RAPACON, MARK GIANE DAVE V.

26 April, 2020
SURG 1 UST-FMS D2022

SURGICAL ONCOLOGY CASE

HPI: 29/F, premenopausal, previously diagnosed to have benign phyllodes tumor on the right breast
status post wide excision (Aug 2017), presented with a gradually enlarging breast mass on the left.
With no other associated symptoms.
PSHx: nonsmoker, non-alcoholic
FHx: Brother died of Kidney cancer (42y/o); Sister (36 y/o) diagnosed with invasive breast cancer;
She has 2 more siblings aged 32 (Female) and 38 (Male) who are currently asymptomatic
Pertinent PE: 3x4 cm, firm, round mass with well defined border, movable and non-tender located
at the outer quadrant of the left breast; No palpable supraclavicular and axillary lymph nodes

QUESTIONS:
1. What is your initial impression?
There is a possible recurrence of the phyllodes tumor because of her underlying history.
Malignancy could occur in 25% of the cases in women at risk of breast CA due to the presence of
phyllodes tumor. Thus, further testing is needed to determine malignant subtype.
2. How will you establish your diagnosis? What diagnostic tests or procedures will you do?
Diagnosing phyllodes tumors usually involves a combination of steps:
• A physical examination of the breasts. The physician may be able to feel the lump in the
breast, or the patient during a breast self-exam.
• A mammogram to obtain X-ray images of the breast and locate the tumor. On a
mammogram, a phyllodes tumor appears as a large round or oval mass with well-defined
edges. Sometimes the tumor might look like it has rounded lobes inside it. Calcifications can
show up as well. Calcifications are tiny flecks of calcium — like grains of salt — in the soft
tissue of the breast.
• Ultrasound to obtain sound-wave images of the breast to determine if the tumor is fluid-
filled or solid.. The images form as the sound waves are "echoed back" by the tissue. On
ultrasound, phyllodes tumors look like well-defined masses with some cysts inside of them.
• MRI to obtain additional images of the tumor and help in planning surgery.
• Biopsy to take samples of the tumor for examination under a microscope.
o Core needle biopsy (CNB), which uses a special hollow needle to take samples of the
tumor through the skin. The smaller tissue samples taken during core needle biopsy
may not be enough to confirm that a lump is a phyllodes tumor.
o Excisional biopsy, which removes the entire tumor. Some experts believe it is better
to use excisional biopsy if a phyllodes tumor is suspected. Examining the whole tumor
is often necessary to make the right diagnosis.
3. Explain the concept of tumorigenesis.
Tumorigenesis is the process of initiating and promoting the development of a tumor that
may progress beyond the limits of an organ or tissue. This multistep process involves acquisition of
genetic, epigenetic, and metabolic alterations often advantageous for tumor cells
Initiation involves the alteration, change, or mutation of genes arising spontaneously or
induced by exposure to a carcinogenic agent. Genetic alterations through gain of function mutations
of oncogenes or loss of function mutations of tumor-suppressor genes can result in dysregulation of
biochemical signaling pathways associated with cellular proliferation, survival, and differentiation,
which can be influenced by a number of factors, including the rate and type of carcinogenic
metabolism and the response of the DNA repair function. Second, the promotion stage is considered
to be a relatively lengthy and reversible process in which actively proliferating preneoplastic cells
accumulate. A tumor may arise from a single clone or from a large cell population which has
undergone the same initiating genetic event, making normal-appearing cells susceptible to an
increased malignant potential—field effect. Within this period, the process can be altered by
chemopreventive agents and affect growth rates. Progression is the phase between a premalignant
lesion and the development of invasive cancer. Progression is the final stage of neoplastic
transformation, where genetic and phenotypic changes and cell proliferation occur. This involves a
fast increase in the tumor size, where the cells may undergo further mutations with invasive and
metastatic potential. Chemopreventive agents should be able to preferentially act within the
initiation and promotion processes of carcinogenesis. Metastasis involves the spread of cancer cells
from the primary site to other parts of the body through the bloodstream or the lymph system.
Chemopreventive agents are known to inhibit angiogenesis and invasion of primary tumors, and thus
could be utilized to inhibit the metastasis of cancer.
4. What are the different hereditary cancer syndromes and associated genetic mutations? Which is
present in this case?

Li-Fraumeni Syndrome (LFS) is present in the case due to a defect in the p53 tumor-suppressor
gene. The following is a suggestive diagnostic criteria for LFS:
• 2015 Chompret criteria (~30% will have a germline TP53 pathogenic variant):
o A proband with a tumor belonging to the LFS tumor spectrum (e.g., premenopausal
breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system (CNS)
tumor, adrenocortical carcinoma) before age 46 years AND at least one first-
or second-degree relative with an LFS tumor (except breast cancer if the proband
has breast cancer) before age 56 years or with multiple tumors; OR
o A proband with multiple tumors (except multiple breast tumors), two of which
belong to the LFS tumor spectrum and the first of which occurred before age 46
years; OR

