Case Reports in Dermatological Medicine

Case Reports in Dermatological Medicine / 2018 / Article

Case Report | Open Access

Volume 2018 |Article ID 2812439 | https://doi.org/10.1155/2018/2812439

Jacqueline Deen, Nick Mellick, Laura Wheller, "Concurrent Diagnoses of Cutaneous Sarcoidosis and Recurrent Metastatic Breast Cancer: More than a Coincidental Occurrence?", Case Reports in Dermatological Medicine, vol. 2018, Article ID 2812439, 6 pages, 2018. https://doi.org/10.1155/2018/2812439

Concurrent Diagnoses of Cutaneous Sarcoidosis and Recurrent Metastatic Breast Cancer: More than a Coincidental Occurrence?

Academic Editor: Jaime A. Tschen
Received17 Jul 2018
Revised20 Aug 2018
Accepted27 Aug 2018
Published05 Sep 2018

Abstract

Sarcoidosis is a rare, chronic, multisystem disease of unknown aetiology, characterised by non-caseating epithelioid cell granulomas. Its association with internal malignancy, in particular haematological cancers has been strongly documented in the literature, while its link with solid organ malignancies is less extensively reported. We present an atypical case of cutaneous sarcoidosis occurring in association with breast cancer recurrence in a 49-year-old female. Physician recognition of this link between sarcoidosis and internal malignancy is vital because many cases of sarcoidosis in association with neoplasia present initially, or even exclusively, with cutaneous sarcoidal lesions that may precede the development of cancer by several years, or as in our case, present as a cutaneous marker of concomitant underlying malignancy. Our case highlights the importance of age-appropriate cancer screening in additional to a routine work-up for systemic sarcoidosis in a patient with cutaneous sarcoidosis.

1. Introduction

Sarcoidosis is a chronic, idiopathic, multisystem disease, characterised by non-caseating epithelioid cell granulomas. The lungs are involved in more than 90% of cases, but the lymphatic system, eyes, and skin may also be affected. Less common but usually more severe forms can involve the liver, spleen, central nervous system, heart, upper respiratory tract, and bones. Its pathogenesis appears to correspond to an aberrant immune response in a susceptible host. Sarcoidosis typically affects young adults, with a slight female general predominance [1, 2].

Various diseases have been associated with sarcoidosis, including autoimmune disorders such as rheumatoid arthritis, psoriasis, vasculitis, thyroid disease, systemic sclerosis, and Sjogren syndrome. Haematological malignancies, in particular lymphoproliferative disorders such as Hodgkin lymphoma, are most strongly associated with sarcoidosis compared to solid organ malignancies [2, 3]. We present a rare case of cutaneous sarcoidosis occurring in association with breast carcinoma.

2. Case Report

A 49-year-old female presented with a 2-month history of asymptomatic lesions on the left knee found incidentally on routine full skin examination. The patient was otherwise well, with no pulmonary or systemic symptoms.

She had a past history of breast cancer diagnosed 4 years ago, managed by lumpectomy and adjuvant chemoradiotherapy achieving remission. The patient had regular cancer surveillance and was currently on adjuvant tamoxifen, with a planned duration of 10 years. Her other notable medical history included lifelong asthma, gastrooesophageal reflux disease, depression, subacute thyroiditis and previous shoulder, and knee arthroscopies. Her regular medications included tamoxifen, pantoprazole, venlafaxine, budesonide/formoterol, and terbutaline. She was a lifetime non-smoker and rarely consumed alcohol. The patient had no family history of autoimmune conditions.

Examination revealed numerous erythematous-to-brown, non-tender papules occurring on the anterior left knee (Figure 1). On the right foot, at the site of a scar from prior cryotherapy for plantar warts, the patient had a similar area of firm indurated erythematous-to-brown change. Dermoscopy of both sites showed orange and yellow translucent globules (“apple-jelly” sign). There were no skin lesions detected on full skin examination suspicious for malignancy. There was no lymphadenopathy and systemic examination was otherwise unremarkable.

