Letters to the Editor
1250
6 Ishida H, Imai K, Honma K, Tamura S, Imamura T, Ito M et al. GATA2 anomaly and clinical phenotype of a sporadic case of lymphedema, dendritic cell, monocyte, B and NK cell (DCML) deficiency, and myelodysplasia. Eur J Pediatr 2012; 171: 1273–1276. 7 Muszynski MA, Zerbe CS, Holland SM, Kong HH. A woman with warts, leg swelling and deafness. J Am Acad Dermatol 2014; 71: 577–580. DOI: 10.1111/jdv.13183
A case of inflammatory myofibroblastic tumour of the right labium majus Editor Inflammatory myofibroblastic tumour (IMT) is a rare massforming lesion characterized by fibroblastic or myofibroblastic spindle cell proliferations with varying degrees of inflammatory cell infiltration, prevalent lymphocytes, plasma cells and histiocytes.1 The tumour occurs most commonly in the lungs, where
it presents genuinely benign behaviour. Even though rare, extrapulmonary IMTs have been reported mostly in the bladder, mesenteric and mediastinum areas, and is characterized by different, more aggressive behaviour.2 Yet only 18 cases of cutaneous IMT have been reported in the literature.3–7 The clinical presentation of cutaneous IMT is not specific and it varies in size and shape. Patients generally present with a mass but without specific symptoms, so it seldom enters differential diagnosis at the time of the initial evaluation. Recently, we observed a case of cutaneous IMT of the vulva. A 38-year-old woman presented with a small vulvar nodular lesion of the right labium majus. The lesion was reported to have been present for more than 3 years, with asymptomatic growth during this time up to its actual size. On physical examination, the lesion was not visible, whereas it was evidenced by palpation examination. It presented as a round, hard, not pulsating mass of 2 cm diameter, fixed at the near tissues, with the over skin normal for colour and aspect. There were no lymphadenopathies or constitutional symptoms, and the laboratory findings were unremarkable. The preoperative ultrasound examination was not exhaustive, showing a mild vascularized homogeneous and
(a)
(b)
(c)
(d)
Fig. 1 (a) A compact fascicular spindle cells proliferation with variable myxoid and collagenized regions. Presence of lymphoid hyperplasia in the dermis and subcutis, with prevalence of B cells area organized in lymphoid nodules with germinal centre formations. Most of these nodules were neovascularized and with an important infiltrate of immature plasma cells, mainly IgG + (haematoxylin and eosin stain: original magnification, 950). The immunochemistry analysis highlighted the negativity of the lymphoid cells at CD15, CD30 and EMA. The germinal centre formations were colonalized by small T cells CD3+ e BCL2. (b) Furthermore, there was a myofibroblastic proliferation with immunohistochemical cytoplasmic positivity for ALK1 (original magnification, 9100). Using immunohistochemistry, the tumour cells are also positive for p80/ALK1. (c) The spindle cells were negative for S-100 protein (immunohistochemistry for S-100, original magnification, 9200). (d) Staining for smooth muscle actin (SMA) highlighted the spindle cells, confirming their myofibroblastic nature (immunohistochemistry for SMA, original magnification, 9200).
JEADV 2016, 30, 1195–1252
© 2015 European Academy of Dermatology and Venereology
JEADV 2016, 30, 1195–1252
+
Rare
+
+
+
N/A
+
Not contiguous with epithelium; contains pleomorphic histiocytic cells, giant cells with atypical bizarre nuclei. Surrounds without destroying adnexa
Diffusely infiltrative, mildly atypical spindle cells in fascicles within a collagenous/hyalinized/myxoid/stroma. Scattered tumour giant cells, focal lymphocytes and plasma cells mean mitotic rate 2/10HPF, and necrosis
Three patterns: (1) Myxoid, vascular, with inflammatory areas; (2) Compact spindle cells with inflammatory cells; (3) Sparsely cellular with collagen.
