Baylor University Medical Center Proceedings July 2017 - 317

of the scalp tumor. A few weeks after surgery, the patient died
from non-cancer-related reasons.

Figure 1. The patient's tumor and its histology. (a) Tumor on scalp that did not
respond to endocrine or cytotoxic chemotherapy. (b) Section of tumor from the
outmost part of the tumor staining positive for the estrogen receptor (100×
magnification). (c) Section of tumor from the innermost part of the tumor staining
positive for melanoma cocktail (100× magnification).the core biopsy.

July 2017

DISCUSSION
Our patient presented with not one, but two cancers. While
uncommon, two or more cancers can occur simultaneously,
deﬁned as multiple primary malignant neoplasms (MPMN).
Studies show that up to 11.7% of cancer patients can present
with MPMN (1). There are two types: metachronous, diagnosed
>6 months apart, and synchronous, diagnosed <6 months apart.
Our patient had synchronous cancers.
There are many cases of MPMNs; most involve patients with
metachronous cancers. Women with mutations in the BRCA2
gene appear to have a greater risk for developing cutaneous and
ocular melanoma (2-5). However, there is also an increased
relative risk of developing a melanoma after radiotherapy for
women with breast cancer (6, 7). The prevalence of breast cancer
as a secondary malignancy in melanoma patients was the third
most common cause of a secondary malignancy (7). Thus, it
appears there is a relationship between breast cancer and melanoma as primary and secondary cancers in MPMNs.
In relation to our patient's case, several examples of invasive
lobular breast cancer occurring simultaneously with melanoma
have been reported. One case study documented a patient with
multiple sclerosis who presented with six metachronous primary malignancies over a 4-year period, including a double
melanoma as well as a lobular invasive breast carcinoma (8).
The authors investigated speciﬁc gene alterations that may predispose a patient to develop multiple malignancies and found
the breast carcinoma and melanomas in their patient shared
alterations in two tumor suppressor genes, PTEN and P53, as
well as an insertion in codon 4 of the HRAS gene resulting in a
frame shift mutation (8). These changes could be instrumental
in causing the formation of multiple cancers. Other genetic
alterations could result in synchronous primary breast cancer
and melanoma seen in our patient.
An association between breast cancer and melanoma was
shown in patients with strong familial cancer lineage (9, 10). In
families with a high-risk genetic CDKN2A gene mutation for
melanoma, 6 of 9 had at least one family member with multiple
primary melanomas along with a high frequency of breast and
pancreas cancers. Interestingly, in the families with breast cancer,
there was a greater frequency of multiple melanomas (11). In
another study of 82 patients with both melanoma and breast
cancer, 12 patients had germline mutations in a single or various combinations of the BRCA1, BRCA2, TP53, or CDKN2A
genes (12). These rare cases indicate that germline mutations
may play a role in the formation of the two cancers.
In our patient, it is unclear what gene alteration may have
driven her cancers, as her tumors were not sequenced. Clinicians
need to keep an open mind in diagnosing tumor etiologies, especially with new molecular techniques and targeted therapies.
The principle of Occam's razor states that the simplest explanation, with the fewest assumptions, is usually correct. But, in this
case, the simplest explanation was not correct. The humbling
discovery of a second malignancy highlights the importance of

Two cancers in one

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Table of Contents for the Digital Edition of Baylor University Medical Center Proceedings July 2017