Skin biopsy showed multiple, variably sized naked sarcoidosis type granulomas scattered throughout the dermis (Figure 2). Chest radiograph showed bilateral hilar lymphadenopathy and serum angiotensin-converting enzyme was elevated at 107 U/L. Other laboratory tests were within normal limits (full blood count, liver and renal function tests, and calcium and inflammatory markers). Further investigations excluded systemic sarcoidosis (cardiac MRI and CT-PET scan). The CT PET ordered during systemic work-up, however, showed a solitary lesion in the T10 vertebra and subsequent biopsy proved recurrent metastatic breast cancer.

The patient’s management was then deferred to a medical oncologist for ongoing care of her metastatic breast cancer. She received stereotactic radiation to her spinal lesion and was commenced on a special access program with ribociclib. Following breast cancer treatment, cutaneous sarcoidal lesions completely resolved.

3. Discussion

Cutaneous involvement presents in 25% of patients with systemic sarcoidosis and may be the only manifestation [4]. Dermatologists are frequently the first clinicians to identify sarcoidosis as specific skin lesions are often the presenting sign and skin biopsy enables early diagnosis. Skin lesions are extremely variable and may be specific or nonspecific. Specific lesions are those that histologically display noncaseating granulomas, which manifest clinically as maculopapules, plaques, lupus pernio, scar-sarcoidosis, and subcutaneous sarcoidosis. Nonspecific lesions lack histological evidence of sarcoid granulomas and the most significant lesions are erythema nodosum. In isolated cutaneous disease, further evaluation is essential as transformation into systemic sarcoidosis occurs in approximately one-third of patients within three years [1, 2].

Various diseases have been associated with sarcoidosis. Previously, an association between sarcoidosis and malignancy has been described, although no clear relationship has been identified. In most cases, sarcoidosis was diagnosed before the detection of an associated neoplasm. Haematological malignancies remain most strongly associated compared to solid tumours [13]. Brincker and Wilbek in 1974 were first to describe this association, reporting that, in patients with sarcoidosis, lymphoma occurred 11 times more frequently and lung cancer occurred three times more frequently compared with the general population [5].

Previous literature cases of sarcoidosis occurring with breast cancer are summarised in Table 1. The average patient age was 53 years, with 98.3% being female. In 30 (48.4%) patients the identification of sarcoidosis preceded the diagnosis of breast cancer; in 18 (29.0%) patients breast cancer diagnosis preceded sarcoidosis; and in 14 (22.6%) patients both diseases occurred concomitantly. The average time interval between the diagnosis of sarcoidosis and breast cancer was 8.3 years (range 1-34 years). When breast cancer predated sarcoidosis, the average interval was 4.1 years (range 0.6-12 years). In our case, the patient age at diagnosis was 49 years, which is similar to what was described in the literature.


ReferenceSexPatient age (years)Interval b/t diseases (years)Sarcoidosis onsetTumour type

Prior et al. (1952) [6]F595PBreast adenocarcinoma

Brincker et al. (1974) [5]FNSNSPNS
FP
FP
MP

Suen JS et al (1990) [7]F500.7ABreast cancer (stage II)

Shah AK et al (1990) [8]F363PInvasive ductal carcinoma

Von Knorring et al. (1976) [9]F745PNon-metastasizing breast carcinoma

Whittington R et al. (1986) [10]F520.6AInfiltrating ductal carcinoma
F425PMetastatic breast cancer

Reich J et al. (1995) [11]F4710AIntraductal breast carcinoma
F559PInfiltrating ductal breast carcinoma

