Fig 1. Numerous atrophic scars on labial and perianalskin along with a superficial perianal ulcer.

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carcinoma. The degree of cellularity, atypia of thecells, mitotic rate, and evidence of vascular orlymphatic invasion can be useful but not definitive.Various markers have been used to ascertain theidentity of these tumors, including ER, PR, S-100,cytokeratins, carcinoembryonic antigen, alpha-lactalbumin, HMFG-1 and -2 (human milk fatglobulins), MUC1, MUC2, EMA (epithelial mem-brane antigen), myoepithelial markers such as p63and smooth muscle actin, podoplanin, GCDFP 15,epidermal growth factor receptor, and E-cadherin,but none is perfect.1-4 A recent report demon-strated that a panel of p63, CK5, CK14, CK17, andmammaglobin had 100% sensitivity and 91% spec-ificity in distinguishing these two.5 However, itincluded only 23 cases and has not been con-firmed by others. Clinically, cutaneous metastasesusually develop rapidly, over a course of weeks tomonths, and there are frequently multiple lesions.Also, although in majority of the cases, a primarytumor can be found in metastases of breast cancer,there have been cases of metastases without aprimary tumor. In conclusion, more research isrequired to further differentiate these entities, andlong-term follow-up is essential in the care of thesepatients.

Lixia Z. Ellis, MD, PhD,a Renata Prado, MD,a

Whitney High, MD, JD, MEng,a,b William A.Robinson, MD, PhD,c and J. Ramsey Mellette,MDa

Departments of Dermatology,a Dermatopathology,b

and the Division of Medical Oncology,c Univer-sity of Colorado, Aurora

Funding sources: None.

Conflicts of interest: None declared.

Correspondence and reprint requests to: Lixia Z.Ellis, MD, PhD, University of Colorado, Depart-ment of Dermatology, 1665 Aurora Ct, Mail StopF703, Aurora, CO 80045-2517.

E-mail: lixia.ellis@ucdenver.edu

REFERENCES

1. Busam KJ, Tan LK, Granter SR, Kohler S, Junkins-Hopkins J,

Berwick M, et al. Epidermal growth factor, estrogen, and

progesterone receptor expression in primary sweat gland

carcinomas and primary and metastatic mammary carcinomas.

Mod Pathol 1999;12:786-93.

2. Acs G, Lawton TJ, Rebbeck TR, LiVolsi VA, Zhang PJ. Differential

expression of E-cadherin in lobular and ductal neoplasms of the

breast and its biologic and diagnostic implications. Am J Clin

Pathol 2001;115:85-98.

3. Zelger BG, Stelzmueller I, Dunst KM, Zelger B. Solid apocrine

carcinoma of the skin: report of a rare adnexal neoplasmmimick-

ing lobular breast carcinoma. J Cutan Pathol 2008;35:332-6.

4. Fernandez-Flores A. Primary cutaneous apocrine carcinoma

versus metastasis, a plea to the dermatopathology community.

Am J Dermatopathol 2010;32:853-4.

5. Rollins-Raval M, Chivukula M, Tseng GC, Jukic D, Dabbs DJ. An

immunohistochemical panel to differentiate metastatic breast

carcinoma to skin from primary sweat gland carcinomas with a

review of the literature. Arch Pathol Lab Med 2011;135:975-83.

http://dx.doi.org/10.1016/j.jaad.2012.01.005

Nasal-type extranodal natural killer/T-celllymphoma presenting as genital ulcers

To the Editor: Primary cutaneous lymphomas of thenatural killer/T-cell subtype (NK/TCL) are extremelyrare. We report the case of a woman with an NK/TCLthat presented as painful genital and perianal ulcers.

A 50-year-old Mexican woman attended our in-stitute complaining of vulvar and perianal ulcers thatinsidiously appeared over an 18-month period.Some resolved in 2- to 6-month intervals whileothers persisted. She had attended several dermatol-ogists, and skin biopsies were performed twicewithout a definitive diagnosis. Her disease hadbeen attributed to a myriad of infections (herpetic,bacterial, fungal) and treated accordingly, withoutsuccess. Upon admission, she presented with severalatrophic scars on labial and perianal skin along witha superficial perianal ulcer, with regular borders andan infiltrated base (Fig 1). A biopsy was performed,showing a pandermal and subcutaneous, angiocen-tric infiltrate with no epidermotropism, which con-sisted of intermediate-sized and large lymphocyteswith hyperchromatic and irregular nuclei (Fig 2,A-C ). Positive immunohistochemical stains for CD2,CD3E (Fig 2, D), CD56 (Fig 2, E ), TIA-1, perforin and

