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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 3  |  Issue : 3  |  Page : 66-69

Dermatofibrosarcoma protuberans, lymphedema, and breast cancer: A rare association


1 Department of Radiation Oncology, CMC, Vellore, Tamil Nadu, India
2 Department of Pathology, CMC, Vellore, Tamil Nadu, India
3 Palliative Care Unit, CMC Hospital, Vellore, Tamil Nadu, India

Date of Web Publication27-Dec-2019

Correspondence Address:
Dr. Kaalindi Singh
Department of Radiation Oncology, CMC Hospital, Vellore, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/oji.oji_26_19

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  Abstract 


A woman with postmastectomy lymphedema presented with a progressive nodular swelling on the affected limb. The biopsy was reported as dermatofibrosarcoma protuberans (DFSP). There is only one other case in literature, where a truncal dermatofibrosarcoma was reported in association with breast cancer. Both tumors had the P53 mutation. In our patient, the breast cancer and the DFSP were both negative for the P53 mutation and it is possible that chronic lymphedema was causative in the formation of the DFSP. More evidence is needed to understand the etiopathogenesis of DFSP occurring in breast cancer patients.

Keywords: Breast cancer, dermatofibrosarcoma protuberans, lymphedema, P53


How to cite this article:
Singh K, Backianathan S, Jennifer A, Susitra D N, George R. Dermatofibrosarcoma protuberans, lymphedema, and breast cancer: A rare association. Oncol J India 2019;3:66-9

How to cite this URL:
Singh K, Backianathan S, Jennifer A, Susitra D N, George R. Dermatofibrosarcoma protuberans, lymphedema, and breast cancer: A rare association. Oncol J India [serial online] 2019 [cited 2020 Feb 25];3:66-9. Available from: http://www.ojionline.org/text.asp?2019/3/3/66/274093




  Introduction Top


Dermatofibrosarcoma protuberans (DFSP) constitutes <2% of spindle cell tumors and <0.1% of all malignancies.[1] It originates in the mesenchymal tissue, is locally aggressive, and may infiltrate adjacent muscle. It often presents as a brownish-purple plaque or nodule on the skin of the trunk. Lesions of the extremities are less common. Breast cancer, on the other hand, constitutes 11.6% of all cancers with an annual tumor burden of 2.08 lakh. Worldwide, it is the most common cancer in women and the second most common malignancy after lung cancer.[2] Breast cancer is associated with a variety of soft tissue sarcomas. However, association of carcinoma breast with DFSP is rarely reported.[3] Here, we present the case of a DFSP lesion of the extremity in a patient with breast cancer and lymphedema.


  Case Report Top


In July 2011, a 61-year-old postmenopausal woman presented with a 3-month history of a lump in the right breast. On examination, there was a 4 cm × 4 cm retroareolar mass associated with nipple retraction and an enlarged ipsilateral axillary node. She was clinically staged as cT2N1M0. Fine-needle aspiration cytology from swelling was reported as invasive carcinoma. Her metastatic workup was negative, and she underwent right modified radical mastectomy with right axillary clearance. Histopathology of the specimen was reported as infiltrating duct carcinoma, Grade I. The tumor was <0.1 cm from the deep resection margin. Lymphovascular invasion was present; perineural invasion was not seen. Fifteen lymph nodes were dissected, all of which were free of tumor. The final stage was pT3pN0cM0. The specimen was negative for estrogen receptor and progesterone receptor (ER and PR). HER2 neu was not done as the patient was not willing for the same.

Postoperatively, the patient received six cycles of cyclophosphamide (600 mg/m2) and doxorubicin (60 mg/m2), followed by radiation therapy to the chest wall with the dose of 54 Gy/27 fractions and to the supraclavicular fossa with the dose of 46 Gy/23 fractions over a period of 5 ½ weeks. Given ER/PR negativity, she was not given any adjuvant hormonal therapy. After completion of treatment in February 2012, the patient was kept on regular follow-up and remained disease free.

