234 Letters to the Editor 6 Cottoni F, Massarelli G, Tedde G, Lissia A. Follicular mucinosis plus mycosis fungoides and acanthosis nigricans plus alveolar bronchiolar carcinoma. Int J Dermatol 1995; 34:867–9. 7 Willemze R, Scheffer E, Van Vloten WA. Mycosis fungoides simulating acanthosis nigricans. Am J Dermatopathol 1985; 7:367–71. 8 Bagot M, Boumsell L, Bensussan A. [Sezary cell]. Hematologie 2002; 8:265–71. (in French).
Funding sources: none. Conflicts of interest: none declared.
Myeloid sarcoma of the vulva as the initial presentation of acute myeloid leukaemia DOI: 10.1111/bjd.14063
Fig 2. Brown palmar pigmentation.
release of TGF-a after chemotherapy-induced tumour cell lysis. Of note, in the cases of MF-associated AN described in the literature, the occurrence of AN did not seem to predict a turning point in the course of the MF. The median time to onset was 56 years (range 3–10 years) after evolution of MF. In conclusion, it should be kept in mind that paraneoplastic AN could also be secondary to cutaneous epidermotropic lymphoma – mainly mycosis fungoides but also Sezary syndrome. Department of Dermatology, Saint-Louis Hospital, Paris, France Correspondence: Jihan Fahmy. E-mail: [email protected]
J. FAHMY M. HALABI-TAWIL C. RAM-WOLFF M. BAGOT A. PETIT
References 1 Krawczyk M, Mykala-Ciesla J, Kolodziej-Jaskula A. Acanthosis nigricans as a paraneoplastic syndrome. Case reports and review of literature. Pol Arch Med Wewn 2009; 119:180–3. 2 Janier M, Blanchet-Bardon C, Bonvalet D et al. Malignant acanthosis nigricans associated with non-Hodgkin’s lymphoma. Report of 2 cases. Dermatologica 1988; 176:133–7. 3 Charli-Joseph Y, Chong K, Ai WZ et al. Paraneoplastic acanthosis nigricans paralleling disease course in a patient with mycosis fungoides. Eur J Dermatol 2013; 23:907–8. 4 Schweitzer WJ, Goldin HM, Bronson DM, Brody PE. Acanthosis nigricans associated with mycosis fungoides. J Am Acad Dermatol 1988; 19:951–3. 5 Neill SM, Monk BE, du Vivier A. Mycosis fungoides associated with acanthosis nigricans. J R Soc Med 1985; 78:79–81. British Journal of Dermatology (2016) 174, pp231–241
DEAR EDITOR, Myeloid sarcomas are rare extramedullary tumours composed of myeloblasts or immature myeloid cells.1,2 They occur most often in the bone, soft tissues, peritoneum, lymph nodes and skin. Involvement of mucosal surfaces is unusual. We describe an exceptional case of myeloid sarcoma occurring on the vulvar mucosa as the presenting sign of acute myeloid leukaemia (AML) following bone marrow transplantation for myelodysplastic syndrome. A 45-year-old woman presented to our dermatological clinic with a rapidly enlarging mass on her vulva for 2 weeks. She denied any systemic symptoms such as fever, lethargy or loss of weight. She had a history of myelodysplastic syndrome, and had received allogeneic haematopoietic stem cell transplantation from her younger brother 7 years earlier. Since then, she had received regular follow-up at our haematology department, and her haematological parameters had remained stable. On physical examination, a 25-cm firm, nontender erythematous nodule was noted on the vulvar mucosa overlying the clitoris (Fig. 1a). An incisional biopsy showed diffuse infiltration of the dermis by medium-sized immature myeloid precursor cells with variable amounts of eosinophilic to amphophilic cytoplasm, large convoluted vesicular nuclei and prominent nucleoli (Fig. 2a, b). There were frequent mitoses. Immunohistochemistry revealed positive reactions with lysozyme, CD43, CD117 and CD56, and negative reactions with myeloperoxidase, terminal deoxynucleotidyl transferase, CD3 and CD20 (Fig. 2c– h). A diagnosis of myeloid sarcoma was made. Two weeks after skin biopsy, she was admitted to our hospital with anuria. On admission, the peripheral blood examination was normal with no leucocytosis, anaemia or thrombocytopenia. However, there was a marked deterioration of renal function (creatinine 529 mg dL1). Abdominal ultrasound showed bilateral hydronephrosis with a nondistended bladder. Computed tomography and magnetic resonance imaging revealed multiple tumours in the bilateral perirenal spaces and bilateral adnexae with encasement of bilateral © 2015 British Association of Dermatologists
Letters to the Editor
(a)
(b)
Fig 1. (a) The patient presented with a rapidly enlarging mass on her vulvar mucosa for 2 weeks. (b) Following chemotherapy there was a marked reduction in the size of the vulvar mass.