Fig 2. Incisional skin biopsy from the border of the perianal ulcer. A, Hematoxylin-eosinestained (H&E) section (34) showing a diffuse lymphocytic infiltrate in the deepreticular dermis, with focal distribution in the lobules of fat tissue and vascular invasion (smallarrow). B, H&E-stained section (310) displaying the superficial atypical lymphocytic infiltratewith no epidermotropism (arrows). C, H&E-stained section (340) showing pleomorphiclymphocytes with hyperchromatic nuclei and scant neoplasm. D, CD3E-positive dermallymphocytes revealed by immunochemistry (310). Note that there is almost no epidermot-ropism. E, Immunohistochemical identification of CD56-positive cells in the papillary andreticular dermis (310). F, In situ hybridization for Epstein-Barr viruseencoded RNA (EBER)demonstrates abundant expression within most dermal lymphocytes (black dots exemplifiedby small arrows) (310). Note an adjacent sweat gland with no EBER signal (large arrow).

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Granzyme B, along with the detection of the Epstein-Barr viruseencoded small RNA (EBER) by in situhybridization (Fig 2, F ) were consistent with extra-nodal NK/TCL, nasal-type. An exhaustive screeningfor systemic disease failed to demonstrate extracuta-neous disease and nasopharyngeal involvement.The patient received 18 cycles of superficial radio-therapy followed by combination chemotherapyconsisting of 2 cycles of vincristine, prednisone andl-asparaginase. This treatment was subsequentlysubstituted by CHOEP (cyclophosphamide, hydrox-ydaunorubicin, oncovin, etoposide, and predni-sone) because of an episode of transienthypotension. She has recently completed her thirdsession of CHOEP and has no clinically detectabledisease 12 months after beginning her treatment.

Extranodal NK/TCL is mainly reported in LatinAmerica and Asia. It classically affects the upperrespiratory tract, but the skin is the second mostcommon site. It is clinically heterogeneous and

tumors usually appear on the trunk and extremitiesas nonspecific nodules or infiltrated plaques.1

Seven cases involving the female internal genitalorgans have been reported. None concerned thevulva, perineum, or perianal skin.2 Furthermore,the presence of ulcers as the sole primary lesion isexceedingly uncommon.1 The presentation as in-sidious ulcers at external genitalia and perianal skinmake this case unique, since a thorough PubMedsearch failed to identify cases of nasal-type extra-nodal NK/T-cell lymphomas presenting as genitalulcers.

The histological features are the presence ofatypical lymphocytes with angioinvasion, angiodes-truction, and zonal necrosis. These are CD56 posi-tive, with constant Epstein-Barr virus (EBV)expression ( paramount for the diagnosis and imply-ing that it may be crucial in lymphomagenesis),and lack genetic T-cell receptor (TCR)-generearrangements.1

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The clinical course is aggressive and conveys apoor prognosis. Neoplastic cells commonly fail torespond to multiple-agent chemotherapy. The me-dian survival for cases presenting in the skin is lessthan 12 months.1 Positivity to EBV, lymphadenopa-thies, bone marrow or extracutaneous involvement,angiocentrism, panniculitis-like changes, and a highproliferation index have all been associated with apoor prognosis.3-5 In patients with nonhealing gen-ital ulcers, cutaneous lymphoma should be consid-ered in the differential diagnosis.

Yann Charli-Joseph, MD,a Marcela Saeb-Lima,MD,b Amparo Hern�andez-Salazar, MD,a andJudith Dom�ınguez-Cherit, MDa

Departments of Dermatologya and Pathology,b In-stituto Nacional de Ciencias M�edicas y Nutrici�onSalvador Zubir�an, Mexico City, Mexico

Funding sources: None.

Conflicts of interest: None declared.

Correspondence to: Judith Dominguez-Cherit, MD,15 Vasco de Quiroga, Secci�on XVI, Tlalpan,Mexico City, Mexico 16020.

E-mail: judom59@hotmail.com

REFERENCES

1. Chia HY, Tey HL, Tan KB, Chong WS. Nasal-type extranodal

natural killer/T-cell lymphoma presenting with extensive leg

ulcers. Clin Exp Dermatol 2009;34(8):e693-5.

