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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?

Cytology is not listed in the Priority Order for Using Documentation to Identify Histology (Histology Coding Rules) in the Head and Neck schema. Other schemas do include cytology in the hierarchy below tissue from a biopsy or resection. Cytology is often less specific than histology, so one would expect cytology to be listed below tissue in this hierarchy. Was this an oversight? Or would cytology be equivalent to histology if it provided the most specific histology for the case?

Table 6 (Tumors of the Oropharynx, Base of Tongue, Tonsils, Adenoids) in the Head and Neck Equivalent Terms and Definitions lists both squamous cell carcinoma HPV-positive and squamous cell carcinoma HPV-negative as subtypes/variants of squamous cell carcinoma (the NOS histology, 8070). Squamous cell carcinoma HPV-positive and squamous cell carcinoma HPV-negative are also listed in the 2018 ICD-O-3 update table.

Previous clarification from the standard setters regarding the 2018 ICD-O-3 Update table indicated that histology codes 8085 and 8086 (HPV-positive and HPV-negative squamous cell carcinoma, respectively) included p16+ and p16- squamous cell carcinoma, respectively. Presumably, this clarification was made because p16 is a surrogate marker for HPV, and capturing whether a tumor is HPV-related or not has implications for staging for 2018 and later diagnoses. However, this clarification was not added to the 2018 ICD-O-3 Update table via errata, nor do the Head and Neck Equivalent Terms and Definitions or Histology Coding Rules address this.

Is a diagnosis of p16-positive squamous cell carcinoma equivalent to a diagnosis of squamous cell carcinoma HPV-positive (8085)? If so, will this clarification be added to the Head and Neck Solid Tumor Rules?

Patient had a breast excision that proved a single tumor with no evidence of invasive carcinoma. The final diagnosis stated: Size (extent) of EPC DCIS: Spanning approximately 1.3 cm. The pathologist did not describe separate foci of DCIS; only one tumor comprised of both encapsulated papillary carcinoma and DCIS. The encapsulated papillary carcinoma was not described as invasive. The pathology noted: This case is best classified as EPC conventional DCIS. No conventional stromal invasion is identified. Solid Tumor Rule M2 confirms a single tumor is a single primary.

However, there does not appear to be an H Rule that instructs how to code histology. The Single Tumor: In Situ Only module, has only three H Rules and none of them apply to this case. The patient does not have Paget disease (H1), does not have a single histology (H2, there are multiple histologies present as DCIS and EPC are listed on different rows in Table 3) and does not have DCIS and LCIS (H3). How does one arrive at the correct histology for this case?

The right breast ultrasound shows a 1.4 cm mass at 8 o'clock and a separate mass .6 cm at 7 o'clock (site code for both C50.5). Pathology report: Right 8 o'clock core needle biopsy fragments of intracystic noninvasive papillary carcinoma (8504/2), right 7 o'clock core needle biopsy fragments of intracystic noninvasive papillary carcinoma (8504/2). Then, another facility performs a right breast lumpectomy (operative note not available). Outside Facility: Right breast lumpectomy pathology shows invasive ductal carcinoma .6cm (8500/3) multifocal DCIS .5cm greatest dimension tumor site right breast NOS.

Should we use Rule M12-Abstract multiple primaries when separate/non-contiguous tumors are on different rows in Table 3 in the Equivalent Terms and Definitions. Timing is irrelevant. Note: Each row in the table is a distinctly different histology. So would this be two primaries C50.5 (8504/2) and C50.9 (8500/3)?

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 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?

The patient has a history of prostate adenocarcinoma with lymph node metastases, status post prostatectomy and treatment by Lupron in 2014. The most recent prostate serum antigen measurement (April 2018) was normal. CT scan of the abdomen and pelvis revealed new hypodense liver lesions, a slightly enlarging lung right lower lobe nodule, and enlarging lobular mass in the prostatectomy bed. The core liver biopsy contains areas of metastatic tumor with a differential diagnosis on pathology of high-grade neuroendocrine carcinoma of the prostate (small cell type), which may have been seen in association with prostate adenocarcinoma, or metastatic small cell carcinoma of a different site.

Clinically, the physician impression is that this represents metastatic castration-resistant prostate cancer. The Solid Tumor Rules note that the Multiple Primary Rules are not used for tumor(s) described as metastases. However, SINQ 20130221 indicates that, at least historically, these would have been accessioned as multiple primaries (histology 8140 & 8041 per Rule M10). Does the previous SINQ note still apply to these types of cases, and if so how would one know to move beyond the initial note indicating metastases are not new primaries?