ureters. During admission there was a progressive increase in the peripheral blood white blood cell count (rising from 829 9 109 cells L1 on admission to 4498 9 109 cells L1 on day 12) and blast cell percentage (rising from 0% on admission to 765% on day 12). A bone marrow biopsy showed marrow replacement by blast cells of the myeloid series. Cytogenetic study of the bone marrow revealed complex chromosomal abnormalities with t(1;7)(p22;q36) and t(3;21) (q22;q26) and loss of chromosome 16. A diagnosis of AML (M5, acute monocytic leukaemia) was made. The patient underwent bilateral percutaneous nephrostomy insertion, which resulted in improvement of renal function. She subsequently received systemic chemotherapy with cytarabine (for 7 days) and idarubicin (3 days), following which bone marrow and peripheral blood examination showed no blast cells. There was a marked reduction in the size of the vulvar mass (Fig. 1b). However, she developed neutropenic fever and pneumonia after the second course of chemotherapy, and died of septic shock and respiratory failure 3 months after diagnosis of myeloid sarcoma. Myeloid sarcoma is also known as granulocytic sarcoma or chloroma. It can occur in three different clinical settings – in patients with known AML, in patients with myeloproliferative disorder or myelodysplastic syndrome, and in those with no clinical evidence of haematological disease at the © 2015 British Association of Dermatologists
235
time of diagnosis.1,2 The myeloid precursor cells usually stain positively for lysozyme, CD43 and chloroacetate esterase, and may also express myeloperoxidase, CD34 and CD117.1,3 Tumour cells lack antigens specific to T cells (CD3) and B cells (CD20). Cutaneous myeloid sarcomas are more frequently monocytic in origin, and therefore are often negative for myeloperoxidase.1 In our patient, tumour cells also expressed CD56, which has previously been implicated as a possible risk factor for development of myeloid sarcoma.4–6 Involvement of the female genital tract by myeloid sarcoma is an uncommon occurrence. Cases of myeloid sarcoma involving the ovary, cervix, uterus and vagina have previously been documented.7–9 Occurrence on the vulva is exceptional. Previously, Ersßahin et al. described an elderly woman with myeloid sarcoma of the vulva as the initial presentation of AML.10 In contrast to our patient, the tumour in the previous report occurred mainly on the skin of the labia majora, not the vulvar mucosa. Moreover, there was no prior history of myelodysplastic syndrome or other haematological diseases in the previous case. Similarly to our case, the vulvar mass in the previous report regressed following chemotherapy, but the patient died some months later. In summary, we describe an exceptional case of myeloid sarcoma occurring on the vulvar mucosa as the first indication of leukaemic transformation following bone marrow transplantation for myelodysplastic syndrome. We propose that leukaemic infiltration should be suspected in any patient with a history of myeloid leukaemia or myelodysplastic syndrome who presents with a mass involving the skin or external mucosal surface. A high index of suspicion is required even if the haematological disorder has apparently been in prolonged remission following bone marrow transplantation and there has been no clinical evidence of disease relapse for many years, as demonstrated in this case. 1
Department of Dermatology and Department of Pathology, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan 2 Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence: G.-S. Chen. E-mail: [email protected] 3
S.C.-S. HU1,2 W.-T. CHEN3 G.-S. CHEN1,2
References 1 Klco JM, Welch JS, Nguyen TT et al. State of the art in myeloid sarcoma. Int J Lab Hematol 2011; 33:555–65. 2 Campidelli C, Agostinelli C, Stitson R, Pileri SA. Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol 2009; 132:426–37. 3 Pileri SA, Ascani S, Cox MC et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007; 21:340–50. British Journal of Dermatology (2016) 174, pp231–241
236 Letters to the Editor
(a)
(b)
(c)
(d)
(e)
(f)
(g)
(h) Fig 2. (a, b) Skin biopsy showed diffuse infiltration of the dermis by medium-sized immature myeloid precursor cells (haematoxylin–eosin; magnification: a 9 40, b 9 400). (c–h) Immunohistochemical staining revealed positive reactions with lysozyme (c), CD43 (d), CD117 (e) and CD56 (f), and negative reactions with CD3 (g) and CD20 (h) (magnification 9 100).
