1440
Letters to the Editor
and rare mitotic activity. These features consent the differential diagnosis by squamous cell carcinoma.3,4 In literature, there are few cases of PEH to tattoos, but it is very important that clinicians be aware of this possibility and of the possible development of cutaneous cancer in the site of tattoo. A. Tammaro,1,* A. Narcisi,1 G. Cortesi,1 C. Abruzzese,1 F. Socciarelli,2 F. Pulcini,2 G. De Marco,1 S. Persechino1 1
UOC Dermatology, NESMOS Department, University of Rome Sapienza, Rome, Italy, 2UOC Histopathology, University of Rome Sapienza, Rome, Italy *Correspondence: A. Tammaro. E-mail: [email protected] All authors contributed equally to this report.
References 1 Tammaro A, Tuchinda P, Persechino S, Gaspari A. Contact allergic dermatitis to gold in a tattoo: a case report. Int J Immunopathol Pharmacol 2011; 24: 1111–1113. 2 Jacob CI. Tattoo-associated dermatoses: a case report and review of the literature. Dermatol Surg 2002; 28: 962–965. 3 Cui W, McGregor DH, Stark SP, Ulusarac O, Mathur SC. Pseudoepitheliomatous hyperplasia-an unusual reaction following tattoo: report of a case and review of the literature. Int J Dermatol 2007; 46: 743–745. 4 Goldenberg G, Patel S, Patel MJ, Williford P, Sangueza O. Eruptive squamous cell carcinomas, keratoacanthoma type, arising in a multicolor tattoo. J Cutan Pathol 2003; 35: 62–64. DOI: 10.1111/jdv.12485
Cutaneous spread of primary neuroendocrine breast carcinoma with apocrine differentiation Editor Neuroendocrine breast carcinoma is a rare variant of breast adenocarcinoma recognized in the WHO Classification of Tumours. It is defined by the presence of positive staining for neuroendocrine markers (Synaptophysin or Chromogranin) in more than 50% of the tumoural cells. Few cases of cutaneous involvement by this type of tumour have been described.1,2 We present the first known case of a patient with neuroendocrine breast carcinoma with apocrine differentiation and cutaneous involvement. An 80-year-old woman came to our hospital complaining of a huge bleeding mass in her right breast. The patient related that the lesion started as a palpable lump inside her breast. It was a painless lesion which had been growing slowly for 12 years. Physical examination showed an enormous, hard to the touch lesion, lateralized towards the upper inner quad-
JEADV 2015, 29, 1439–1454
Figure 1 Enormous lesion with hard in consistency located on the right breast with remarkable ulceration.
rant of her right breast. It measured 17 9 13 9 10 cm and presented with ulceration (Fig. 1). Furthermore, an enlarged lymph node was detected in the homolateral axillary region, measuring 5 9 3 cm. The axial CT scan showed infiltration of the pectoralis major muscle by the tumour. CT scan images also showed the enlarged axillary adenopathy and some paratracheal adenopathies. No other pathological findings were noted. A core biopsy was performed. Histological examination revealed a monomorphic tumour cell population with abundant eosinophilic cytoplasm, round nuclei and conspicuous nucleoli, arranged in nests or, less frequently, following a trabecular pattern. The tumoural nests were separated by scarce myxoid connective tissue or by thin fibrovascular stroma. Few typical mitotic figures were noted. Immunohistochemistry showed diffused positive staining for neuroendocrine markers (Chromogranin A and Synaptophysin), gross cystic disease fluid protein-15 (GCDFP-15), oestrogen receptor, progesterone receptor, E-cadherin and BCL-2 (Fig. 2). Ki-67 proliferation index was close to 10%. The tumour cells were negative for cytokeratins 5/6, 14 and 20. Hercep test was negative as well. Altogether, findings were consistent with neuroendocrine adenocarcinoma of the breast with apocrine differentiation and cutaneous involvement. Our patient was treated with 500 mg Fulvestrant intramuscular injections every 4 weeks and adjuvant radiotherapy. Two months after treatment set-up, the mass had reduced by 50%. Five months later, the mass did not show any growth. Neuroendocrine breast carcinomas represent less than 1% of all primary breast carcinomas (3,4). Clinical presentation, morphological features, radiological images and histological findings, in association with immunohistochemical techniques allow for accurate diagnosis. In that sense, the long evolution of the tumour (about 12 years), and the fact that
© 2014 European Academy of Dermatology and Venereology
Letters to the editor
1441
(a)
(b)
(c)
(d)
Figure 2 Histological features of the breast tumor. (a) Monomorphic tumoral population with abundant eosinophilic cytoplasm, round nuclei and conspicuous nucleoli, arranged mainly in nests. The tumor nests are separated by scanty mucinous connective tissue. (H&E, 9400); Immunohistochemical studies of the tumor cell staining positive for synaptophysin (b), chromogranin A (c), and GCDFP-15 (d). (Each, immunohistochemical stain 9400).
