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The WHO Blue Books do not include dedifferentiated carcinoma as a valid histology for the breast.  However, there is known to be progression of ductal carcinoma that is essentially dedifferentiation of an estrogen receptor, progesterone receptor, and HER2 breast carcinoma to a triple negative "dedifferentiated" carcinoma which it appears this patient has. Whether we should accession this as a separate 8020/3 primary per M14 is unclear and the Solid Tumor Manual does not address this scenario.

The resection pathology report final diagnosis indicates this is both mixed mucinous and non-mucinous with a lepidic predominant component. The pathologist notes this is “Lepidic: 75%. Acinar: 25%.”  The percentage of the mucinous component is not documented.

Rule H1, Note 1, states “When mucinous carcinoma is mixed with another histology, such as adenocarcinoma and mucinous carcinoma, code mucinous ONLY when mucinous is documented to be greater than 50% of the tumor.” While mixed invasive mucinous and non-mucinous carcinoma is included in Table 2 (Combination/Mixed Histology Codes) without a required percentage, it is unclear whether one should move past Rule H7 and use Rule H8 to code this combination histology code. Rule H7 would instruct one to code the histology to lepidic adenocarcinoma (adenocarcinoma, lepidic predominant) based on the percentage of the lepidic component in the tumor. However, this does not address the mixed mucinous and non-mucinous diagnosis. Which H Rule and histology apply to this case?

SINQs 20190083, 20180088, and 20130221 all indicate diagnoses of prostate adenocarcinoma, followed by a diagnosis of metastatic small cell carcinoma of the prostate are separate primaries because these are distinctly different histologies. Does this logic still apply for 2023 and later since Rule M4 was added to the Other Sites M Rules? Rule M4 states, “Abstract multiple primaries when the patient has a subsequent small cell carcinoma of the prostate more than 1 year following a diagnosis of acinar adenocarcinoma and/or subtype/variant of acinar adenocarcinoma of prostate.”

This patient has a 2018 diagnosis of prostate adenocarcinoma treated with radical prostatectomy, followed by a 2023 diagnosis of metastatic small cell carcinoma of the prostate diagnosed on a liver metastasis core biopsy. Rule M4 does not indicate whether it applies to subsequent biopsy confirmed metastatic tumor only. When a diagnosis of small cell carcinoma follows a diagnosis of prostatic adenocarcinoma, it is almost always confirmed in metastatic sites rather than in the primary site. Does the logic in the referenced SINQs above still apply for Rule M4?

Serous borderline tumor–micropapillary variant (8460/2, C569) was included in the ICD-O-3 Behavior Code/term updates effective 1/1/2018 but marked as Not Reportable for 2018.

There have been multiple additional updates to the ICD-O but no further clarification as to the reportability of this histology. ICD-O-3.2 currently lists serous borderline tumor, micropapillary variant (C569) as 8460/2 with no mention of reportability and no information provided in Includes/Excludes.

SINQ 20220032 instructs capturing this histology as reportable when diagnosed 1/1/2021 or later and occurring in the testis. The answer indicates this is reportable due to the /2 behavior code in ICD-O-3.2, but it does not specify that it is limited to specific sites.

Is serous borderline tumor, micropapillary variant reportable for ovary? If so, what dates apply? Is serous borderline tumor, micropapillary variant of the testis diagnosed after 1/1/2021 reportable?

Starting for cases diagnosed in 2024, the SPCSM manual no longer requires the data items for clinical and pathologic tumor size.  Instead, it appears to align with the CoC data item of Tumor Size Summary.  The two manuals contradict each other when it comes to coding tumor size summary for neoadjuvant chemotherapy (NAC) treated cancers.  

STORE states: "If neoadjuvant therapy followed by surgery, do not record the size from the pathologic specimen. Code the largest size of the tumor prior to neoadjuvant treatment; if unknown code size as 999."  

2024 SPCSM states "If neoadjuvant therapy followed by surgery, do not record the size from the pathologic specimen. Code the largest size of the tumor prior to neoadjuvant treatment; if unknown code size as 999." It continues to state     

 12. Assign code 000 when…. (a) no residual tumor is found…(i) Neoadjuvant therapy has been administered and the resection shows no residual tumor &

14. Assign code 999 when...(d) Neoadjuvant therapy has been administered and resection was performed. Do not use a post-neoadjuvant size to code pathologic tumor size; however, you may use the clinical tumor size if available

It seems that we will lose the value of the tumor size summary if we code 000 when NAC is administered and there is no residual disease. 