4 Murakami Y, Nagae S, Matsuishi E et al. A case of CD56 + cutaneous aleukaemic granulocytic sarcoma with myelodysplastic syndrome. Br J Dermatol 2000; 143:587–90. 5 Chang H, Brandwein J, Yi QL et al. Extramedullary infiltrates of AML are associated with CD56 expression, 11q23 abnormalities and inferior clinical outcome. Leuk Res 2004; 28:1007–11. 6 Kurata H, Okukubo M, Fukuda E et al. Myeloid markers should be undertaken in cases of CD56 positivity to exclude granulocytic sarcoma. Br J Dermatol 2002; 147:609–11. 7 Wang X, Liu H, Wu Z et al. A case of acute promyelocytic leukemia presenting with a nonleukemic granulocytic sarcoma of the ovary, with subsequent development of acute myeloid leukemia associated with t(8;21). Leuk Res 2009; 33:580–2. 8 Gill H, Loong F, Mak V et al. Myeloid sarcoma of the uterine cervix presenting as missed abortion. Arch Gynecol Obstet 2012; 286:1339–41. British Journal of Dermatology (2016) 174, pp231–241
9 Policarpio-Nicolas ML, Valente PT, Aune GJ, Higgins RA. Isolated vaginal myeloid sarcoma in a 16-year-old girl. Ann Diagn Pathol 2012; 16:374–9. 10 Ersßahin C, Omeroglu G, Potkul RK, Salhadar A. Myeloid sarcoma of the vulva as the presenting symptom in a patient with acute myeloid leukemia. Gynecol Oncol 2007; 106:259–61.
Funding sources: This work was supported by grants from the Ministry of Science and Technology, Taiwan (103-2314-B037-031-, 104-2314-B-037-048-MY3).
Conflicts of interest: none declared.
© 2015 British Association of Dermatologists
Funding sources: none. Conflicts of interest: none declared.
Myeloid sarcoma of the vulva as the initial presentation of acute myeloid leukaemia DOI: 10.1111/bjd.14063
Fig 2. Brown palmar pigmentation.
release of TGF-a after chemotherapy-induced tumour cell lysis. Of note, in the cases of MF-associated AN described in the literature, the occurrence of AN did not seem to predict a turning point in the course of the MF. The median time to onset was 56 years (range 3–10 years) after evolution of MF. In conclusion, it should be kept in mind that paraneoplastic AN could also be secondary to cutaneous epidermotropic lymphoma – mainly mycosis fungoides but also Sezary syndrome. Department of Dermatology, Saint-Louis Hospital, Paris, France Correspondence: Jihan Fahmy. E-mail: [email protected]
J. FAHMY M. HALABI-TAWIL C. RAM-WOLFF M. BAGOT A. PETIT
References 1 Krawczyk M, Mykala-Ciesla J, Kolodziej-Jaskula A. Acanthosis nigricans as a paraneoplastic syndrome. Case reports and review of literature. Pol Arch Med Wewn 2009; 119:180–3. 2 Janier M, Blanchet-Bardon C, Bonvalet D et al. Malignant acanthosis nigricans associated with non-Hodgkin’s lymphoma. Report of 2 cases. Dermatologica 1988; 176:133–7. 3 Charli-Joseph Y, Chong K, Ai WZ et al. Paraneoplastic acanthosis nigricans paralleling disease course in a patient with mycosis fungoides. Eur J Dermatol 2013; 23:907–8. 4 Schweitzer WJ, Goldin HM, Bronson DM, Brody PE. Acanthosis nigricans associated with mycosis fungoides. J Am Acad Dermatol 1988; 19:951–3. 5 Neill SM, Monk BE, du Vivier A. Mycosis fungoides associated with acanthosis nigricans. J R Soc Med 1985; 78:79–81. British Journal of Dermatology (2016) 174, pp231–241
DEAR EDITOR, Myeloid sarcomas are rare extramedullary tumours composed of myeloblasts or immature myeloid cells.1,2 They occur most often in the bone, soft tissues, peritoneum, lymph nodes and skin. Involvement of mucosal surfaces is unusual. We describe an exceptional case of myeloid sarcoma occurring on the vulvar mucosa as the presenting sign of acute myeloid leukaemia (AML) following bone marrow transplantation for myelodysplastic syndrome. A 45-year-old woman presented to our dermatological clinic with a rapidly enlarging mass on her vulva for 2 weeks. She denied any systemic symptoms such as fever, lethargy or loss of weight. She had a