the radiological images did not show masses in other locations than the axillary adenopathy, support our diagnosis of cutaneous invasion by a low-grade primary malignant tumour of the breast. The WHO’s most recent classification describes three neuroendocrine breast carcinoma subtypes: solid variant, small cell variant and large cell variant.4 Our patient’s case, however, shows unusual morphological characteristics: monomorphic cells with large eosinophilic granular cytoplasm resembling an A-type apocrine carcinoma, in contrast with the basaloid differentiation previously reported in two similar cases.1,2 We ruled out the diagnosis of apocrine carcinoma on the basis of the morphological features and the positive expression for BCL2, oestrogen and progesterone receptors.4 Our case shows apocrine markers and neuroendocrine markers coexpression. The presence of cells with synchronic apocrine and neuroendocrine differentiation supports the hypothesis of the tumour having originated in a single stem cell with multidirectional differentiation. In that respect, apocrine differentiation has been reported to improve the patients’ long-term survival.5 In conclusion, we highlight the first described case of skin involvement by primary neuroendocrine breast carcinoma with apocrine differentiation, showing a good clinical course with an evolution of more than 12 years.
JEADV 2015, 29, 1439–1454
ndez-Vega,1 P. Coto-Segura,2 J. Santos-Juanes,1,* I. Ferna B. Vivanco-Allende,1 C. Garcıa-Pravia1 1
Department of Pathology, Hospital Univesitario Central de Asturias, Oviedo, Spain, 2Department of Dermatology, Hospital Univesitario Central de Asturias, Oviedo, Spain *Correspondence: J. Santos-Juanes. E-mail: jorgesantosjuanes@gmail. com
References 1 Vidulich KA, Donley SE, Duvic M. Multinodular cutaneous spread in neuroendocrine tumor of the breast: an unusual presentation. Am J Clin Dermatol 2007; 8: 379–383. 2 Boyd AS, Hayes BB. Metastatic small cell neuroendocrine carcinoma of the breast. J Cutan Pathol 2012; 39: 1042–1046. 3 Upalakalin JN, Collins LC, Tawa N, Parangi S. Carcinoid tumors in the breast. Am J Surg 2006; 191: 799–805. 4 Ellis IO, Schnitt SJ, Sastre-Carau X et al. Tumours of breast, neuroendocrine tumours. In Tavasoli FA, Devilee P, eds. World Health Organization classification of tumours: pathology and genetics of tumours of the breast and female genital organs. WHO classification of Tumors Series. IARC Press, Lyon, France, 2003: 32. 5 Sapino A, Righi L, Cassoni P, Papotti M, Gugliotta P, Bussolati G. Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women. Mod Pathol 2001; 14: 768–776. DOI: 10.1111/jdv.12486
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
and rare mitotic activity. These features consent the differential diagnosis by squamous cell carcinoma.3,4 In literature, there are few cases of PEH to tattoos, but it is very important that clinicians be aware of this possibility and of the possible development of cutaneous cancer in the site of tattoo. A. Tammaro,1,* A. Narcisi,1 G. Cortesi,1 C. Abruzzese,1 F. Socciarelli,2 F. Pulcini,2 G. De Marco,1 S. Persechino1 1
UOC Dermatology, NESMOS Department, University of Rome Sapienza, Rome, Italy, 2UOC Histopathology, University of Rome Sapienza, Rome, Italy *Correspondence: A. Tammaro. E-mail: [email protected] All authors contributed equally to this report.
References 1 Tammaro A, Tuchinda P, Persechino S, Gaspari A. Contact allergic dermatitis to gold in a tattoo: a case report. Int J Immunopathol Pharmacol 2011; 24: 1111–1113. 2 Jacob CI. Tattoo-associated dermatoses: a case report and review of the literature. Dermatol Surg 2002; 28: 962–965. 3 Cui W, McGregor DH, Stark SP, Ulusarac O, Mathur SC. Pseudoepitheliomatous hyperplasia-an unusual reaction following tattoo: report of a case and review of the literature. Int J Dermatol 2007; 46: 743–745. 4 Goldenberg G, Patel S, Patel MJ, Williford P, Sangueza O. Eruptive squamous cell carcinomas, keratoacanthoma type, arising in a multicolor tattoo. J Cutan Pathol 2003; 35: 62–64. DOI: 10.1111/jdv.12485
Cutaneous spread of primary neuroendocrine breast carcinoma with apocrine differentiation Editor Neuroendocrine breast carcinoma is a rare variant of breast adenocarcinoma recognized in the WHO Classification of Tumours. It is defined by the presence of positive staining for neuroendocrine markers (Synaptophysin or Chromogranin) in more than 50% of the tumoural cells. Few cases of cutaneous involvement by this type of tumour have been described.1,2 We present the first known case of a patient with neuroendocrine breast carcinoma with apocrine differentiation and cutaneous involvement. An 80-year-old woman came to our hospital complaining of a huge bleeding mass in her right breast. The patient related that the lesion started as a palpable lump inside her breast. It was a painless lesion which had been growing slowly for 12 years. Physical examination showed an enormous, hard to the touch lesion, lateralized towards the upper inner quad-
JEADV 2015, 29, 1439–1454
Figure 1 Enormous lesion with hard in consistency located on the right breast with remarkable ulceration.
