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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.

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.

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.

The bone marrow biopsy proved bone marrow with blasts comprising 15-19%. Neither the pathologist nor the physician specifically diagnosed this as AML, calling this only high risk disease or early evolving AML prior to starting the patient on Vidaza.

No further information can be obtained from the pathologist or the physician for this case. Should this early evolving AML be accessioned as an additional primary per Rule M10, or is this the same MDS that is now high risk as the blast count is up to 19%, but has not yet reached the threshold of 20% blasts usually required for AML per the Hematopoietic and Lymphoid Neoplasm Database?

Malignant Central Nervous System (CNS) Rule M5 instructs us to abstract a single primary (as malignant) when a single tumor is originally diagnosed as non-malignant, the “First course treatment was active surveillance (no tumor resection),” and the subsequent resection pathology is malignant.

This patient’s first course of treatment was not active surveillance. While the patient did not have first course tumor resection, the tumor was treated with Cabergoline.

Should Rule M5 apply because there was no tumor resection? If so, should Rule M5 clearly state no tumor resection is the criteria (not active surveillance)?

SINQ 20230023 does indicate a PitNET diagnosis following a diagnosis of pituitary adenoma does not fall into standard rules, but in the previous SINQ the first course treatment was a partial resection.

It is unclear whether other types of treatment could result in a new malignant PitNET, following a previously treated non-malignant pituitary tumor.

Rectal polyp excised in June, 2012, found to have adenocarcinoma in situ in a tubulovillous adenoma. Additional colorectal biopsies in November; all were negative. Another rectal polyp removed in December 2012 showing a tubulovillous adenoma with focal carcinoma in situ. Then, in February, 2013 another rectal polyp removed. This was diagnosed as mod. diff. adenocarcinoma with mucinous features, infiltrating into submucosa, seen in a background of tubulovillous adenoma. Surgical margins free (mucin %=40%). Finally, in May, 2013, a low anterior resection with no residual adenocarcinoma.

This appears to be adenocarcinoma in multiple adenomatous polyps (8221/3), although the final path from May 2013 described one benign polyp and said, 'no other masses, suspicious lesions or polyps are identified.' Going through the MP/H rules, both M13 and M14 result in this being a single primary, and come before the rule about an invasive tumor following an in situ tumor more than 60 days later is a new primary. The original abstract was coded C209 and 8263/2. If this is a single primary, should it be changed to 8221 with a behavior code of 3? Is this scenario another example of when to change the original diagnosis based on subsequent information?

Scenario: Patient had a transurethral resection of the prostate on 8-29-19, positive for basal cell carcinoma with focal squamous differentiation involving approximately 50% of tissue (determined not to be mets by consult). On 11-14-19, the patient had a prostatectomy positive for residual basal cell carcinoma and a small focus of infiltrating prostatic adenocarcinoma. According to AJCC, 8th edition, page 724, basal cell carcinoma of the prostate is 8147/3 and we ignored the small focus of adenocarcinoma. The above scenario was reported as two primaries (8090/3 and 8140/3), but we are thinking it is one.

Disease History

2018 - Lymphomatoid papulosis (non-reportable)

2020 - Transform to CTCL (and called Mycosis Fungoides specifically) (CTCL/MF same primary)

2021 - Transform to CTCL with large cell transformation

7/25/17

Part A: Left breast at 8:00, 5 CFN: Specimen type: Stereotactic biopsy. Tumor type: Ductal carcinoma in situ (DCIS), cribriform type. Tumor size: The largest focus of DCIS measures 1 mm in greatest dimension as measured on the slide. Nuclear grade: 2 (Intermediate grade). Microcalcifications: Present. Other findings: Stromal fibrosis, microcalcification and fat necrosis.

11/1/17

A. Sentinel lymph node, left: One lymph node, negative for metastatic tumor on three levels of routine H\T\E and pan cytokeratin immunohistochemical stains.

B. Left breast: Procedure: Total mastectomy with skin and nipple. Specimen Laterality: Left. Lymph Node Sampling: Yes, portion A. Specimen Integrity: Intact. Histologic Type: Extensive ductal carcinoma in situ and one focus of Invasive ductal carcinoma with mucinous features. Histologic Grade (Nottingham Histologic Score): Glandular Differentiation: Score 3 Nuclear Grade: Score 2. Mitotic Count: Score 1. Total Nottingham score 6 (grade 2, moderately differentiated). Tumor Size: 3.3 x 2 mm (0.33 x 0.2 cm) measured on slide (B3). Tumor Site: Lower inner quadrant of left breast. Tumor Focality: Unifocal. Ductal Carcinoma In Situ (DCIS): Present, cribriform, solid and micropapillary types with focal necrosis and calcifications. Size of DCIS: Number of blocks examined: Thirty (30). Number of blocks with DCIS: Thirteen (13). Lobular Carcinoma In Situ (LCIS): Not identified, Lymphovascular Invasion: Present. Perineural Invasion: Not identified. Other Findings: Changes consistent with previous biopsy site. Cysts, foci of atypical ductal hyperplasia, focal ductal hyperplasia, adenosis, stromal fibrosis and microcalcifications. Skin (epidermis): Uninvolved. Nipple: Uninvolved. Margins: 1 mm from DCIS to the closest deep margin (slide B12). At least 10 mm (1 cm) from invasive carcinoma to deep margin. Estrogen receptor (ER, clone 1D5) by immunohistochemistry performed on this material: Positive (invasive and in situ carcinoma), high intensity, in greater than 95% of carcinoma cells. Progesterone receptor (PR, clone 16) by immunohistochemistry performed on this material: Positive (invasive and in situ carcinoma), moderate intensity in about 80% of the carcinoma cells. Her 2 by FISH performed on this material: Pending, an addendum to follow. Pathologic staging: pT1aN0(sn)MX (AJCC 7th edition). Dictated by: (Pathologist), MD Intradepartmental review.

The patient has a history of a minimally invasive endometrial adenocarcinoma that was low grade and confined to an endometrial polyp in 2001. The patient underwent a total abdominal hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO) that entirely removed the tumor at that time.

Almost 18 years later, the patient had a left inguinal mass excision that was, Carcinoma of gynecologic origin, consistent with clear cell carcinoma. No other disease was found, the physician never indicated whether this was felt to be metastatic from the previous, low grade adenocarcinoma or not. It was only noted as, an unusual malignancy of the left lower quadrant and inguinal region of gynecologic origin. No further information was available in the medical record or from the physician on follow-up.

Although neither the Solid Tumor Rules nor the MPH Rules (still in use for the Other Sites schema) apply to metastasis, given the differences in histology and behavior of these two tumors (i.e., minimally invasive, low grade disease diagnosed in 2001 vs. higher grade, more aggressive tumor in 2019) should the current clear cell carcinoma of GYN origin really be the same primary as the 2001 endometrial adenocarcinoma?