On the second follow-up, the patient complained of right upper limb edema which gradually increased despite conservative treatment. Five years posttreatment, a nontender hyperpigmented nodularity was noticed on the right upper arm, about 4 cm × 3 cm in size. The patient stated that the nodularity had been there previously, before the onset of breast lump. There was no history of increase in size of the lesion, and as it did not cause her any symptoms, it was decided to keep the lesion on follow-up. In April 2018, a year after the arm nodule was first documented, the patient complained of an increase in size of the lesion, associated with mild pain [Figure 1].
Figure 1: Brownish-purple nodular lesion of size approximately 5 cm × 5 cm over the left upper arm of the patient

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Thus, a biopsy was done which was reported as pigmented DFSP [Figure 2]. Immunohistochemistry was negative for CD117, ER and PR, and P53 [Figure 3].
Figure 2: Storiform arrangement of spindle cells (H and E, ×100) suggestive of dermatofibrosarcoma protuberans

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Figure 3: Dermatofibrosarcoma protuberans negative for P53

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P53 mutation was also tested on the primary breast malignancy to establish any genetic correlation between the two malignancies, as was previously documented in one case report.[3] However, it was reported as negative [Figure 4].
Figure 4: Infiltrating duct carcinoma of the breast, negative for P53

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A chest X-ray was done as part of metastatic workup, which showed a lung lesion in the left lower lobe suspicious of metastasis. As the patient was unwilling for any further investigations, histopathological examination specimen was not taken from the lesion to determine whether its origin was from breast cancer or DFSP.

In view of preexisting excessive lymphedema, surgery and radiotherapy was not considered an option for the DFSP lesion. The patient was also not a candidate for imatinib treatment in view of CD117 negativity. Thus, it was decided to offer the patient best supportive care.

Five months after the diagnosis of DFSP, the lesion has increased from 4 cm × 4 cm size to 6 cm × 4 cm without ulceration or bleeding. The margins have become more irregular and nodular. The patient is being managed conservatively for her symptoms.


  Discussion Top


Several factors have been implicated in the genesis of DFSP. These include previous trauma, surgical scars, burns, chronic lymphedema, chronic irritation, immunization, and exposure to toxic agents.[4] Some genetic aberrations, including P53, have also been shown to be associated with DFSP. P53 is most frequently expressed in the fibrosarcomatous variant of DFSP which tends to be more aggressive. Immunohistochemically, DFSP stains positive for CD34 in approximately 80% of patients and stains negatively for XIIIa.[5]

Clinically, DFSP has a long natural history and remains unnoticed for prolonged periods until it grows in size or becomes painful. The tumor invades the underlying dermis and subcutis with tentacle-like projections which can lead to local recurrences after surgery.[6] Overall, DFSP has a greater tendency for local recurrence rather than distant metastasis. However, the fibrosarcomatous variant of DFSP is known for its aggressive behavior and higher local recurrence as well as distant metastasis. In a retrospective study by Hayakawa et al., the distant metastasis rate in ordinary DFSP was 1.7% and in fibrosarcomatous variant was 57%, with lung being the most common site of metastasis.[7] Different series have reported different rates of metastasis, but it is generally understood that metastasis in fibrosarcomatous variant is much higher (10%–15%) than in ordinary DFSP (<5%).[6]

Complete surgical excision with negative margins is the cornerstone of treatment for DFSP. Surgery should aim to excise the tumor with margins of 2–4 cm up to the fascia. Mohs Micrographic Surgery (MMS), where the tumor is removed layer by layer, has been shown to be superior to excision with uniform margins. MMS is associated with fewer local recurrences as pseudopod-like projections of the tumor can be microscopically detected and excised.[8]

Radiotherapy has a role in large inoperable tumors or in tumors with positive margins where re-excision is not possible. It can also be used in ulcerating and bleeding tumors for palliation. Systemic therapy with imatinib has shown significant response rates. It targets the platelet-derived growth factor receptors pathway, which is overexpressed in DFSP.[4]

There is only one published case report documenting the association of DFSP with breast cancer previously and P53 mutation was overexpressed in both the malignancies.[3] In our patient, we studied P53 mutation in both the malignancies in view of academic interest without any major therapeutic implications. We found both the malignancies to be negative for the P53 mutation. P53 negativity in both the malignancies, however, still does not rule out genetic association, although P53 mutation as a causative factor can be ruled out in this patient.

