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The case in question represents an adenocarcinoma with neuroendocrine differentiation that arises in the absence of androgen-deprivation therapy. A 2023 journal article states, “We show that amphicrine prostate cancer is a unique entity and differs in clinical and molecular features from high-grade neuroendocrine carcinomas of the prostate. Our study highlights the need to recognize AMPC as a unique molecularly defined subgroup of prostate cancer.”

Should we be coding this with histology 8140 (Adenocarcinoma, NOS) because we have no specific code for an amphicrine carcinoma? Should we code this as 8045 (Mixed small cell carcinoma) because this is possibly the only way to capture both the adenocarcinoma and neuroendocrine components in a patient without previous treatment?

Our concern about using histology code 8574 (Adenocarcinoma with neuroendocrine differentiation) is that, while a valid histology code, this might confound the data if researchers are trying to separate the truly treatment-related tumors from other histologies captured under 8574.

This patient does not have a previous diagnosis of prostate adenocarcinoma nor a previous history of androgen-deprivation therapy.

Does the logic in the Other Sites Solid Tumor Rules (STRs) noted in SINQ 20200052 still apply? This SINQ confirms a diagnosis of mixed prostatic adenocarcinoma and small cell neuroendocrine carcinoma is 8045. This matches the STRs instructions for Rule H21 and Table 2 (Mixed and Combination Codes), row 1. Row 1 indicates a mixed small cell carcinoma and adenocarcinoma is combined small cell carcinoma (8045). For a patient without previous treatment, is this the correct mixed histology code?

Note 1 states that this histology is treatment-related neuroendocrine prostatic carcinoma demonstrating complete neuroendocrine differentiation or partial neuroendocrine differentiation with adenocarcinoma after androgen-deprivation therapy (ADT). Conversely, Note 2 says to code 8574/3 only when there is no history of previous prostate adenocarcinoma or history of androgen-deprivation therapy.

The WHO Blue Book does confirm this is a treatment-related histology, so it seems we would only use this for an adenocarcinoma with neuroendocrine differentiation (or even possibly a mixed histology tumor with adenocarcinoma and small cell carcinoma components) if the patient had previous treatment.

If this histology is treatment-related, why would we use this code for a patient without a history of prostate adenocarcinoma or androgen-deprivation therapy? Should Note 2 be corrected?

Does this histology apply to a post-treatment diagnosis of mixed adenocarcinoma and small cell carcinoma? If yes, should this clarification be added?

We included this histology in SEER Workshop Case 12 and the histology coding accuracy was less than 40%. From emails we received, it is clear that registrars are unaware that the "somatic type malignancy" can vary but code 9084 applies when the diagnosis is teratoma WITH any non-germ cell tumor component. It may be helpful to add a definition for "teratoma with somatic-type malignancy" (9084) to the Solid Tumor Manual.

Patient had a hemithyroidectomy with the final diagnosis above. There does not appear to be an Other Sites H rule or table that addresses this combination of histologies for thyroid primaries.

There is an ICD-O histology code for papillary carcinoma, columnar cell (8344/3) as well as papillary carcinoma, encapsulated (8343/3). Per Rule H13, the terms “with features of” may be used to identify a subtype.

Considering these two subtypes, and knowing there is no specific histology code for this combination, is the first rule that applies H17 (code the numerically higher histology code)?

2016 Total thyroidectomy, Multifocal

-Dominant Tumor:  Right Lobe, Papillary thyroid carcinoma (8260/3)

-Tumors two through five:  Three tumors Papillary thyroid carcinoma (8260/3), and one tumor Papillary thyroid carcinoma, follicular variant (8340/3)

-An additional tumor: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (8343/2)

The left thyroid lobectomy/isthmusectomy returned a diagnosis of sclerosing mucoepidermoid carcinoma with eosinophina, 6.5 cm, replacing nearly the entire left lobe of the thyroid.

The patient has a completion thyroidectomy of the right lobe and returned the diagnosis of papillary thyroid carcinoma, 0.5 mm, in maximum dimension.

The endocrinologist describes it as "co-exsisting" and states the tumor is iodine non-avid.

Patient had a total abdominal hysterectomy-bilateral salpingo-oophorectomy performed in January 2023 with final diagnosis of myxoid and epithelioid leiomyosarcoma.

Diagnosis comment states: The tumor is 15 cm per report. It grows in nests and poorly formed interanastomosing trabeculae and cords that are separated by abundant myxoid background. The cells have an epithelioid morphology with eosinophilic cytoplasm, large nuclei, and very prominent nucleoli. The mitotic activity is overall low ranging from 1 to 3/10 HPFs.

Immunohistochemical stains performed at the outside hospital showed diffuse positivity for SMA, desmin, caldesmon, and PR. They are negative for CD10, claudin-4, calretinin, HBM45, MART1 (rare weakly positive cells), PANCK, and SOX10. This immunohistochemical profile supports a smooth muscle derivation of this neoplasm. As this tumor is extensively myxoid, diagnostic criteria differ from the spindle cell leiomyosarcoma.

Per Solid Tumor Rules Other Sites, Table 16: Uterine Corpus Histologies, Epithelioid Leiomyosarcoma (8891/3) and Myxoid Leiomyosarcoma (8896/3) are both subtypes of Sarcoma, NOS (8800/3).  Per Rule H21, use a combination code when there are multiple specific histologies AND the combination is listed in Table 2 OR there are coding instructions for the combination in the applicable histology Tables 3-21 OR you receive a combination code from Ask A SEER Registrar.  Since there is no combination listed in Table 2 and there is no instruction for the combination in Table 16, how should the histology be coded for this tumor?

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?