Low-grade myofibroblastic sarcoma (myofibrosarcoma)
Extrapulmonary inflammatory myofibroblastic tumour
Atypical fibroxanthoma
+/
+/
Mitotically active; cellular lesion with plump immature fibroblasts in short irregular fascicles with prominent nucleoli
Nodular fasciitis
+/
+
Predominantly myxoid stroma with prominent pleomorphism, stellate or tripolar nuclei may be seen
Myxoid myxofibrosarcoma
Rare
+/
+/
+
Bland spindle cells in whorls and fascicles; fibrous areas alternate with myxoid stroma. Mild pleomorphism with thick collagen bundles
Fibromyxoid sarcoma
+/
Rare
Cytokeratin
N/A
N/A
+/
Rare
+
Epithelial membrane antigen
Immunohistochemical profile Desmin
+
+
Lesion was deeply located within the subcutaneous tissue and consisted of interlacing fascicles of predominant histiocyte-like spindle cells intermingled with pleomorphic giant cells with bizarre large nuclei (bilobed and multilobed) and prominent eosinophilic nucleoli. Prominent hyaline collagen bundles surrounded by tumour cells are usually observed, predominantly at the periphery of the lesion.
Atypical fibrous histiocytoma
+
Diffuse infiltration of the skin and the subcutaneous fatty tissue by densely packed, cytologically relatively uniform, spindle-shaped tumour cells, arranged in a characteristic storiform (mat-like) shape. A typical feature is the spread of tumour cells along the septae of the subcutaneous fatty tissue as well as their diffuse permeation. Fibrosarcomatous DFSP typically appears with an abrupt or gradual transition into cell-rich spindle-cell fascicles with cytological atypia and an increased mitotic figure rate.
Dermatofibrosarcoma protuberans
Nodular or dense diffuse infiltrates involving the entire dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles between the spindled cells were present in one case. Cytomorphologic analysis showed the presence of round or oval medium-sized and large-sized lymphocytes with features of centrocytes and centroblasts in some foci, with others dominated by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin and scant cytoplasm
Cutaneous Spindle-Cell B-Cell Lymphoma
Smooth muscle actin
Vimentin
Histology
Tumour
Table 1 Histological and immunochemical profile of main differential diagnosis
S100
+/
Rare
Rare
+
CD34
N/A
N/A
+
+/
+
N/A
+/
CD68
Letters to the Editor 1251
© 2015 European Academy of Dermatology and Venereology
Letters to the Editor
1252
well-circumscribed soft tissue lobular mass of 1 cm < 1.2 cm with a smooth surface. After surgical excision, at the gross examination, the lesion was hard, grey and with a pseudocapsule. Histopathological examination and immunochemistry analysis showed morpho-phenotype features of IMT (see Fig. 1 for details). Table 1 reports the main histological differential diagnosis and its immunochemical profile. The lesion was completely removed and after a 6 month clinical and ultrasound follow-up no signs of recurrence were observed. To the best of our knowledge, this case is the first to be reported in the literature involving female genitalia. Because of the rarity of this type of tumour, its nature and behaviour are not yet clear. The clinical course of IMT patients is generally benign after surgical removal of the lesion. Even if rare cases of relapses of extra-pulmonary IMT with local and metastatic aggressive behaviour are rarely reported, none of the reported 19 cases of cutaneous IMT have shown constitutional symptoms, local recurrence, lymph node involvement or malignant behaviour. Although no evidence of compulsory IMT recurrence or malignant transformation has been described, it has been observed that a prolonged follow-up period is necessary after surgical resection of other regions IMT, due to histologic similarity of IMT to certain malignant tumours. Moreover, there is still controversy regarding the pathogenesis: whether it is a reactive process due to some stimulus or it is a true neoplasm.5 Indeed, the aetiology of IMT still remains unknown. Some consider IMT to be an inflammatory, reactive lesion because of its histological findings as mixed inflammatory cells, the lack of atypia in the spindle cells, the polyclonality of the plasma cells and the feature that the stromal cells consist predominantly of myofibroblasts.7 A pathogenetic role of different infectious agents has been proposed, while others insist that IMT is a true neoplasm, because most IMTs were reported to occur spontaneously and in some cases found to have recurrent rearrangement of ALK and monoclonality.8,9 These alterations enhance the hypothesis of a possible neoplastic nature of the lesion, integrating it in the group of “IgG4-related disease”.10
JEADV 2016, 30, 1195–1252
M. Pellegrino,1 L. Feci,1,* P. Taddeucci,1 V. Mancini,2 E. Trovato,1 C. Miracco,2 M. Fimiani1 1 Dermatology Section, Department of Clinical Medicine and Immunological Sciences, 2Pathological Anatomy Section, Department of Human Pathology and Oncology, University of Siena, Siena, Italy *Correspondence: L. Feci. E-mail: [email protected] Financial disclosures: The authors declare that there are no financial or personal relationships that could inappropriately influence (or bias) their decisions, work or manuscript.