2. Nakamura S, Kato M, Ichimura K, Yatabe Y, Kagami Y, Suzuki R,

et al. Peripheral T/natural killer-cell lymphoma involving the

female genital tract: a clinicopathologic study of 5 cases. Int J

Hematol 2001;73:108-14.

3. Kojima H, Mukai HY, Shinagawa A, Yoshida C, Kamoshita M,

Komeno T, et al. Clinicopathological analyses of 5 Japanese

patients with CD561 primary cutaneous lymphomas. Int J

Hematol 2000;72:477-83.

4. Bekkenk MW, Jansen PM, Meijer CJ, Willemze R. CD561hematological neoplasms presenting in the skin: a retrospec-

tive analysis of 23 new cases and 130 cases from the literature.

Ann Oncol 2004;15(7):1097-108.

5. Kim SJ, Kim BS, Choi CW, Choi J, Kim I, Lee YH, et al. Ki-67

expression is predictive of prognosis in patients with stage I/II

extranodal NK/T-cell lymphoma, nasal type. Ann Oncol

2007;18:1382-7.

http://dx.doi.org/10.1016/j.jaad.2011.12.031

Skin involvement in ALK-negative systemicanaplastic large-cell lymphoma

To the Editor: Primary cutaneous anaplastic large-celllymphoma (ALCL) is usually negative for anaplasticlymphoma kinase (ALK) and usually shows goodclinical prognosis. However, in systemic ALCL, un-like in primary cutaneous ALCL, ALK-negative resultssuggest a poor prognosis.1 We report a case of ALK-

negative systemic ALCL initially presenting as aremarkable skin tumor mimicking primary cutane-ous ALCL.

A 42-year-old woman presented with a 1-monthhistory of a skin tumor on her neck. On physicalexamination, a 4.5 3 3.5 3 2.2-cm, soft, reddishtumor was found on the right side of the neck (Fig 1).The patient also complained of fever and cervicallymphadenopathy. A skin biopsy specimen from thecenter of the tumor displayed dense nodular infil-trate of atypical mononuclear cells from the dermis tothe subcutaneous area (Fig 2, A). These atypical cellsstained positive for CD45RO, CD8, CD30 (Fig 2, B)and granzyme B, but negative for CD3, CD4, CD20,CD56, EBER, and ALK. T-cell receptor C�1 andJ�gene rearrangements were demonstrated bySouthern blotting analysis. Fluorodeoxyglucose-positron emission tomography/computed tomogra-phy (FDG-PET/CT) showed abnormal FDG uptakenot only at the right cervical skin tumor and lymphnode but also at several bones elsewhere in thebody, suggesting the systemic involvement of lym-phoma cells. These findings led to the diagnosis ALK-negative systemic ALCL with skin metastasis. In theDepartment of Hematology, combination chemo-therapy of cyclophosphamide, Adriamycin, vincris-tine, and prednisolone (CHOP) was started. After 3courses of CHOP treatment, the cervical tumordisappeared and complete remission (CR) was con-firmed by FDG-PET/CT. Three additional courses ofCHOP were given, after which high-dose chemo-therapy of ranimustine, carboplatin, etoposide, andcyclophosphamide supported by auto-peripheralblood stem cell transplantation (auto-PBSCT) wasperformed. Eight months have passed in CR.

Skin involvement in systemic ALCL is relativelyrare.2 Recently, Rieger et al3 reported a case of ALK-negative intravascular systemic ALCL in which anenlarging skin lesion led to the diagnosis, which issimilar to how our case was diagnosed. ALK expres-sion is known to be preserved within all involvedlesions of a patient,4 and skin lesions are moreaccessible than other organs; therefore, investigationof ALK status in skin lesions is very useful inevaluating prognosis and making treatment strategy.

Because of the poor prognosis, we chose auto-PBSCT for treatment of this case. Although thebenefit of upfront transplant is not clearly defined,1

long-term outcomes of auto-PBSCT for peripheralT-cell lymphoma including systemic ALCL wereretrospectively analyzed.5 Five-year overall survivalwas significantly higher in patients receiving trans-plant during complete response than in thosereceiving transplant during other disease statuses(71.4% vs 27.3%; P ¼ .046). Although the follow-up