirolimus as an ancillary agent under the Category section, but as an mTOR inhibitor under the Subcategory. The Remarks section indicates Sirolimus (AKA Rapamycin) is an immunosuppressant, but is also a type of serine/threonine kinase inhibitor. Other types of kinase inhibitors (including Temsirolimus) are types of Chemotherapy. Although the Coding section states this drug should not be coded, Primary Sites (NSCLC and glioblastoma) are listed for this drug.

The SEER*Rx Database page for this drug is confusing. Please address the following.

1) Should Sirolimus not be coded when it is being given as a kinase inhibitor or an immunosuppressant?

2) If Sirolimus is ever treatment, should it be coded only for the primary sites listed?

3) If Sirolimus is given as part of a non-blind clinical trial for another site other than NSCLC or glioblastoma, should the Other Therapy field be coded to 2 [experimental - other treatment]?

The SEER*Rx Database, Prednisone Primary Site indicates "Prednisone is used to treat multiple sites and histologies." The Remarks information states, "Prednisone may be coded as treatment (hormonal) for all sites and histologies. It is most often used as part of a drug regimen." While it is clear that Prednisone is coded as hormone therapy when administered as part of a drug regimen like CHOP, how is Prednisone coded when given outside of a drug regimen? Also, how is Prednisone coded for cancer-directed treatment of a metastatic lung primary? The NCI's PDQ does not list hormone therapy as cancer-directed treatment for a Stage IV lung adenocarcinoma.

In our specific case, Prednisone was started just after diagnosis, and before the completion of work-up proving distant metastasis. Often, Prednisone (or another hormone agent) is given as an ancillary treatment for the symptoms associated with the malignancy, and not as cancer-directed treatment.

The Single Versus Subsequent Primaries of Lymphatic and Hematopoietic Diseases table indicates they are most likely "D" different disease processes. As any low grade lymphoma can transform, we suspect this represents a transformation (the clinician is regarding this as transformed).

How many primary/ies should be coded?

And, how?

The Solid Tumor histology coding guideline #3 for Lung states that an ambiguous histology can only be coded over an NOS when a physician clinically confirms it or the patient receives treatment based on the ambiguous histology; similar instructions exist in rules H3 and H12.  We are in a central registry and don't typically have access to physician notes or treatment plans; unfortunately our hospital abstracts rarely document physician confirmation of ambiguous histology and we are uncertain if we should accept their coding of the more specific histology, assuming they did find clinical confirmation that was not documented.  If not, our understanding of the Solid Tumor rules is that the histology in such a case would have to be coded as malignancy NOS (8000/3) per the non-ambiguous final diagnosis, and that we cannot use the more specific but ambiguous squamous cell carcinoma since we don't have definite clinical confirmation.  We also have a fair number of cytology-only lung cases without any hospital information to clinically confirm an ambiguous histology.

The Solid Tumor Rules indicate bladder tumors that are urothelial carcinoma (8120) and small cell carcinoma (8041) are separate primaries per Rule M13 (Abstract multiple primaries when separate/non-contiguous tumors are on different rows in Table 2). These are distinctly different histologies and, presumably, one would want to capture the small cell carcinoma (or small cell carcinoma component) as this has a worse prognosis.

However, if a subsequent bladder tumor is composed of invasive urothelial carcinoma and small cell neuroendocrine carcinoma, the histology is coded as 8045/3 per Rule H4, but this is not abstracted as a multiple primary. The only M Rule that applies is Rule M18 (Abstract a single primary when tumors do not meet any of the above criteria). The mixed histology code 8045 is not included in Table 2, so none of the histology-based M Rules apply. Is the subsequent mixed invasive urothelial and small cell carcinoma tumor (8045/3) the same primary as a previously diagnosed invasive urothelial carcinoma (8120/3) when these tumors are diagnosed within three years?

The Solid Tumor Rules indicate p16 is a valid test to determine HPV status and can be used to code HPV-associated/-independent.

In this case, we do not know whether the HR-HPV test was done on cytologically malignant cells, or on benign cervical cells. It may be impossible to tell unless 100% of the cytology specimen is malignant, but we will not have access to that information. Also, HR-HPV testing is routine on Pap smears, so this testing does not mean the tumor cells specifically harbor HPV.

The Solid Tumor Rules instruct us not to use differentiation for coding histology unless it is specifically listed in the table. The terminology non-small cell carcinoma with neuroendocrine differentiation is not in lung histology Table 2.

However, SINQ 20150033, prior to Solid Tumor rules, indicates this diagnosis should be coded to 8574 (adenocarcinoma/carcinoma with neuroendocrine differentiation).

This presentation appears to represent distinctly different histologies. However, because the 2018 histology diagnosis is not in the table and the prior SINQ appears to disagree with current instruction, it is not clear how to apply the M rules to this case. The outcome of the histology coding will affect the number of primaries reported in this case.

The Solid Tumor Rules state that for cases diagnosed in 2022 and forward, p16 testing CAN be used to assign histology code 8085 (squamous cell carcinoma, HPV positive). The rules also state that for cases diagnosed prior to 1/1/2022, code 8085 MUST be based on ISH testing and not p16. ISH testing is not specifically addressed for 2022+ cases, but are we correct in assuming it can still be used as the basis for 8085?

Multiple CAnswer Forum posts and the AJCC 8th edition Head and Neck staging webinar indicate that the correct chapter/registry staging schema in this situation is determined ONLY by p16 results - not ISH testing, and therefore the Schema Discriminator 2 SSDI should be coded as 1 – p16 negative, regardless of ISH results.

While we understand that histology codes should not be changed based on staging criteria, there is a SEER/NAACCR edit, “Schema Discriminator 2, Head and Neck, Histology (NAACCR)” tag number N6802, that will not allow coding 8085 if Schema Discriminator 2 is coded as 1 (p16 negative). The edit does seem to be correctly enforcing the AJCC guidelines for choosing the staging schema, based on the sources noted above. Do the Solid Tumor or Site-Specific Data Items (SSDI) guidelines need to be modified for this situation?

The STR states that p16 can be used to code HPV-associated and HPV-independent histologies for selected sites depending on diagnosis year but contains no instructions about how to interpret p16 staining results on pathology reports. These are often stated in various ways in our area, depending on the pathology lab and different pathologists. The SSDI Manual and SEER Coding and Staging Manual each have some instructions and code definitions for p16, including:

- Code 0 for p16 expression of weak intensity or limited distribution

- Code 0: p16 Negative; Nonreactive

- Code 1: p16 Positive; Diffuse, Strong reactivity

- IHC for p16 expression is a surrogate marker for HPV infection

Example: 2023 squamous cell carcinoma of the vulva, partial vulvectomy; pathology states vulvar intraepithelial neoplasia-3, p16 immunohistochemistry demonstrates block-like expression, which supports the diagnosis. The next path report states invasive squamous cell carcinoma, stain for p16 is strong and diffuse in the lesion, supporting the above diagnosis. Neither path report specifically states "HPV-related," so are p16 "expression" and "strong and diffuse" staining enough to code the histology as 8085/3 for this case?