References 1 Coffin CM, Fletcher JA. Inflammatory myofibroblastic tumour. In Fletcher CDM, Unni KK, Mertens F eds. World Health Organization Classification of Tambours. Pathology and Genetics of Tumours of Soft Tissue and Bone. IARC Press, Lyon, 2002: 91–93. 2 Coffin CM, Humphrey PA, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological survey. Semin Diagn Pathol 1998; 15: 85–101. 3 Saricaoglu H, Akin S, Adim SB, Karadogan SK. Cutaneous inflammatory pseudotumour. J Eur Acad Dermatol Venereol 2006; 20: 750–751. 4 Pagni F. Cutaneous inflammatory pseudotumor (plasmocytoid granuloma). Pathologica 2007; 99: 84–86. 5 Gonzalez-Vela MC, Val-Bernal JF, Arce FP, Gomez-Roman J, GonzalezLopez MA, Fernandez-Llaca JH. Presence of human herpesvirus-8 in inflammatory myofibroblastic tumor of the skin. J Eur Acad Dermatol Venereol 2007; 21: 399–401. 6 Son SB, Heo YS, Shin WW, Oh TS, Song HJ, Oh CH. A case of cutaneous inflammatory myofibroblastic tumor. Ann Dermatol 2010; 22: 91–95. 7 Jung KH, Kim Y-W, So YK, Choi S-I, Baek MJ. Inflammatory myofibroblastic tumor involving ear lobule. Auris Nasus Larynx 2012; 39: 631–633. 8 Coffin CM, Patel A, Perkins S, Elenitoba-Johnson KS, Perlman E, Griffin CA. ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor. Mod Pathol 2001; 14: 569–576. 9 Su LD, Atayde-Perez A, Sheldon S, Fletcher JA, Weiss SW. Inflammatory myofibroblastic tumor: cytogenetic evidence supporting clonal origin. Mod Pathol 1998; 11: 364–368. 10 Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366: 539–551. DOI: 10.1111/jdv.13184
© 2015 European Academy of Dermatology and Venereology
1250
6 Ishida H, Imai K, Honma K, Tamura S, Imamura T, Ito M et al. GATA2 anomaly and clinical phenotype of a sporadic case of lymphedema, dendritic cell, monocyte, B and NK cell (DCML) deficiency, and myelodysplasia. Eur J Pediatr 2012; 171: 1273–1276. 7 Muszynski MA, Zerbe CS, Holland SM, Kong HH. A woman with warts, leg swelling and deafness. J Am Acad Dermatol 2014; 71: 577–580. DOI: 10.1111/jdv.13183
A case of inflammatory myofibroblastic tumour of the right labium majus Editor Inflammatory myofibroblastic tumour (IMT) is a rare massforming lesion characterized by fibroblastic or myofibroblastic spindle cell proliferations with varying degrees of inflammatory cell infiltration, prevalent lymphocytes, plasma cells and histiocytes.1 The tumour occurs most commonly in the lungs, where
it presents genuinely benign behaviour. Even though rare, extrapulmonary IMTs have been reported mostly in the bladder, mesenteric and mediastinum areas, and is characterized by different, more aggressive behaviour.2 Yet only 18 cases of cutaneous IMT have been reported in the literature.3–7 The clinical presentation of cutaneous IMT is not specific and it varies in size and shape. Patients generally present with a mass but without specific symptoms, so it seldom enters differential diagnosis at the time of the initial evaluation. Recently, we observed a case of cutaneous IMT of the vulva. A 38-year-old woman presented with a small vulvar nodular lesion of the right labium majus. The lesion was reported to have been present for more than 3 years, with asymptomatic growth during this time up to its actual size. On physical examination, the lesion was not visible, whereas it was evidenced by palpation examination. It presented as a round, hard, not pulsating mass of 2 cm diameter, fixed at the near tissues, with the over skin normal for colour and aspect. There were no lymphadenopathies or constitutional symptoms, and the laboratory findings were unremarkable. The preoperative ultrasound examination was not exhaustive, showing a mild vascularized homogeneous and
(a)
(b)
(c)
(d)
Fig. 1 (a) A compact fascicular spindle cells proliferation with variable myxoid and collagenized regions. Presence of lymphoid hyperplasia in the dermis and subcutis, with prevalence of B cells area organized in lymphoid nodules with germinal centre formations. Most of these nodules were neovascularized and with an important infiltrate of immature plasma cells, mainly IgG + (haematoxylin and eosin stain: original magnification, 950). The immunochemistry analysis highlighted the negativity of the lymphoid cells at CD15, CD30 and EMA. The germinal centre formations were colonalized by small T cells CD3+ e BCL2. (b) Furthermore, there was a myofibroblastic proliferation with immunohistochemical cytoplasmic positivity for ALK1 (original magnification, 9100). Using immunohistochemistry, the tumour cells are also positive for p80/ALK1. (c) The spindle cells were negative for S-100 protein (immunohistochemistry for S-100, original magnification, 9200). (d) Staining for smooth muscle actin (SMA) highlighted the spindle cells, confirming their myofibroblastic nature (immunohistochemistry for SMA, original magnification, 9200).
