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History provided by the oncologist

Right neck mass since 2019; 04/07/20, initial biopsy p16-negative SCC, delay of treatment due to patient preference, agreed to biopsy of tonsil and work-up August 2022; right tonsil biopsy: p16-positive, G2 SCC, nodal mass at that time >6 cm with extensive extranodal extension, Stage III (cT2, cN3, cM0, p16-positive); based on this history, was staged as a tonsil primary and p16-positive.

Patient details

1. March 2020, CT neck and chest revealed a 0.5 x 2.7 x 2.3 cm low-density necrotic nodal mass at right neck level 2 suspicious for metastatic disease.  There was a slight asymmetric increased size of the right palatine tonsil.  There are a few sub-4 mm pulmonary nodules which are nonspecific.

2.  April 7, 2020, FNA of right neck mass with pathology revealed p16-negative SCC   

3.  April 20, 2020, PET/CT revealed 3 x 2 cm right-sided level 2 node with FDG avidity  

4.  May 5, 2020, flexible laryngoscopy showed no obvious primary lesion   

5.  May 2020, after evaluation by a medical oncology, patient declined any treatment  

6.  June 17, 2022, return visit in medical oncology after PET/CT demonstrates significant progression in the neck; patient definitively declines chemo, but would like surgical opinion.  Now has more rapidly progressive disease with skin breakdown and weeping from malignant lesion right neck.  

7.  June 22, 2022, radiation oncology consultation   

8.  July 15, 2022, tonsil biopsy: Invasive squamous cell carcinoma, moderately differentiated with LVI, p16-positive  

9.  Patient now agreeing to treatment with radiation: Tooth extractions 8/30/2022, radiation planning 9/14/2022  

10.  Patient consulted with cancer specialist who explained surgery is not recommended given level of extranodal extension and risk of seventh cranial nerve paralysis and fistula formation with surgical excision and who recommended chemoradiation

11.  September 9, 2022, patient presented for radiation CT simulation/treatment planning and informs treatment team. Patient declined/refuses concurrent chemotherapy despite recommendations from two cancer institutions.

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.

Colon, Rectosigmoid, and Rectum Multiple Primary Rule M7 states, Abstract multiple primaries when a subsequent tumor arises at the anastomotic site AND the subsequent tumor arises in the mucosa.

We identified tumors at the anastomotic site of previous colon primaries with no mention of mucosa in any of the available documentation. Are there any other indicators that would imply a tumor arising in the mucosa, or do we need this specific statement to apply rule M7?

Example: Patient has a history of invasive ascending colon adenocarcinoma diagnosed in October 2017 status post hemicolectomy followed by adjuvant chemo. There is no documentation of disease until August 2019 colonoscopy which shows a mass in the ileocolic anastomosis. Biopsy of the anastomotic site is positive for adenocarcinoma consistent with recurrence of the patient's colonic adenocarcinoma. There is no mention of mucosa found on the pathology report.

Patient was initially diagnosed with a right lower lobe (RLL) lung adenocarcinoma in 2014 followed by subsequent right upper lobe (RUL) lung adenocarcinoma in 2016 (single primary). Both were treated with radiation and the nodules were seen as stable on surveillance. There was subsequent growth in the RUL nodule in 2019 and RLL nodule in 2020 as well as a new right middle lobe (RML) nodule in 2020. All left sided nodules were noted to be stable and/or ground glass opacities.

There was no documented diagnosis of malignancy in the left lung until June 2020 when the physician noted that if there was a response in the left lung to systemic treatment, then this was probably multifocal AIS. However, only one tumor in the left lung responded to treatment.

While it seems somewhat unlikely that only a single AIS in the contralateral lung should be metastasis from the right lung malignancy, it is difficult to apply the multiple tumors rules to this case.

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.

Does ductal carcinoma with tubular features qualify for Breast MP/H Rule H28? Or, is it more appropriate to strictly follow Table 2 (not a type of ductal tumor) and apply Rule H29, thus losing the lobular component?

Since the peripheral nerves are included in the Malignant CNS schema of the Solid Tumor Rules, neither the differences in subsite nor timing indicate these are separate primaries (Rule M10 indicates a single primary). However, these are separate MPNSTs in different sites and the tumors are not stated to be metastasis. Additionally, these are treated as separate primaries by the managing physician.

While the malignant CNS tumors do not take timing into account, is this correct for these peripheral nerve tumors that are often treated similarly to soft tissue tumors? Should Rule M8 be updated to include tumors in different peripheral nerve subsites?

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.

11/18/2019 Left 1st Digit/Thumb Biopsy: Atypical Melanocytic Proliferation consistent with Early Acral Lentiginous Melanoma in situ. Margins Positive. (Not a reportable diagnosis for 2019.)

12/5/2019 Left 1st Digit Shave Biopsies: Malignant Melanoma in situ. Margins Positive.

1/15/2020 Started Aldara (treatment plan: use for ~3 months then Mohs/excision, but due to COVID could not get resection until 7/2020).

7/29/2020 Left Thumb Excision: Residual Melanoma in situ. Margins Positive. Treatment Plan: re-excision.

8/6/2020 Left Thumb Re-Excision: Atypical Lentiginous Melanocytic Proliferation at the 12-2 margin may represent the advancing edge of melanoma in situ. (8/19/2020 Plan to treat the 12-2 margin as positive with in situ; plan for re-excision).

8/20/2020 Left Thumb Re-Excision & Left Nail Plate Excision: Malignant Acral Lentiginous Melanoma with extensive melanoma in situ. Breslow 1.3mm. Margins Positive. Nail plate & bed epithelium with hemorrhage and a mild increase in melanocyte density likely represent melanoma in situ.

9/4/2020 Left thumb partial amputation & Left axillary Sentinel Lymph Node Excision: Residual Malignant Melanoma in situ. 0/3 sentinel nodes positive.

The Hematopoietic and Lymphoid Neoplasms Database (Heme DB) definition for systemic mastocytosis with an associated hematological neoplasm (SM-AHN, 9741/3) states SM-AHN is a variant of systemic mastocytosis that arises with a myeloid disease of non-mast cell lineage (e.g., MDS, MPN, etc.) and that,

However, SINQ 20130172 conflicts with the Heme DB stating the systemic mastocytosis and the associated hematological neoplasm are a single primary coded to a single histology (9741/3) per Rule M2.