CLINICAL PATHOLOGIC CHALLENGE ANSWER
An Ulceration of the Glans Penis Simon A. Ritchie, MD,* Michael P. Lee, MD,† Grace F. Kao, MD,* and Anthony A. Gaspari, MD*
(Am J Dermatopathol 2015;37:585–585)
(Continued from page 544)
ANSWER Acute myelomonocytic leukemia cutis was diagnosed.
DISCUSSION Leukemia cutis is not uncommon in patients with leukemia, especially acute myelomonocytic leukemia,1 but infiltration of the penis does seem to be a rare event, with few cases reported in the literature.2–8 This entity is important due to the differential diagnosis of the lesion and also because it may be the patient’s sole presenting symptom for AML. As in this patient, the cutaneous lesions of AML are commonly asymptomatic and when present on the penis may have an appearance similar to a chancre, the primary lesion of syphilis. This was the first suspected diagnosis in this patient but was less likely given the fact that there was a similar lesion adjacent to the current lesion that was healing spontaneously. Although chancres commonly heal on their own before entering a quiescent period, followed thereafter by secondary syphilis, it would be uncommon for a second primary chancre to arise adjacent to one that has healed. This cycle of ulceration and self-healing is more characteristic of leukemia cutis. Other diagnoses in the differential include chancroid, herpes simplex, granuloma inguinale, invasive squamous cell carcinoma, deep mycotic infection, and factitial dermatitis. An additional diagnosis to consider in a patient with various lymphoproliferative disorders (such as chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute monocytic leukemia, mantle-cell lymphoma, large cell lymphoma, and myelofibrosis, or other immunosuppressive conditions such as human immunodeficiency virus infection) would be an exaggerated arthropod bite reaction. The histological features of leukemia cutis are well demonstrated in the biopsy specimen. A diffuse dermal infiltrate of monomorphic, immature blast cells, with hyperchromatic, ovoid to irregularly shaped nuclei, From the *Department of Dermatology; and †Department of Pathology, University of Maryland, Baltimore, Maryland. There were no sources of funding for this publication. The authors declare no conflicts of interest. Reprints: Simon A. Ritchie, MD, 419 W Redwood St, Suite 240, Baltimore, MD 21201 (e-mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Am J Dermatopathol Volume 37, Number 7, Month 2015
occasional indentation, abundant pale-staining to granular cytoplasm, scattered mitoses, and immature eosinophilic cells is seen (Fig. 2). In addition, tumor cells infiltrate around vascular channels (Figs. 3 and 4 ). CD68 (Fig. 5) and myeloperoxidase (Fig. 6) immunostains confirm the myelomonocytic lineage of the tumor cells, which are identical to those seen in a previous bone marrow biopsy from this patient (Fig. 7). The microscopic features present in the specimens from this patient that distinguish leukemia cutis from an exaggerated arthropod bite reaction associated with a hematopoeitic blast-like cellular response are: sheets of predominantly monomorphic, immature cells in the infiltrate, and staining diffusely positive for myeloperoxidase and CD68 immunostains. In arthropod bite reactions, the cellular infiltrate is polymorphic, including a blast-like, atypical, reactive lymphohistiocytic infiltrate with plasma cells in a background of eosinophilia.9 Leukemia cutis has often been associated with an aggressive disease course, but a significant difference in survival in leukemia patients with leukemia cutis compared with those without is yet to be formally substantiated.1 It has also been noted that disease remission may be shorter in patients with leukemia cutis and therefore warrants aggressive treatment due to higher risk of extramedullary relapses of the leukemia.10 The treatment of leukemia cutis should be directed at the underlying leukemia, which is usually accomplished with the initiation of chemotherapy. Radiotherapy and/or total skin electron beam therapy may also be required as adjuvant treatment.10 REFERENCES 1. Agis H, Weltermann A, Fonatsch C, et al. A comparative study on demographic, hematological, and cytogenetic findings and prognosis in acute myeloid leukemia with and without leukemia cutis. Ann Hematol. 2002;81:90–95. 2. Arias-Santiago S, Aneiros-Fernandez J, Arrabal-Polo MA, et al. Cutaneous plasmacytoma and leukemia cutis on the penis. Eur J Dermatol. 2011;21:107–109. 3. Begun FP, Derus J, Toorkey B, et al. Leukemia of the penis. J Urol. 1989;142:123–124. 4. Chaux A, Amin M, Cubilla AL, et al. Metastatic tumors to the penis: a report of 17 cases and review of the literature. Int J Surg Pathol. 2010;19:597–606. 5. Czarnecki DB, O’Brien TJ, Rotstein H, et al. Leukaemia cutis mimicking primary syphilis. Acta Derm Venereol. 1981;61:368–369. 6. Johnston JH, Levin HM. Leukemic ulcer of the penis. AMA Arch Derm. 1956;74:428–429. 7. Knight EL Jr, Sinha PP, Post GJ, et al. Leukemic infiltration of penis. Urology. 1979;14:83–84. 8. Hsiao LT, Yang CF, Tzeng CH. Penis: a ‘sanctuary’ site of extramedullary leukemia relapse. Int J Hematol. 2009;90:125–126. 9. Barzilai A, Shpiro D, Goldberg I, et al. Insect bite-like reaction in patients with hematologic malignant neoplasms. Arch Dermatol. 1999;135:1503–1507. 10. Bakst RL, Tallman MS, Douer D, et al. How I treat extramedullary acute myeloid leukemia. Blood. 2011;118:3785–3793.
www.amjdermatopathology.com |
585
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
An Ulceration of the Glans Penis Simon A. Ritchie, MD,* Michael P. Lee, MD,† Grace F. Kao, MD,* and Anthony A. Gaspari, MD*
(Am J Dermatopathol 2015;37:585–585)
(Continued from page 544)
ANSWER Acute myelomonocytic leukemia cutis was diagnosed.