JEADV 2016, 30, 1195–1252
© 2015 European Academy of Dermatology and Venereology
JEADV 2016, 30, 1195–1252
+
Rare
+
+
+
N/A
+
Not contiguous with epithelium; contains pleomorphic histiocytic cells, giant cells with atypical bizarre nuclei. Surrounds without destroying adnexa
Diffusely infiltrative, mildly atypical spindle cells in fascicles within a collagenous/hyalinized/myxoid/stroma. Scattered tumour giant cells, focal lymphocytes and plasma cells mean mitotic rate 2/10HPF, and necrosis
Three patterns: (1) Myxoid, vascular, with inflammatory areas; (2) Compact spindle cells with inflammatory cells; (3) Sparsely cellular with collagen.
Low-grade myofibroblastic sarcoma (myofibrosarcoma)
Extrapulmonary inflammatory myofibroblastic tumour
Atypical fibroxanthoma
+/
+/
Mitotically active; cellular lesion with plump immature fibroblasts in short irregular fascicles with prominent nucleoli
Nodular fasciitis
+/
+
Predominantly myxoid stroma with prominent pleomorphism, stellate or tripolar nuclei may be seen
Myxoid myxofibrosarcoma
Rare
+/
+/
+
Bland spindle cells in whorls and fascicles; fibrous areas alternate with myxoid stroma. Mild pleomorphism with thick collagen bundles
Fibromyxoid sarcoma
+/
Rare
Cytokeratin
N/A
N/A
+/
Rare
+
Epithelial membrane antigen
Immunohistochemical profile Desmin
+
+
Lesion was deeply located within the subcutaneous tissue and consisted of interlacing fascicles of predominant histiocyte-like spindle cells intermingled with pleomorphic giant cells with bizarre large nuclei (bilobed and multilobed) and prominent eosinophilic nucleoli. Prominent hyaline collagen bundles surrounded by tumour cells are usually observed, predominantly at the periphery of the lesion.
Atypical fibrous histiocytoma
+
Diffuse infiltration of the skin and the subcutaneous fatty tissue by densely packed, cytologically relatively uniform, spindle-shaped tumour cells, arranged in a characteristic storiform (mat-like) shape. A typical feature is the spread of tumour cells along the septae of the subcutaneous fatty tissue as well as their diffuse permeation. Fibrosarcomatous DFSP typically appears with an abrupt or gradual transition into cell-rich spindle-cell fascicles with cytological atypia and an increased mitotic figure rate.