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 o A proband with adrenocortical carcinoma, choroid plexus tumor, or
rhabdomyosarcoma of embryonal anaplastic subtype, irrespective of family
history; OR
o A female proband with breast cancer before age 31 years.
• Hypodiploid acute lymphoblastic leukemia (ALL) diagnosed in a proband <age 21 years
(~50% will have a germline TP53 pathogenic variant)
• Somatic tumor tissue testing identifies one of the following:
o A TP53 pathogenic variant with an allele frequency of ~50% or >50%
o Absent or decreased staining of p53 by immunohistochemistry
5. Explain how a defect in this gene will lead to malignancy.
The gene p53 is a nuclear transcription factor and transactivates numerous target genes
involved in the induction of cell cycle arrest and/or apoptosis. Under normal conditions, p53 is
expressed at an extremely low level as a functionally latent form. Extensive mutation searches
demonstrated that over 50% of human cancers carry the loss of function mutations in p53 gene. Upon
DNA damage, p53 is induced to accumulate in cell nucleus through post-translational modifications
such as phosphorylation and acetylation. These chemical modifications convert p53 from a latent to
an active form, which might be due to the dissociation of MDM2 from p53—MDM2 is the major
regulator of p53 which can trigger the degradation of the gene by the ubiquitin system. Functionally
active p53 transactivates an appropriate set of its target genes to induce cell cycle arrest and/or
apoptosis, which is dependent on the extent and types of DNA damage. p53-mediated cell cycle arrest
allows cells to repair damaged DNA. When DNA repair is complete, cells re-enter the normal cell
cycle. In contrast, when cells have serious DNA damage, p53 exerts its pro-apoptotic function to
eliminate cells with serious DNA damage and thereby inhibit the transfer of damaged DNA to
daughter cells. Thus, p53 has an ability to maintain genomic integrity. Such mutation in p53 can lead
to a continuous and unregulated proliferation and its transmission to the daughter cells, hence,
malignancy.
6. Will this patient or her family benefit from genetic testing?
Yes, the patient and her family will benefit from the genetic testing. Genetic testing may
provide you and your family with additional health information and help you make medical
decisions. This could identify the altered genetic makeup in the individual and could help in the the
coping of the cancer risks. Genetic test results may affect cancer treatment decisions such as choice
of surgery—prophylactic mastectomy or oophorectomy in susceptible individuals—or
chemotherapy. It can help women understand their risk for additional cancers to guide medical
decisions about risk management. Also, it can help relatives understand their risk for cancer and take
actions to stay healthy. Test results may affect eligibility for certain clinical trials and research
studies.
7. What are the different cancer prevention or screening strategies for the general population and
those at high risk?
Non-invasive cancer screening tests can lead to an early diagnosis of the specific cancers to
allow the physicians and the patient a more conservative surgical therapy with less morbidity. Key
factors which may influence screening guidelines are the prevalence of the cancer is in the
population, the risks associated with the screening process, and the effect of early cancer diagnosis
with the outcome of the disease. The first figure below shows the screening strategies based from
the American Cancer Society. The second figure shows examples of currently recommended and
possible future precision cancer prevention strategies for selected cancers in the United States.

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8. Explain why surgery is the most effective treatment that offers cure in solid organ tumors.
Surgery plays a vital role in the cancer treatment plan, especially in patients with solid
tumors. Surgery is often used to attempt to cure patients whose tumors are localized at the time of
the diagnosis. After definite cancer diagnosis, curative surgical operations are conducted to remove
or destroy cancerous tissue. Unlike diagnostic surgeries which may remove a small amount of tissue
to confirm the existence and the stage of the disease, curative surgeries take a much more radical
surgical approach, typically resulting in partial or total removal of the organ of origin.
In a curative procedure, a certain amount of normal tissue as well as cancerous tissue may be
removed to obtain adequate margins. The purpose is to minimize the risk of any cancer cells being
left behind, which may result in a recurrence of the cancer. For the same purpose, the surgeon may
also remove the lymph nodes that are adjacent to the tumor.
Resection of isolated metastases (removal of solitary metastases) may be performed in some
cases, especially if there has been a disease-free interval of more than one year after the surgery.
Second-look operations are sometimes performed following adjuvant therapies, but they have little
effect on the final outcome in the great majority of cancer patients.
Depending on your type of cancer and how advanced it is, surgery can be used to remove the
entire tumor—surgery removes cancer that is contained in one area. It also debulk a tumor—
surgery removes some, but not all, of a cancer tumor. Debulking is used when removing an entire
tumor might damage an organ or the body. Removing part of a tumor can help other treatments work
better. Lastly, it eases cancer symptoms—surgery is used to remove tumors that are causing pain
or pressure.

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References:
Curative Surgery. (n.d.). Retrieved from
https://training.seer.cancer.gov/treatment/surgery/types/curative.html
Loomans-Kropp, H. A., & Umar, A. (2019, January 28). Cancer prevention and screening: the next step
in the era of precision medicine. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349901/
Phyllodes Tumors of the Breast: Symptoms and Diagnosis. (2020, January 22). Retrieved from
https://www.breastcancer.org/symptoms/types/phyllodes/diagnosis
Rahner, N., & Steinke, V. (2008, October). Hereditary cancer syndromes. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696972/
Schneider, K. (2019, November 21). Li-Fraumeni Syndrome. Retrieved from
https://www.ncbi.nlm.nih.gov/books/NBK1311/
Siddiqui, I. A., Sanna, V., Ahmad, N., & Mukhtar, H. (2018, August 1). Figure 1: Carcinogenesis phases:
initiation, promotion, progression,... Retrieved from
https://www.researchgate.net/figure/Carcinogenesis-phases-initiation-promotion-progression-
and-metastasis-A-Initiation_fig2_279304092
Ozaki, T., & Nakagawara, A. (2011, March 3). Role of p53 in Cell Death and Human Cancers. Retrieved
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756401/#b10-cancers-03-00994

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