Brechtek B et al. (1996) [4]F581PNS

Seersholm N et al. (1997) [12]NSNSNSPNS

Romer FK et al. (1998) [13]FBetween 19-78 yearsNSPNS
FP
FP
FP
FP
FP

Askling J et al. (1999) [14]NSNSNSPNS
NSPNS

Lower EE et al. (2001) [15]F255PInvasive ductal carcinoma
F575PInfiltrating ductal carcinoma
F588PInvasive ductal carcinoma
F402AInvasive ductal carcinoma
F491AInvasive ductal carcinoma
F382AInvasive ductal carcinoma
F361AInvasive ductal carcinoma
F578AInvasive ductal carcinoma
F550CInvasive ductal carcinoma
F430CIntraductal carcinoma

Garcia et al. (2003) [16]F443PInvasive lobular breast carcinoma with ductal and mucinous features

Chen W et al. (2004) [17]FNSNSPNS
FNS0CNS

Van der Hoeven JJ et al. (2004) [18]FNS0CDuctal carcinoma of breast

Gusakova I et al. (2007) [19]F696AInfiltrating ductal carcinoma of breast
F604AInfiltrating ductal carcinoma of breast

Tolaney SM et al. (2007) [20]F470CInvasive lobular carcinoma of breast
F512AInvasive ductal carcinoma
F310CInvasive ductal carcinoma

Ataergin S et al. (2009) [21]F7512ABreast cancer (T3N1M0)

Viswanath L et al. (2009) [22]F502AInfiltrating ductal carcinoma breast

Ito T et al. (2010) [23]F906AMetastatic breast cancer
F524AInvasive ductal carcinoma breast

Alexandrescu DT et al. (2011) [1]F728PNS
F464PNS
F465PInfiltrating ductal carcinoma of breast

Bush E et al. (2011) [24]F420CInfiltrating ductal carcinoma of breast

Nishioka M et al (2012) [25]F790CRecurrent breast cancer (local)

DeFilippis EM et al (2013) [26]F630CStage 1 breast cancer

Akhtari et al. (2014) [27]F470CDuctal invasive carcinoma

Kim et al. (2014) [28]F442ADuctal invasive carcinoma

Zivin et al. (2014) [29]F320CDuctal invasive carcinoma

Altinkaya et al. (2015) [30]F700CDuctal invasive carcinoma

Conte et al. (2015) [31]F500CDuctal invasive carcinoma

El Hammoumi (2015) [32]F513ALobular carcinoma breast

Chen J et al. (2015) [33]F627AInfiltrating ductal carcinoma
F540CInfiltrating ductal carcinoma
F5024PInfiltrating ductal carcinoma
F6334PInfiltrating ductal carcinoma
F779PInfiltrating ductal carcinoma

Present caseF490CRecurrent metastatic breast cancer

F: female, patient age: age at concurrent disease diagnosis, interval b/t diseases: interval between both diseases (sarcoidosis and breast cancer).
P: preceded breast cancer diagnosis; C: occurred concomitantly with breast cancer diagnosis; A: occurred after breast cancer diagnosis.

Our case is unique in that the cutaneous sarcoidosis most likely occurred around the same time the patient’s breast cancer recurrence was diagnosed and investigation for systemic sarcoidosis revealed her metastatic disease. This may be an incidental finding or indicate that dysregulation of the immune system mediated by either the breast cancer or sarcoidosis lead to the granulomatous inflammation of sarcoidosis or neoplasm, respectively [3, 4, 34]. In addition, there was complete resolution of the cutaneous sarcoidal lesions following treatment of the patient’s metastatic breast cancer, strengthening the correlation between both entities.

Recognition by physicians of this link between sarcoidosis and internal malignancy is vital because many cases of sarcoidosis in association with neoplasia present initially, or even exclusively, with cutaneous sarcoidal lesions that may precede the development of cancer by several years or as in our case, present as a cutaneous marker of concomitant underlying malignancy. Thus, in addition to routine screening for systemic sarcoidosis, patients diagnosed with cutaneous sarcoidosis should be closely followed up, particularly including age-appropriate cancer screening to exclude the development of associated malignancy [1].

Conflicts of Interest

The authors declare that there are no conflicts of interest.

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Copyright © 2018 Jacqueline Deen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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