Example: Patient has a 90 mm triple positive breast tumor and is treated with neoadjuvant TCHP (docetaxel/carboplatin/ trastuzumab/pertuzumab). After completing neoadjuvant therapy, the patient has a mastectomy with no residual disease noted on the final pathology report. 

Using the 2024 SPCSM instructions, code 000 for Tumor Size Summary instead of 090 for the clinical tumor size of 90 mm tumor noted before NAC was administered. This has the potential to affect data analysis, research, and clinical trial accrual.

The SEER Manual seems to give somewhat conflicting instructions for clinical trial therapies under the Neoadjuvant Therapy data item. One section states that limited systemic therapy may occur in clinical trials to impact the biology of a cancer, but is not a full course of neoadjuvant therapy with the intent to impact extent of surgical resection or other outcomes (organ preservation, function or quality of life); do not code as neoadjuvant therapy for the purposes of this data item. Then another section states for purposes of this data item, the criteria for neoadjuvant therapy include that treatment must follow recommended guidelines for the type and duration of treatment for that particular cancer site and/or histology, and that neoadjuvant therapy may be given as part of a clinical trial.

For example, a patient was diagnosed with invasive ductal carcinoma of the breast, 6 cm in size; treatment planning conference recommended neoadjuvant chemotherapy. The patient elected to participate in a clinical trial and was assigned to a group given the antibody drug conjugate datopotamab deruxtecan (Dato-DXd) plus durvalumab for 12 weeks. There was no physician documentation of intent or expected outcomes, nor yC staging or statement of clinical response. Post-therapy imaging showed no residual mass, and post-therapy mastectomy path report showed only residual ductal carcinoma in situ, stating "Treatment Effect (after neoadjuvant): Residual Cancer Burden - pCR, In the breast - complete response."  The medical oncologist stated post-therapy stage was ypTis ypN0 cM0.

The trial drugs this patient were given do not appear to be approved or standard neoadjuvant/pre-operative drugs in SEER*Rx or NCCN guidelines for this type of cancer; however, the duration of treatment was fairly substantial, and although we don't have clear documentation from physicians as recommended in the SEER manual (which is usually not stated, in our experience), it seems like they may be considering it as neoadjuvant therapy. How should the Neoadjuvant Therapy data item be coded for cases like this? What is the best way to differentiate between clinical trial therapies that are "limited systemic exposure" (code 3) versus true neoadjuvant therapy (code 1)?

Appendix E1 in both the 2023 and 2024 SEER Program Coding and Staging Manual (SPCSM) lists these malignant spindle cell neoplasms, consistent with atypical fibroxanthoma, as reportable when other tumors have been ruled out with immunohistochemistry. This contradicts both SINQ 20190102 and the Solid Tumor Rules (STRs) general instructions indicating ambiguous terminology (e.g., “consistent with”) cannot be used to code the more specific histology when there is a NOS (malignant spindle cell neoplasm, 8004/3) and a more specific (malignant atypical fibroxanthoma, 8830/3) histology.

These tumors are typically diagnosed and treated in dermatology offices, so further chart review or confirmation by a physician is not possible for central registries.

As non-melanoma skin primaries are included in the Other Sites schema, and this schema was updated for cases diagnosed 2023 and later, which instruction applies to 2023+ diagnoses? Should these continue to be collected per Appendix E1 despite the conflict with the STR Manual and SINQ? If these are reportable, should the SINQ and STR Manual be updated to reflect this? Or should these be non-reportable per the STR Manual and SINQ?

Rule M15

Abstract a single primary when synchronous, separate/non-contiguous tumors are on the same row in Table 2 in the Equivalent Terms and Definitions.

Note: The same row means the tumors are

• The same histology (same four-digit ICD-O code) OR

• One is the preferred term (column 1) and the other is a synonym for the preferred term (column 2) OR

• A NOS (column 1/column 2) and the other is a subtype/variant of that NOS (column 3) OR

• A NOS histology in column 3 with an indented subtype/variant

Example: TURBT shows invasive papillary urothelial carcinoma 8130/3 and CIS/in situ urothelial carcinoma 8120/2. Abstract a single primary. Papillary urothelial carcinoma and urothelial carcinoma are on the same row in Table 3.