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7/8/16 Urinary bladder, biopsy: Non-invasive low grade papillary urothelial carcinoma. Muscularis propria (detrusor muscle) is not identified.

9/2/16 Urinary bladder, bladder tumor, transurethral resection: High grade papillary urothelial carcinoma. No definite invasion identified. Muscularis propria (detrusor muscle) is identified and not involved by tumor.

1/7/17 A\S\Bladder: Noninvasive low grade papillary urothelial carcinoma. Granulomatous cystitis, consistent with BCG (Bacillus Calmette-Guerin) treatment. Lamina propria is not involved with tumor. Detrusor muscle is not identified.

4/4/17 Dome: Papillary urothelial carcinoma, low grade. No evidence of invasion. Muscularis propria is not present.

Patient is clearly followed for at least a year but no further information until 19 months later, 11/14/18, when biopsy of lung indicates metastatic disease.

11/14/18 Lung, right lower lobe, mass, biopsy: Metastatic urothelial carcinoma. Immunohistochemical analysis results (CK7 positive, CK20 focally positive, P63 positive, GATA3 positive, TTF1 negative and NAPSIN-A negative) support the diagnosis

Rule M11 states: Abstract a single primary when there are urothelial carcinomas in multiple urinary organs, but neither the Rule nor the Notes describe the timing of these multiple urinary organ carcinomas. Timing requirements for other rules are clearly stated.

Does Rule M11 have a timing requirement or is it intended to apply to all urothelial carcinoma tumors regardless of timing (and not already qualifying for application of a previous M rule)?

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?

Glioblastoma multiforme is listed as a synonym for the preferred term glioblastoma, NOS (9440) per Table 3 Column 2. Therefore, it seems reasonable to assume that a diagnosis of glioblastoma, NOS would be a new primary if it followed a glial or astrocytic tumor. However, in general, the Solid Tumor Rules use the preferred terminology and/or indicate when a specific rule also includes any tumor diagnosed as a subtype/variant. Rule M6 does not explicitly include a diagnosis of glioblastoma, NOS or any of its subtypes/variants (e.g., glioblastoma IDH-mutant or gliosarcoma). Does Rule M6 apply to any diagnosis of glioblastoma, NOS and any of its synonyms or subtypes/variants?

The patient has one tumor each in the left parietal and left medial temporal lobe. The tumors were excised. The final diagnosis for the left parietal tumor is glioblastoma, IDH-wild type. he final diagnosis of the left medial temporal tumor is, at least anaplastic astrocytoma, WHO grade III; see comment. The comment states: There is a single focus of vascular hyperplasia, separate from neoplastic cells. No necrosis is identified. These findings on their own would warrant a diagnosis of anaplastic astrocytoma, WHO grade III. However, in the context of the patient's glioblastoma in the left parietal lobe, and imaging showing ring-enhancing lesions of the parietal and temporal lobes, this specimen is favored to be an un-sampled glioblastoma, WHO grade IV. The Solid Tumor Rules indicate we may no longer use terms like favor(s) to code the histology, leaving the final diagnosis as the priority source for coding histology per the Histology coding rules.

The tumor board review confirmed that, despite the anaplastic astrocytoma on pathology, they felt strongly that this is a multifocal glioblastoma and not an anaplastic astrocytoma. Both the pathologist's comment and the tumor board's assessment indicate this patient does not have two primaries. However, the Solid Tumor Rules do not give priority to the tumor board's assessment over the pathology, and registrars are not to use ambiguous terms to code histology thus leaving the two histologies to consider. Per the Solid Tumor Rules, one tumor that is glioblastoma and one tumor that is anaplastic astrocytoma are multiple primaries per M11 (Abstract multiple primaries when separate, non-contiguous tumors are on different rows in Table 3 in the Equivalent Terms and Definitions. Timing is irrelevant).

As a central registry, we cannot ask the pathologist or attending physician for clarification as suggested in Section 3 of the Malignant CNS and Peripheral Nerves Equivalent Terms and Definitions. We can only follow the current Solid Tumor Rules. In doing so, we would have to ignore both the pathologist's and tumor board's assessment that this patient has multifocal glioblastoma. Is there any concern that this will lead to over-reporting?

Is an M rule needed to address multiple tumors and Note 2 in Table 3? Does Note 2 in Table 3 apply when multiple tumors exist and one tumor contains only ductal carcinoma?

The M Rules currently confirm that a metaplastic carcinoma (whether it is involved with ductal or lobular) and a separate ductal carcinoma are separate primaries because these histologies are on different rows in Table 3 (separate primaries per M14). There is no specific rule regarding metaplastic carcinomas in the Multiple Tumors (M Rules) module, so presumably, the presence of a separate ductal carcinoma is not lumped into Note 2 in Table 3 for metaplastic carcinoma.

However, the note is confusing when there are multiple tumors involved because it appears to the registrars there are two options for coding the histology. To some registrars, the rules indicate it does not matter if the tumor is predominantly ductal carcinoma as long as some percentage of metaplastic carcinoma is present, code histology to metaplastic carcinoma. For other registrars, the presence of solely a ductal carcinoma in a second tumor is a separate primary from the separate metaplastic carcinoma.

The M rules and Note 2 need to clarify this issue to promote consistency.

This question was prompted from preparing SEER*Educate coding exercises. We will use the answer as a reference in the rationales.

Patient has a 1.7 cm encapsulated papillary carcinoma staged as pTis located 2 cm from the nipple and Paget disease of the nipple on mastectomy pathology.

There is no indication in Table 3: Specific Histologies, NOS/NST, and Subtypes/Variants that encapsulated papillary carcinoma is a subtype of ductal carcinoma. Rule M8 notes that if the histology of the underlying tumor is any histology OTHER THAN duct or subtypes of duct, one should continue through the rules. But if M9 applies to this case, then incidence reporting will be increased in comparison to prior years.

In the April and July 2019 updates to the Solid Tumor Rules, the term simultaneous and Note 1 indicating histologies must be the same behavior were removed from rule M10 (ductal and lobular are a single primary).

We would like to confirm that rule M10 is the correct rule to apply to this case. This case is an invasive diagnosis approximately 4.5 years after an in situ diagnosis, so it seems like M17 should apply (invasive tumor following an in situ tumor more than 60 days later are multiple primaries).

An invasive tumor following an in situ tumor more than 60 days later of the same histology is a new primary. Similarly, it seems like an invasive tumor following an in situ tumor more than 60 days later of different histologies should be a new primary.

The patient was never treated for the 2016 diagnosis, so the 2019 diagnosis is the same tumor that has progressed. Prior SINQ 20091096 for a similar case type cited multiple primaries per the 2007 Multiple Primaries/Histology Rules, Rule M8, the same rule as the current Solid Tumor rule M17, because this is to be reported as an incidence case.

However, it seems like Solid Tumor Rule M3 would apply because a single tumor is a single primary, and behavior of the 2016 primary would then be updated from /2 to /3. It is unclear how one would advance to the Multiple Tumors module and apply M17 because there is really only a single tumor in this case.

If the term discontinuous foci means separate tumors, then rule M14 would apply making these multiple reportable tumors.