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March 2017 lung biopsy showing metastatic melanoma. Subsequent workup shows imaging with additional metastatic involvement of multiple bone sites but no primary tumor is identified. Chemotherapy is started in May 2017.

July 2017 biopsy of right lower quadrant mass has a final diagnosis of ganglioneuroblastoma and pathologist's comment states I believe that this may represent transdifferentiation of metastatic melanoma. Later, partial colectomy of transverse colon Gross Description indicates this was centered in the mesentery.

The physician stated the prior LUL adenosquamous carcinoma was PD-L1 negative and the LUL squamous cell carcinoma is PD-L1 positive and is calling it a new primary.

5/22-7/3/19 6000x30 IMRT Photons LUL lung Chemo refused Not a Surg candidate

10/01/2019 CT Chest: IMP: In comparison to CT chest 03/06/2019 and PET/CT 03/21/2019, left lingular mass has mildly decreased in size. Left apical anterior and posterior lung lesions more anterior lesion appears slightly increased in size, the other slight decreased in size, with adjacent areas of atelectasis and scarring.

06/23/2020 CT Chest: MP: In comparison to CT chest 10/1/2019, left lingular mass has increased in size concerning for increasing tumor with adjacent thicker focal pleural thickening involving the chest wall, concerning for possible chest wall invasion. Left apical anterior and posterior lung lesions appears more solid in appearance, representing known adeno CA, given that the appearance has changed, is concerning for residual tumor.

07/06/2020 PET: Hypermetabolic lingular mass and peripheral nodularity has increased in size and FDG avidity on the prior PET/CT. Left apical nodular opacity is difficult to separate from fairly uniform mild left apical pleural hypermetabolism which may be treatment related and/or neoplastic.

The Solid Tumor Rules indicate bladder tumors that are urothelial carcinoma (8120) and small cell carcinoma (8041) are separate primaries per Rule M13 (Abstract multiple primaries when separate/non-contiguous tumors are on different rows in Table 2). These are distinctly different histologies and, presumably, one would want to capture the small cell carcinoma (or small cell carcinoma component) as this has a worse prognosis.

However, if a subsequent bladder tumor is composed of invasive urothelial carcinoma and small cell neuroendocrine carcinoma, the histology is coded as 8045/3 per Rule H4, but this is not abstracted as a multiple primary. The only M Rule that applies is Rule M18 (Abstract a single primary when tumors do not meet any of the above criteria). The mixed histology code 8045 is not included in Table 2, so none of the histology-based M Rules apply. Is the subsequent mixed invasive urothelial and small cell carcinoma tumor (8045/3) the same primary as a previously diagnosed invasive urothelial carcinoma (8120/3) when these tumors are diagnosed within three years?

Acinar predominant adenocarcinoma measures at least 12 mm and involves wedge biopsy margins, while the lepidic predominant adenocarcinoma measures 11 mm and does not involve the margins of that separate specimen. Pathologist also notes, “CT findings of diffuse coarse reticular nodular opacity, these findings may represent pneumonic type adenocarcinoma/diffuse pulmonary involvement or intrapulmonary metastasis.  Both of these scenarios have the corresponding stages of pT4 (if thought to be ipsilateral) or M1a (if thought to also involve the contralateral lobe).”

Patient declined any further treatment and transitioned to hospice before expiring less than 1 month after wedge biopsies.

It is unclear if Rule M6 would apply to these two specimens with different subtypes since this scenario is not specifically addressed in the M rule definitions.

According to the Multiple Primaries/Histology Rules in place at the time of the 2016 diagnosis, verrucous carcinoma was listed as a specific type of squamous carcinoma (Chart 1). However, in the current Solid Tumor Rules, verrucous carcinoma is not listed in Table 4 (Tumors of Oral Cavity and Mobile Tongue) either as a specific histology or as a specific subtype/variant of squamous carcinoma. The only subtype/variant listed for these sites is acantholytic squamous cell carcinoma (8075).

Verrucous carcinoma is not listed in Table 4, making it unclear if it should be a different histology for these specified sites. However, verrucous carcinoma is listed as a specific subtype/variant of squamous carcinoma for other sites (e.g., Table 3).

The patient presented with a right chest wall nodule. The PET scan showed widespread disease: subcutaneous nodule/mass in the left scalp and right chest wall; large right paraspinal mass; soft tissue density likely a second early paraspinal mass at the right costovertebral junction; right paravertebral mass; and abnormal bony foci in the right humeral head, right iliac crest, right acetabulum and right femur. The physical exam showed 2 cm left supraclavicular lymphadenopathy and a firm 3 cm mass in the right chest wall. Lungs were clear. Abdomen showed no masses or ascites, and no palpable hepatosplenomegaly.

Chest wall nodule excisional biopsy pathology: Lymph node and adjacent soft tissue: Malignant lymphoma with components: 1. Diffuse large B-cell lymphoma (40%). 2. Follicular lymphoma, grade 3A (60%). Pathology report note states the diffuse large cell lymphoma is probably arising from the follicular center cell lymphoma.

Should this be a single primary? There is no mention of cutaneous lymphoma.

The patient was incidentally diagnosed with cancer on a prophylactic mastectomy, so there are no positive imaging findings to correlate the number of tumors/masses. The final diagnosis was invasive tubular carcinoma, and referred to the CAP Protocol. The CAP notes: However, it does not specify whether the single contiguous focus also includes the in situ component. The CAP goes on to note DCIS was present: The gross description does not provide any indication of either a single or multiple tumors/masses/lesions, though it was referred to as "Lesion 1" in the gross description with no indication of other lesions.

The format of the CAP Protocol frequently does not specify whether the DCIS is a separate measured tumor, or if it is a component of the invasive tumor. This makes it difficult to determine whether the DCIS should be a separate primary when the invasive tumor is not also a type of ductal carcinoma. Per both the 2007 MP/H and 2018 Solid Tumor Rules, an invasive tubular carcinoma and a ductal carcinoma in situ would be multiple primaries if they were multiple tumors. Should we default to Rule M1: Abstract a single primary when it is not possible to determine if there is a single or multiple tumors? Or should we assume these are separate tumors because they were both sized, the focality only described a single invasive tumor, and the tumors are not both ductal carcinomas?

Patient was diagnosed with T1 N0 M0 adenocarcinoma with prominent clear cell features [8310/3] in the LUL on 08/05/2010. The patient underwent a lobectomy only.

On 10/09/2012 the patient underwent an iliac bone biopsy showing non-small cell carcinoma with glandular and squamous features [8560/3]. Clinically, the physician is calling this stage IV adenosquamous carcinoma of lung origin involving lymph nodes, spleen and bones. There were no FDG avid pulmonary nodules found. There was no pathologic comparison to the prior lung tumor.

Should the 2012 diagnosis be a new primary because the histology is different from the 2010 diagnosis? Or should this be one primary because there appears to be only metastatic disease with no new primary lung tumor identified in 2012? The choice of one primary seems supported by the fact that the 2012 tumor showed glandular and squamous features, and the 2010 tumor also showed glandular and clear cell (NOS) features. The clear cell could have been a clear cell squamous cell carcinoma. The original tumor was not re-examined.

Should this be a new primary per the MP/H Rules (Other Sites, Rule M10) because the diagnoses were made more than one year apart? Or is the new disease metastasis? The pathologist did not compare the subsequent mass biopsies with the original pathology. Is a pathologist's comparison of slides the only criteria for determining recurrent disease? This case seems to fit the definition of metastatic disease rather than a recurrence, and therefore would not be a new primary.