history of myelodysplastic syndrome, and had received allogeneic haematopoietic stem cell transplantation from her younger brother 7 years earlier. Since then, she had received regular follow-up at our haematology department, and her haematological parameters had remained stable. On physical examination, a 25-cm firm, nontender erythematous nodule was noted on the vulvar mucosa overlying the clitoris (Fig. 1a). An incisional biopsy showed diffuse infiltration of the dermis by medium-sized immature myeloid precursor cells with variable amounts of eosinophilic to amphophilic cytoplasm, large convoluted vesicular nuclei and prominent nucleoli (Fig. 2a, b). There were frequent mitoses. Immunohistochemistry revealed positive reactions with lysozyme, CD43, CD117 and CD56, and negative reactions with myeloperoxidase, terminal deoxynucleotidyl transferase, CD3 and CD20 (Fig. 2c– h). A diagnosis of myeloid sarcoma was made. Two weeks after skin biopsy, she was admitted to our hospital with anuria. On admission, the peripheral blood examination was normal with no leucocytosis, anaemia or thrombocytopenia. However, there was a marked deterioration of renal function (creatinine 529 mg dL1). Abdominal ultrasound showed bilateral hydronephrosis with a nondistended bladder. Computed tomography and magnetic resonance imaging revealed multiple tumours in the bilateral perirenal spaces and bilateral adnexae with encasement of bilateral © 2015 British Association of Dermatologists
Letters to the Editor
(a)
(b)
Fig 1. (a) The patient presented with a rapidly enlarging mass on her vulvar mucosa for 2 weeks. (b) Following chemotherapy there was a marked reduction in the size of the vulvar mass.
ureters. During admission there was a progressive increase in the peripheral blood white blood cell count (rising from 829 9 109 cells L1 on admission to 4498 9 109 cells L1 on day 12) and blast cell percentage (rising from 0% on admission to 765% on day 12). A bone marrow biopsy showed marrow replacement by blast cells of the myeloid series. Cytogenetic study of the bone marrow revealed complex chromosomal abnormalities with t(1;7)(p22;q36) and t(3;21) (q22;q26) and loss of chromosome 16. A diagnosis of AML (M5, acute monocytic leukaemia) was made. The patient underwent bilateral percutaneous nephrostomy insertion, which resulted in improvement of renal function. She subsequently received systemic chemotherapy with cytarabine (for 7 days) and idarubicin (3 days), following which bone marrow and peripheral blood examination showed no blast cells. There was a marked reduction in the size of the vulvar mass (Fig. 1b). However, she developed neutropenic fever and pneumonia after the second course of chemotherapy, and died of septic shock and respiratory failure 3 months after diagnosis of myeloid sarcoma. Myeloid sarcoma is also known as granulocytic sarcoma or chloroma. It can occur in three different clinical settings – in patients with known AML, in patients with myeloproliferative disorder or myelodysplastic syndrome, and in those with no clinical evidence of haematological disease at the © 2015 British Association of Dermatologists
235
time of diagnosis.1,2 The myeloid precursor cells usually stain positively for lysozyme, CD43 and chloroacetate esterase, and may also express myeloperoxidase, CD34 and CD117.1,3 Tumour cells lack antigens specific to T cells (CD3) and B cells (CD20). Cutaneous myeloid sarcomas are more frequently monocytic in origin, and therefore are often negative for myeloperoxidase.1 In our patient, tumour cells also expressed CD56, which has previously been implicated as a possible risk factor for development of myeloid sarcoma.4–6 Involvement of the female genital tract by myeloid sarcoma is an uncommon occurrence. Cases of myeloid sarcoma involving the ovary, cervix, uterus and vagina have