Dermatofibrosarcoma protuberans
Nodular or dense diffuse infiltrates involving the entire dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles between the spindled cells were present in one case. Cytomorphologic analysis showed the presence of round or oval medium-sized and large-sized lymphocytes with features of centrocytes and centroblasts in some foci, with others dominated by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin and scant cytoplasm
Cutaneous Spindle-Cell B-Cell Lymphoma
Smooth muscle actin
Vimentin
Histology
Tumour
Table 1 Histological and immunochemical profile of main differential diagnosis
S100
+/
Rare
Rare
+
CD34
N/A
N/A
+
+/
+
N/A
+/
CD68
Letters to the Editor 1251
© 2015 European Academy of Dermatology and Venereology
Letters to the Editor
1252
well-circumscribed soft tissue lobular mass of 1 cm < 1.2 cm with a smooth surface. After surgical excision, at the gross examination, the lesion was hard, grey and with a pseudocapsule. Histopathological examination and immunochemistry analysis showed morpho-phenotype features of IMT (see Fig. 1 for details). Table 1 reports the main histological differential diagnosis and its immunochemical profile. The lesion was completely removed and after a 6 month clinical and ultrasound follow-up no signs of recurrence were observed. To the best of our knowledge, this case is the first to be reported in the literature involving female genitalia. Because of the rarity of this type of tumour, its nature and behaviour are not yet clear. The clinical course of IMT patients is generally benign after surgical removal of the lesion. Even if rare cases of relapses of extra-pulmonary IMT with local and metastatic aggressive behaviour are rarely reported, none of the reported 19 cases of cutaneous IMT have shown constitutional symptoms, local recurrence, lymph node involvement or malignant behaviour. Although no evidence of compulsory IMT recurrence or malignant transformation has been described, it has been observed that a prolonged follow-up period is necessary after surgical resection of other regions IMT, due to histologic similarity of IMT to certain malignant tumours. Moreover, there is still controversy regarding the pathogenesis: whether it is a reactive process due to some stimulus or it is a true neoplasm.5 Indeed, the aetiology of IMT still remains unknown. Some consider IMT to be an inflammatory, reactive lesion because of its histological findings as mixed inflammatory cells, the lack of atypia in the spindle cells, the polyclonality of the plasma cells and the feature that the stromal cells consist predominantly of myofibroblasts.7 A pathogenetic role of different infectious agents has been proposed, while others insist that IMT is a true neoplasm, because most IMTs were reported to occur spontaneously and in some cases found to have recurrent rearrangement of ALK and monoclonality.8,9 These alterations enhance the hypothesis of a possible neoplastic nature of the lesion, integrating it in the group of “IgG4-related disease”.10
JEADV 2016, 30, 1195–1252
M. Pellegrino,1 L. Feci,1,* P. Taddeucci,1 V. Mancini,2 E. Trovato,1 C. Miracco,2 M. Fimiani1 1 Dermatology Section, Department of Clinical Medicine and Immunological Sciences, 2Pathological Anatomy Section, Department of Human Pathology and Oncology, University of Siena, Siena, Italy *Correspondence: L. Feci. E-mail: [email protected] Financial disclosures: The authors declare that there are no financial or personal relationships that could inappropriately influence (or bias) their decisions, work or manuscript.
References 1 Coffin CM, Fletcher JA. Inflammatory myofibroblastic tumour. In Fletcher CDM, Unni KK, Mertens F eds. World Health Organization Classification of Tambours. Pathology and Genetics of Tumours of Soft Tissue and Bone. IARC Press, Lyon, 2002: 91–93. 2 Coffin CM, Humphrey PA, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological survey. Semin Diagn Pathol 1998; 15: 85–101. 3 Saricaoglu H, Akin S, Adim SB, Karadogan SK. Cutaneous inflammatory pseudotumour. J Eur Acad Dermatol Venereol 2006; 20: 750–751. 4 Pagni F. Cutaneous inflammatory pseudotumor (plasmocytoid granuloma). Pathologica 2007; 99: 84–86. 5 Gonzalez-Vela MC, Val-Bernal JF, Arce FP, Gomez-Roman J, GonzalezLopez MA, Fernandez-Llaca JH. Presence of human herpesvirus-8 in inflammatory myofibroblastic tumor of the skin. J Eur Acad Dermatol Venereol 2007; 21: 399–401. 6 Son SB, Heo YS, Shin WW, Oh TS, Song HJ, Oh CH. A case of cutaneous inflammatory myofibroblastic tumor. Ann Dermatol 2010; 22: 91–95. 7 Jung KH, Kim Y-W, So YK, Choi S-I, Baek MJ. Inflammatory myofibroblastic tumor involving ear lobule. Auris Nasus Larynx 2012; 39: 631–633. 8 Coffin CM, Patel A, Perkins S, Elenitoba-Johnson KS, Perlman E, Griffin CA. ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor. Mod Pathol 2001; 14: 569–576. 9 Su LD, Atayde-Perez A, Sheldon S, Fletcher JA, Weiss SW. Inflammatory myofibroblastic tumor: cytogenetic evidence supporting clonal origin. Mod Pathol 1998; 11: 364–368. 10 Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366: 539–551. DOI: 10.1111/jdv.13184
© 2015 European Academy of Dermatology and Venereology
