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Advances in Anatomic Pathology:
doi: 10.1097/PAP.0b013e31820ce11f
Letters to the Editor

Spontaneous Complete Regression in Merkel Cell Carcinoma After Biopsy

Val-Bernal, José Fernando MD, PhD*; García-Castaño, Almudena MD; García-Barredo, Rosario MD; Landeras, Rosa MD; De Juan, Ana MD; Garijo, María Francisca MD, PhD*

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Departments of *Anatomical Pathology


Service of Oncology, Marqués de Valdecilla University Hospital, Medical Faculty, University of Cantabria Santander, Spain

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To the Editor:

We read with interest the authoritative study by Calder and Smoller1 on new insights into Merkel cell carcinoma (MCC) which was published in the May issue of the journal. In this study, the authors review the nomenclature, cell origin, clinical presentation, pathogenesis, histopathology, predictors of prognosis, sentinel lymph node biopsy, and treatment of this tumor. However, a topic that the authors do not mention is the complete spontaneous regression (CSR) that can be observed in MCC.

Despite its high grade of malignancy cases of CSR in MCC has been reported. CSR in this tumor is an uncommon and poorly understood phenomenon. A review of the literature documents 28 published cases of CSR.2–10

Herein, we present a new case of CSR that occurred after a tru-cut biopsy.

An 86-year-old woman presented in March 2010 with a rapidly growing tumor on her right forearm which had appeared 3 months earlier. Physical examination showed a solitary, firm, nontender, nonulcerated, dome shaped, red nodule more than 3 cm in its greatest diameter. The regional lymph nodes were not enlarged. Routine hematology tests and biochemical values were normal.

Contrast-enhanced T1-weighted fat-saturated magnetic resonance image scan through the distal arm showed a tumor with sharply defined margins, measuring 3.5×1.5×2 cm, within the subcutaneous fat, and intense mostly inhomogeneous contrast enhancement. Enhancement of the epidermis was also noted (Fig. 1).

Figure 1
Figure 1
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A tru-cut biopsy with echographic control was performed. Pathologic examination of the specimen showed a neoplasm consisted of small, round cells of uniform size in diffuse pattern of growth (Fig. 2A). The cells showed hyperchromatic nuclei and scanty of amphophilic cytoplasm with borders vaguely defined. There were numerous mitotic figures and scattered apoptotic fragments. In one area the cells were spindled shaped. A moderate lymphocytic infiltrate was present in the background. Tumor cells showed strong reactivity for cytokeratin AE1/3 (Fig. 2B), cytokeratin 20, epithelial membrane antigen, synaptophysin, neurofilaments, and neuron-specific enolase. The cytokeratins and neurofilaments showed a perinuclear punctuate (dot-like pattern) expression. Negativity for cytokeratin 7 and Ber-Ep4 was observed. The lymphocytic infiltrate was an admixed of CD3 (Fig. 2C) and CD20+ cells, with T-cell predominance. A diagnostic of MCC was made on the base of these findings.

Figure 2
Figure 2
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Thoracoabdominal computed tomography showed no sign of malignancy of internal organs or metastases in lymph nodes.

The patient was referred for surgical excision of the lesion. In a few weeks after biopsy the subcutaneous neoplasm had drastically decreased in size. However, to remove the residual process completely, a surgical resection of the area was performed on June 2010, 10 weeks after the initial biopsy. Histopathologic examination of the specimen showed subcutaneous fibrosis, dense nodular lymphocytic infiltrate, giant cell granulomas, and scattered hemosiderophages. The infiltrate showed a predominance of CD3+ cells. No tumor cells were found (Fig. 2D).

MCC is an uncommon, highly aggressive neuroendocrine carcinoma of the skin that has a predilection for the upper body, predominantly affecting elderly whites and immunosuppressed individuals. The lesion is more common in women. The calculated annual incidence of MCC in whites is 0.22 per 100,000.11 The incidence has been increasing in the last 20 years. The lesion is associated with a poor prognosis as it has a high rate of local recurrence, regional lymph node metastasis, and distant metastases.

Despite its highly malignant nature, cases of CSR have occasionally been reported. CSR is defined as disappearance of the neoplasm and substitution for a mononuclear inflammatory cell infiltrate without any treatment. Occasionally, the tumor is replaced by foam cells.12 The estimated rate of regression in MCC is 1.4%.13 The cases with CSR occurred in patients before planned treatment could be initiated, in patients that refused treatment, or in patients considered too ill from other processes to be considered candidates for treatment. As treatment for MCC is usually initiated quickly after diagnosis, we do not know the real incidence of CSR in this disorder.13

CSR in MCC is more common in women; when the primary site is the head or neck; and after biopsy or fine needle aspiration cytology. CSR can occur either in localized and in widely disseminated cases. In contrast, recurrence after CSR has not been reported.