previously been documented.7–9 Occurrence on the vulva is exceptional. Previously, Ersßahin et al. described an elderly woman with myeloid sarcoma of the vulva as the initial presentation of AML.10 In contrast to our patient, the tumour in the previous report occurred mainly on the skin of the labia majora, not the vulvar mucosa. Moreover, there was no prior history of myelodysplastic syndrome or other haematological diseases in the previous case. Similarly to our case, the vulvar mass in the previous report regressed following chemotherapy, but the patient died some months later. In summary, we describe an exceptional case of myeloid sarcoma occurring on the vulvar mucosa as the first indication of leukaemic transformation following bone marrow transplantation for myelodysplastic syndrome. We propose that leukaemic infiltration should be suspected in any patient with a history of myeloid leukaemia or myelodysplastic syndrome who presents with a mass involving the skin or external mucosal surface. A high index of suspicion is required even if the haematological disorder has apparently been in prolonged remission following bone marrow transplantation and there has been no clinical evidence of disease relapse for many years, as demonstrated in this case. 1
Department of Dermatology and Department of Pathology, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan 2 Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence: G.-S. Chen. E-mail: [email protected] 3
S.C.-S. HU1,2 W.-T. CHEN3 G.-S. CHEN1,2
References 1 Klco JM, Welch JS, Nguyen TT et al. State of the art in myeloid sarcoma. Int J Lab Hematol 2011; 33:555–65. 2 Campidelli C, Agostinelli C, Stitson R, Pileri SA. Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol 2009; 132:426–37. 3 Pileri SA, Ascani S, Cox MC et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007; 21:340–50. British Journal of Dermatology (2016) 174, pp231–241
236 Letters to the Editor
(a)
(b)
(c)
(d)
(e)
(f)
(g)
(h) Fig 2. (a, b) Skin biopsy showed diffuse infiltration of the dermis by medium-sized immature myeloid precursor cells (haematoxylin–eosin; magnification: a 9 40, b 9 400). (c–h) Immunohistochemical staining revealed positive reactions with lysozyme (c), CD43 (d), CD117 (e) and CD56 (f), and negative reactions with CD3 (g) and CD20 (h) (magnification 9 100).
4 Murakami Y, Nagae S, Matsuishi E et al. A case of CD56 + cutaneous aleukaemic granulocytic sarcoma with myelodysplastic syndrome. Br J Dermatol 2000; 143:587–90. 5 Chang H, Brandwein J, Yi QL et al. Extramedullary infiltrates of AML are associated with CD56 expression, 11q23 abnormalities and inferior clinical outcome. Leuk Res 2004; 28:1007–11. 6 Kurata H, Okukubo M, Fukuda E et al. Myeloid markers should be undertaken in cases of CD56 positivity to exclude granulocytic sarcoma. Br J Dermatol 2002; 147:609–11. 7 Wang X, Liu H, Wu Z et al. A case of acute promyelocytic leukemia presenting with a nonleukemic granulocytic sarcoma of the ovary, with subsequent development of acute myeloid leukemia associated with t(8;21). Leuk Res 2009; 33:580–2. 8 Gill H, Loong F, Mak V et al. Myeloid sarcoma of the uterine cervix presenting as missed abortion. Arch Gynecol Obstet 2012; 286:1339–41. British Journal of Dermatology (2016) 174, pp231–241
9 Policarpio-Nicolas ML, Valente PT, Aune GJ, Higgins RA. Isolated vaginal myeloid sarcoma in a 16-year-old girl. Ann Diagn Pathol 2012; 16:374–9. 10 Ersßahin C, Omeroglu G, Potkul RK, Salhadar A. Myeloid sarcoma of the vulva as the presenting symptom in a patient with acute myeloid leukemia. Gynecol Oncol 2007; 106:259–61.
Funding sources: This work was supported by grants from the Ministry of Science and Technology, Taiwan (103-2314-B037-031-, 104-2314-B-037-048-MY3).
Conflicts of interest: none declared.
© 2015 British Association of Dermatologists