DISCUSSION Leukemia cutis is not uncommon in patients with leukemia, especially acute myelomonocytic leukemia,1 but infiltration of the penis does seem to be a rare event, with few cases reported in the literature.2–8 This entity is important due to the differential diagnosis of the lesion and also because it may be the patient’s sole presenting symptom for AML. As in this patient, the cutaneous lesions of AML are commonly asymptomatic and when present on the penis may have an appearance similar to a chancre, the primary lesion of syphilis. This was the first suspected diagnosis in this patient but was less likely given the fact that there was a similar lesion adjacent to the current lesion that was healing spontaneously. Although chancres commonly heal on their own before entering a quiescent period, followed thereafter by secondary syphilis, it would be uncommon for a second primary chancre to arise adjacent to one that has healed. This cycle of ulceration and self-healing is more characteristic of leukemia cutis. Other diagnoses in the differential include chancroid, herpes simplex, granuloma inguinale, invasive squamous cell carcinoma, deep mycotic infection, and factitial dermatitis. An additional diagnosis to consider in a patient with various lymphoproliferative disorders (such as chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute monocytic leukemia, mantle-cell lymphoma, large cell lymphoma, and myelofibrosis, or other immunosuppressive conditions such as human immunodeficiency virus infection) would be an exaggerated arthropod bite reaction. The histological features of leukemia cutis are well demonstrated in the biopsy specimen. A diffuse dermal infiltrate of monomorphic, immature blast cells, with hyperchromatic, ovoid to irregularly shaped nuclei, From the *Department of Dermatology; and †Department of Pathology, University of Maryland, Baltimore, Maryland. There were no sources of funding for this publication. The authors declare no conflicts of interest. Reprints: Simon A. Ritchie, MD, 419 W Redwood St, Suite 240, Baltimore, MD 21201 (e-mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Am J Dermatopathol Volume 37, Number 7, Month 2015
occasional indentation, abundant pale-staining to granular cytoplasm, scattered mitoses, and immature eosinophilic cells is seen (Fig. 2). In addition, tumor cells infiltrate around vascular channels (Figs. 3 and 4 ). CD68 (Fig. 5) and myeloperoxidase (Fig. 6) immunostains confirm the myelomonocytic lineage of the tumor cells, which are identical to those seen in a previous bone marrow biopsy from this patient (Fig. 7). The microscopic features present in the specimens from this patient that distinguish leukemia cutis from an exaggerated arthropod bite reaction associated with a hematopoeitic blast-like cellular response are: sheets of predominantly monomorphic, immature cells in the infiltrate, and staining diffusely positive for myeloperoxidase and CD68 immunostains. In arthropod bite reactions, the cellular infiltrate is polymorphic, including a blast-like, atypical, reactive lymphohistiocytic infiltrate with plasma cells in a background of eosinophilia.9 Leukemia cutis has often been associated with an aggressive disease course, but a significant difference in survival in leukemia patients with leukemia cutis compared with those without is yet to be formally substantiated.1 It has also been noted that disease remission may be shorter in patients with leukemia cutis and therefore warrants aggressive treatment due to higher risk of extramedullary relapses of the leukemia.10 The treatment of leukemia cutis should be directed at the underlying leukemia, which is usually accomplished with the initiation of chemotherapy. Radiotherapy and/or total skin electron beam therapy may also be required as adjuvant treatment.10 REFERENCES 1. Agis H, Weltermann A, Fonatsch C, et al. A comparative study on demographic, hematological, and cytogenetic findings and prognosis in acute myeloid leukemia with and without leukemia cutis. Ann Hematol. 2002;81:90–95. 2. Arias-Santiago S, Aneiros-Fernandez J, Arrabal-Polo MA, et al. Cutaneous plasmacytoma and leukemia cutis on the penis. Eur J Dermatol. 2011;21:107–109. 3. Begun FP, Derus J, Toorkey B, et al. Leukemia of the penis. J Urol. 1989;142:123–124. 4. Chaux A, Amin M, Cubilla AL, et al. Metastatic tumors to the penis: a report of 17 cases and review of the literature. Int J Surg Pathol. 2010;19:597–606. 5. Czarnecki DB, O’Brien TJ, Rotstein H, et al. Leukaemia cutis mimicking primary syphilis. Acta Derm Venereol. 1981;61:368–369. 6. Johnston JH, Levin HM. Leukemic ulcer of the penis. AMA Arch Derm. 1956;74:428–429. 7. Knight EL Jr, Sinha PP, Post GJ, et al. Leukemic infiltration of penis. Urology. 1979;14:83–84. 8. Hsiao LT, Yang CF, Tzeng CH. Penis: a ‘sanctuary’ site of extramedullary leukemia relapse. Int J Hematol. 2009;90:125–126. 9. Barzilai A, Shpiro D, Goldberg I, et al. Insect bite-like reaction in patients with hematologic malignant neoplasms. Arch Dermatol. 1999;135:1503–1507. 10. Bakst RL, Tallman MS, Douer D, et al. How I treat extramedullary acute myeloid leukemia. Blood. 2011;118:3785–3793.
www.amjdermatopathology.com |
585
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