rant of her right breast. It measured 17 9 13 9 10 cm and presented with ulceration (Fig. 1). Furthermore, an enlarged lymph node was detected in the homolateral axillary region, measuring 5 9 3 cm. The axial CT scan showed infiltration of the pectoralis major muscle by the tumour. CT scan images also showed the enlarged axillary adenopathy and some paratracheal adenopathies. No other pathological findings were noted. A core biopsy was performed. Histological examination revealed a monomorphic tumour cell population with abundant eosinophilic cytoplasm, round nuclei and conspicuous nucleoli, arranged in nests or, less frequently, following a trabecular pattern. The tumoural nests were separated by scarce myxoid connective tissue or by thin fibrovascular stroma. Few typical mitotic figures were noted. Immunohistochemistry showed diffused positive staining for neuroendocrine markers (Chromogranin A and Synaptophysin), gross cystic disease fluid protein-15 (GCDFP-15), oestrogen receptor, progesterone receptor, E-cadherin and BCL-2 (Fig. 2). Ki-67 proliferation index was close to 10%. The tumour cells were negative for cytokeratins 5/6, 14 and 20. Hercep test was negative as well. Altogether, findings were consistent with neuroendocrine adenocarcinoma of the breast with apocrine differentiation and cutaneous involvement. Our patient was treated with 500 mg Fulvestrant intramuscular injections every 4 weeks and adjuvant radiotherapy. Two months after treatment set-up, the mass had reduced by 50%. Five months later, the mass did not show any growth. Neuroendocrine breast carcinomas represent less than 1% of all primary breast carcinomas (3,4). Clinical presentation, morphological features, radiological images and histological findings, in association with immunohistochemical techniques allow for accurate diagnosis. In that sense, the long evolution of the tumour (about 12 years), and the fact that
© 2014 European Academy of Dermatology and Venereology
Letters to the editor
1441
(a)
(b)
(c)
(d)
Figure 2 Histological features of the breast tumor. (a) Monomorphic tumoral population with abundant eosinophilic cytoplasm, round nuclei and conspicuous nucleoli, arranged mainly in nests. The tumor nests are separated by scanty mucinous connective tissue. (H&E, 9400); Immunohistochemical studies of the tumor cell staining positive for synaptophysin (b), chromogranin A (c), and GCDFP-15 (d). (Each, immunohistochemical stain 9400).
the radiological images did not show masses in other locations than the axillary adenopathy, support our diagnosis of cutaneous invasion by a low-grade primary malignant tumour of the breast. The WHO’s most recent classification describes three neuroendocrine breast carcinoma subtypes: solid variant, small cell variant and large cell variant.4 Our patient’s case, however, shows unusual morphological characteristics: monomorphic cells with large eosinophilic granular cytoplasm resembling an A-type apocrine carcinoma, in contrast with the basaloid differentiation previously reported in two similar cases.1,2 We ruled out the diagnosis of apocrine carcinoma on the basis of the morphological features and the positive expression for BCL2, oestrogen and progesterone receptors.4 Our case shows apocrine markers and neuroendocrine markers coexpression. The presence of cells with synchronic apocrine and neuroendocrine differentiation supports the hypothesis of the tumour having originated in a single stem cell with multidirectional differentiation. In that respect, apocrine differentiation has been reported to improve the patients’ long-term survival.5 In conclusion, we highlight the first described case of skin involvement by primary neuroendocrine breast carcinoma with apocrine differentiation, showing a good clinical course with an evolution of more than 12 years.
JEADV 2015, 29, 1439–1454
ndez-Vega,1 P. Coto-Segura,2 J. Santos-Juanes,1,* I. Ferna B. Vivanco-Allende,1 C. Garcıa-Pravia1 1
Department of Pathology, Hospital Univesitario Central de Asturias, Oviedo, Spain, 2Department of Dermatology, Hospital Univesitario Central de Asturias, Oviedo, Spain *Correspondence: J. Santos-Juanes. E-mail: jorgesantosjuanes@gmail. com
References 1 Vidulich KA, Donley SE, Duvic M. Multinodular cutaneous spread in neuroendocrine tumor of the breast: an unusual presentation. Am J Clin Dermatol 2007; 8: 379–383. 2 Boyd AS, Hayes BB. Metastatic small cell neuroendocrine carcinoma of the breast. J Cutan Pathol 2012; 39: 1042–1046. 3 Upalakalin JN, Collins LC, Tawa N, Parangi S. Carcinoid tumors in the breast. Am J Surg 2006; 191: 799–805. 4 Ellis IO, Schnitt SJ, Sastre-Carau X et al. Tumours of breast, neuroendocrine tumours. In Tavasoli FA, Devilee P, eds. World Health Organization classification of tumours: pathology and genetics of tumours of the breast and female genital organs. WHO classification of Tumors Series. IARC Press, Lyon, France, 2003: 32. 5 Sapino A, Righi L, Cassoni P, Papotti M, Gugliotta P, Bussolati G. Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women. Mod Pathol 2001; 14: 768–776. DOI: 10.1111/jdv.12486
© 2014 European Academy of Dermatology and Venereology