The molecular mechanism to induce CSR is unclear. It is thought to involve T-cell-mediated response and apoptosis. MCC was recently found to be associated with a polyomavirus called Merkel cell polyomavirus. Feng et al14 showed the integration of polyoma DNA within MCC genome in a clonal pattern, suggesting that viral infection and integration preceded clonal expansion of the tumor cells. The recognizing of the Merkel cell polyomavirus antigen by immune cells might induce apoptosis of MCC cells and CSR.6 The fact that most cases have undergone biopsy before CSR suggests the activation of an immune response stimulated by the surgical procedure. In contrast, other virus associated tumors can show complete CSR.15–17 Immunomodulation to the viral infection that could be induced by the traumatic effects of the biopsy can be hypothesized.

In conclusion, CSR is a significant event in MCC. A diagnostic procedure such as biopsy or fine needle aspiration cytology can be a trigger of regression. This fact suggests that MCC can be responsive to immunological reactions. Further research in the mechanism of CSR in MCC could contribute to improve the treatment and offer a better expectation of prognosis.

José Val-Bernal MD, PhD

Departments of *Anatomical Pathology

Almudena García-Castaño MD

†Service of Oncology, Marqués de Valdecilla University Hospital, Medical Faculty, University of Cantabria Santander, Spain

Rosario García-Barredo MD


Rosa Landeras MD


Ana De Juan MD

†Service of Oncology, Marqués de Valdecilla University Hospital, Medical Faculty, University of Cantabria Santander, Spain

María Garijo MD, PhD

Departments of *Anatomical Pathology

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1. Calder KB, Smoller BR. New insights into Merkel cell carcinoma Adv Anat Pathol.. 2010;17:155–161

2. Torroni A, Loré B, Iannetti G. The importance of the head and neck region in regression of advanced MCC: a clinical report J Craniofac Surg.. 2007;18:1173–1176

3. Kubo H, Matsushita S, Fukushige T, et al. Spontaneous regression of recurrent and metastatic Merkel cell carcinoma J Dermatol.. 2007;34:773–777

4. Richetta AG, Mancini M, Torroni A, et al. Total spontaneous regression of advanced Merkel cell carcinoma after biopsy: review and a new case Dermatol Surg.. 2008;34:815–822

5. Turk T, Orlic ZC, Smoljan I, et al. Spontaneous regression of Merkel cell carcinoma in a patient with chronic lymphocytic leukaemia: a case report J Med Case Reports.. 2009;3:7270

6. Yagi Y, Fujisawa A, Makiura M, et al. Spontaneous regression of Merkel cell carcinoma after biopsy J Dermatol.. 2009;36:312–313

7. Karkos PD, Sastry A, Hampal S, et al. Spontaneous regression of Merkel cell carcinoma of the nose Head Neck.. 2010;32:411–414

8. Ciudad C, Avilés JA, Alfageme F, et al. Spontaneous regression in Merkel cell carcinoma: report of two cases with a description of dermoscopic features and review of the literature Dermatol Surg.. 2010;36:687–693

9. Hassan SJ, Knox M, Griffin M, et al. Spontaneous regression of metastatic Merkel cell carcinoma Ir Med J.. 2010;103:21–22

10. Woolf JC, Trites JR, Walsh NM, et al. Complete spontaneous regression of metastatic Merkel cell carcinoma: a case report and review of the literature Am J Dermatopathol.. 2010 . [E-pub ahead of print].

11. Kaae J, Hansen AV, Biggar RJ, et al. Merkel cell carcinoma: incidence, mortality, and risk of other cancers J Natl Cancer Inst.. 2010;102:793–801

12. Maruo K, Kayashima KI, Ono T. Regressing Merkel cell carcinoma: : a case showing replacement of tumor cells by foamy cells Br J Dermatol.. 2000;142:1184–1189

13. Connelly T. Regarding complete spontaneous regression of Merkel cell carcinoma Dermatol Surg.. 2009;35:721

14. Feng H, Shuda M, Chang Y, et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma Science.. 2008;319:1096–1100

15. Chiu LS, Choi PC, Luk NM, et al. Spontaneous regression of primary cutaneous Epstein-Barr virus-positive, CD30-positive anaplastic large T-cell lymphoma in a heart-transplant recipient Clin Exp Dermatol.. 2009;34:e21–e24

16. Adiguzel C, Bozkurt SU, Kaygusuz I, et al. Human herpes virus8-unrelated primary effusion lymphoma-like lymphoma: : report of a rare case and review of the literature APMIS.. 2009;117:222–229

17. Abe R, Ogawa K, Maruyama Y, et al. Spontaneous regresión of diffuse large B-cell lymphoma harbouring Epstein-Barr virus: a case report and review of the literature J Clin Exp Hematop.. 2007;47:23–26

Cited By:

This article has been cited 1 time(s).

Journal of Investigative Dermatology
Tumor-Specific T Cells in Human Merkel Cell Carcinomas: A Possible Role for Tregs and T-Cell Exhaustion in Reducing T-Cell Responses
Dowlatshahi, M; Huang, V; Gehad, AE; Jiang, Y; Calarese, A; Teague, JE; Dorosario, AA; Cheng, JW; Nghiem, P; Schanbacher, CF; Thakuria, M; Schmults, CD; Wang, LC; Clark, RA
Journal of Investigative Dermatology, 133(7): 1879-1889.
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© 2011 by Lippincott Williams & Wilkins.


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