We could also postulate that chronic lymphedema may have played a role in the aberrant growth of a preexisting benign lesion in this patient. It is well-understood that lymphatic vasculature coordinates local inflammation and immunity, and it has been suggested that chronic lymphedema may be associated with local immunodeficiency permitting oncogenesis,[9],[10],[11] thus emphasizing the need for minimizing late complications of surgery and radiotherapy in patients with breast cancer, by optimizing extent of surgery and radiotherapy along with institution of preventive measures such as physiotherapy immediately after surgery.


  Conclusion Top


Lymphedema is common in patients after treatment of breast cancer. The affected limb should be carefully examined to look for nodal recurrences, cutaneous secondaries, or second primaries. Because this lesion was present in the patient before the onset of breast cancer, a thorough clinical examination and high clinical index of suspicion for the skin lesion could have led to an earlier diagnosis and a probability of cure. We could not establish any genetic correlation between breast cancer and DFSP. However, if any such association exists, its therapeutic implications would still remain to be understood.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol 2007;56:968-73.  Back to cited text no. 1
    
2.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.  Back to cited text no. 2
    
3.
Beech DJ, Long AB, Long WP. Dermatofibrosarcoma protuberans and breast cancer: Genetic link or coincidental association? Am Surg 2004;70:543-5.  Back to cited text no. 3
    
4.
Bichakjian CK, Olencki T, Alam M, Andersen JS, Berg D, Bowen GM, et al. Dermatofibrosarcoma protuberans, version 1.2014. J Natl Compr Canc Netw 2014;12:863-8.  Back to cited text no. 4
    
5.
Hisaoka M, Okamoto S, Morimitsu Y, Tsuji S, Hashimoto H. Dermatofibrosarcoma protuberans with fibrosarcomatous areas. Molecular abnormalities of the p53 pathway in fibrosarcomatous transformation of dermatofibrosarcoma protuberans. Virchows Arch 1998;433:323-9.  Back to cited text no. 5
    
6.
Zeitouni N, Cavanaugh K, DuPont J. Dermatofibrosarcoma protuberans: An update and review. Curr Derm Rep 2015;4:195-204.  Back to cited text no. 6
    
7.
Hayakawa K, Matsumoto S, Ae K, Tanizawa T, Gokita T, Funauchi Y, et al. Risk factors for distant metastasis of dermatofibrosarcoma protuberans. J Orthop Traumatol 2016;17:261-6.  Back to cited text no. 7
    
8.
Foroozan M, Sei JF, Amini M, Beauchet A, Saiag P. Efficacy of Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans: Systematic review. Arch Dermatol 2012;148:1055-63.  Back to cited text no. 8
    
9.
Zaleska M, Olszewski WL, Durlik M, Miller NE. Signaling proteins are represented in tissue fluid/lymph from soft tissues of normal human legs at concentrations different from serum. Lymphat Res Biol 2013;11:203-10.  Back to cited text no. 9
    
10.
Szuba A, Rockson SG. Lymphedema: Anatomy, physiology and pathogenesis. Vasc Med 1997;2:321-6.  Back to cited text no. 10
    
11.
Berebichez-Fridman R, Deutsch YE, Joyal TM, Olvera PM, Benedetto PW, Rosenberg AE, et al. Stewart-treves syndrome: A case report and review of the literature. Case Rep Oncol 2016;9:205-11.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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