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There was a 3.5 cm invasive adenocarcinoma tumor in the pancreatic head. There were four separate, sized pancreatic neuroendocrine tumors measuring 0.9, 0.7, 0.5 and 0.2 cm in the pancreatic body. There are multiple tumors with distinctly different histologies. However, Table 11 (Pancreas Histologies) does not include any entries for neuroendocrine tumors of the pancreas (e.g., pancreatic NET, WHO grade 1, histology 8240). While it would seem Rule M19 should apply as they’re distinctly different histologies, because PanNETs are not included in Table 11, it is not clear which M Rule applies to these multiple tumors.

If Rule M19 does not apply, we are left with Rule M21 (Abstract a single primary when there are multiple tumors that do not meet any of the above criteria). Are these separate tumors with distinctly different histologies really a single primary? Pancreatic neuroendocrine tumors are not an uncommon histology, is there a reason these were not included in Table 11?

Treatment for estrogen receptor positive (ER+) breast cancer started with tamoxifen (non-steroidal estrogen subcategory) and switched to letrozole (non-steroidal aromatase inhibitor subcategory). Patient being treated with immunotherapy, Avastin (cytostatic agent-antiangiogenesis agent subcategory), and then changed to Atezolizumab (monoclonal antibody subcategory).

Is Atezolizumab a new course of therapy because it is a different subcategory?

The synoptic report calls this “Invasive adenocarcinoma with secondary Paget disease of anal mucosa and perianal skin.” The tumor size is listed as “2.1 x 1.7 x 0.7 cm, including associated advanced adenoma; size does not include the extent of the associated Paget disease, which extends for at least 2 cm distally.”  Clinically this is called an incidentally discovered Paget’s disease.

It is unclear if this is a collision tumor that should be abstracted as separate primaries, or if this is a single tumor with underlying Paget’s disease (similar to that described in Other Sites Rule H26). If this is a single rectal tumor, there does not appear to be an H rule for this scenario.

The patient has a history of ganglioglioma, WHO grade I, involving the deep right parietal lobe diagnosed on resection in 07/2012. Tumor recurrence in 2017 was treated with radiation.

The patient then had right temporal tumor biopsy and resection 06/2021 with final diagnosis of anaplastic glioneuronal tumor, BRAF p.V600E mutant, WHO Grade III. Pathologist notes that the tumor demonstrates a ganglioglioma with frequent mitoses and possible vascular proliferation. Subsequent consult findings support an anaplastic glioneuronal tumor, compatible with progression of the patient's ganglioglioma that is post-irradiation. However, the pleomorphic and epithelioid areas are also reminiscent of pleomorphic xanthoastrocytoma, which may occur in combination with ganglion cell components. There is no related SINQ to code this histology.

2021-Right pleural fluid:  Negative for carcinoma.

5/18/2021: Right iliac crest bone marrow core biopsy, aspirate smear, clot section and peripheral blood smear:  Hypercellular bone marrow, morphological findings are suspicious for a myeloproliferative neoplasm. Flow Cytometry: Slight immunophenotypic abnormalities of the myeloid cells. No abnormal B cell, T cell, or NK cell populations identified. Normal female karyotype. KARYOTYPE: 46,XX[20]. Negative for deletion of 13q14.3 (D13S319) by FISH. Negative for deletion of 13q34 (LAMP1) by FISH. Negative for hyperdiploidy involving chromosome 9 by FISH. Negative for t(9;22)(q34;q11.2) by FISH. Negative for deletion of the EGR1 gene on 5q31 by FISH. Negative for monosomy 5 by FISH. Negative for deletion of 7q31 by FISH. Negative for monosomy 7 by FISH. Negative for deletion of 20q12 by FISH. Negative for trisomy of chromosome 8 by FISH.

6/4/21-Left adrenal; biopsy: poorly-differentiated malignant neoplasm with extensive necrosis. Immunohistochemical stains show the neoplastic cells to be negative for CK7, TTF-1 and p63. Negative CK7 and TTF-1 would argue against a lung primary. Correlation with clinical and radiological findings is advised.

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Rule M4 was added to the Other Sites M Rules to address diagnoses of small cell carcinoma following prostate adenocarcinoma, but Rule M4 states the diagnoses must be greater than one year apart.

In this situation, the diagnoses were less than one year apart and one must continue through the M Rules. The next M Rule that applies Rule M19: “Abstract multiple primaries when separate/non-contiguous tumors are on multiple rows in Table 2-21 in the Equivalent Terms and Definitions. Timing is irrelevant.” If one were to STOP at the first rule that applies, one would stop at Rule M19 which confirms the prostatic adenocarcinoma and small cell carcinoma are separate primaries, regardless of timing. If these are not to be accessioned as multiple primaries, does an Exception need to be added to M19?

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?

Historically, multiple invasive ductal and lobular carcinomas diagnosed within 5 years were abstracted as a single primary. However, it is not clear if Rule M10 or M14 applies to this situation per the 2023 Solid Tumor Rules updates.

Rule M10 addresses multiple tumors of carcinoma of no special type (NST)/duct and lobular, but there is no timing criteria mentioned. Does M10 apply to cases diagnosed synchronously, or metachronously, or at least within 5 years? Should Rule M10 include a Note instructing registrars to accession a single primary for the scenario in question?

If timing matters for Rule M10, then the next rule that applies is M14. Rule M14 instructs one to abstract multiple primaries when separate/non-contiguous tumors are on different rows in Table 3, and carcinoma NST/duct and lobular carcinoma are on separate rows in Table 3.