||79-year-old woman presented with a 8-month history of purpuric nodules on the face and trunk. The entire dermis showed dense infiltrate of medium to large mononuclear cells with pleomorphic cleaved nuclei. There is clear subepidermal zone. The neoplastic cells are strongly immunoreactive for LCA and CD43. Many cells are positive for CD3. A few cells showed positivity for Tdt.
Face and trunk
A 79-year-old retired dulang washer presented with 8-month history of mildly pruritic purpuric nodules and plaques on the face, and trunk. It started on the back and subsequently involved the nose and the cheek. It is occasionally pruritic. There was no fever. Her medical history included hypertension and ischemic heart disease and was on propranolol, verapamil and isosorbide nitrate. Hydrochlorothiazide was withheld since the nodules were noted. She had 9 children and stayed in Cameron Highlands.
Dulang (wooden tray) washing of tin ore was a common livelihood of poor women during the post World War II days in Perak, clearing the tin mineral from the sand impurities at the river bank. It is hardly enough to supplement the family's income.
Examination of the skin showed multiple purpuric nodules and plaques of varying size, some about 4 x 3 cm on the nose, right cheek, forehead, right upper back and pre sacral areas. There was no hepatosplenomegaly. No lymphadenopathy.
Multiple purpuric nodules and plaques on the nose, right side of the face, and right upper back.
Hb 15.2 g%
TWBC 9600 (N53%, L33%, M8%, E5%, B1%)
Platelets 153 000
ESR 2 mm/hr
Blood chemistry normal
Abdominal ultrasound scan normal
Biopsy skin: The entire dermis showed dense infiltrate of medium to large mononuclear cells with pleomorphic cleaved nuclei. There is clear subepidermal zone. The epidermis is atrophied.
Immunohistochemistry: The neoplastic cells are strongly immunoreactive for LCA and CD43. Many cells are positive for CD3. A few cells showed positivity for Tdt. They are negative for CD20, CD57, aCD30 and ALK-1 protein.
(LCA: leukocyte common antigen; Tdt: terminal deoxynucleotidyl transferase)
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Cutaneous T-cell lymphoma - Mycosis fungoides (D'emblee variant)?
|Reason for presentation
Skin biopsy with appropriate immunohistochemical staining is the key to diagnosing (aleukemic) leukemia cutis, or lymphoma cutis.
Typical skin findings in leukemic cutis/lymphoma cutis : a Grenz (uninvolved dermis) zone separates the neoplastic infiltrate from the epidermis. The neoplastic infiltrate often shows single filing between collagen bundles and nodular infiltrates around vessels and adnexal structures.
Diffuse expression of CD43, LCA/CD45 and absence of CD20 and CD30 implicates leukemia cutis or blastic NK (CD4+CD56+ hematodermic) lymphoma (plasmacytoid cell neoplasm). Regional CD3 staining could represent tumor infiltrating lymphocytes or T cell lymphoma. Therefore, additional immunohistochemistry is required to more accurately classify this neoplastic process. These antibodies would include CD4, CD56, CD68, and myeloperoxidase.
What is your diagnosis?
What further tests would you do?
How would you treat this patient?
Adrienne Rencic. Leukemia Cutis. Emedicine series. Dermatology (http://emedicine.medscape.com/article/1097702-overview)
Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions.
The dermatologist is instrumental in the diagnosis of leukemia cutis. Accurate diagnosis has tremendous prognostic significance and may establish a diagnosis in cases in which leukemia cutis is the harbinger of a systemic leukemic process. This is called aleukemic leukemia cutis. Additionally, a diagnosis of leukemia cutis portends a poor prognosis and strongly correlates with additional sites of extramedullary involvement. This can alter the appropriate treatment regimen for a patient.
Schwartz, R. Cutaneous T cell lymphoma. Emedicine series - Dermatology
Cutaneous T-cell lymphomas (CTCLs) are the largest group of cutaneous lymphomas, representing 65% of all cutaneous lymphomas. The World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) classification (WHO-EORTC classification) is used to categorize CTCLs. However, a substantial subset of T-cell primary cutaneous lymphomas remains that cannot be classified beyond the unspecified peripheral T-cell category, some of which may have an aggressive course.
Mature T-cell and natural killer (NK) cell neoplasms according to the WHO-EORTC classification are as follows:
- Mycosis fungoides
- Variants of mycosis fungoides (MF)
- Pagetoid reticulosis (localized disease)
- Follicular, syringotropic, granulomatous variant
- Subtype of MF - Granulomatous slack skin (GSS) syndrome
- Sézary syndrome
- CD30+ T-cell lymphoproliferative disorders of the skin
- Lymphomatoid papulosis
- Primary cutaneous anaplastic large cell lymphoma
- Subcutaneous panniculitislike T-cell lymphoma
- Primary cutaneous peripheral T-cell lymphoma (PTL), unspecified
- Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma (provisional)
- Cutaneous gamma/delta-positive T-cell lymphoma (CGD-TCL) (provisional)
- Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (provisional)
- Extranodal NK/T-cell lymphoma, nasal type
- Variant - Hydroa vacciniformialike lymphoma
- Adult T-cell leukemia/lymphoma
- Angioimmunoblastic T-cell lymphoma
Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol. 2008 Jan; 129(1):130-42.
Leukemia cutis (LC) is a nonspecific term used for cutaneous manifestations of any type of leukemia. LC has a wide range of cutaneous manifestations, which can make it difficult to clinically distinguish LC from other skin lesions. Patients with LC usually have concomitant systemic leukemia, but occasionally skin involvement precedes the involvement of the bone marrow or peripheral blood. Thus, a skin biopsy can be the first indication of the presence of leukemia in a subset of patients.
The immunophenotyping of routinely processed skin biopsy specimens is very useful in establishing the diagnosis of LC. Although the molecular mechanisms explaining the pathogenesis of LC are not well defined, chemokine receptors and adhesion molecules may have an important role in skin tropism.
We review the literature and recent advances pertaining to LC, with special emphasis on the immunohistochemical assessment and possible mechanisms involved in skin tropism by leukemic cells.
cutaneous T cell lymphoma, leukemia cutis, leukocyte common antigen, CD43, Tdt
|Comments from Faculty and Members
Robert Rudolph MD, FACP. Clinical Professor of Dermatology, University of Pennsylvania, Philadelphia, PA, USA on September 23, 2009
If one has never seen "the plum colored nodules" of MF or leukemia, here are splendid examples. She needs a full workup, and close follow up. If negative, then "light radiation" would be useful to melt the lesions away.
Tony Petrella M.D. Centre de Pathologie, Dijon, France on September 23, 2009
In my experience, when CD3 and CD20 are negative in a skin lesion like that we must always suspect a skin localisation of a myelomonocytic proliferation or a
plasmacytoid dendritic cell neoplasm
( PDC neoplasm). A bone marrow aspirate is required to look for myelodysplasia and/or blastic infiltration. Even if the case is CD4 and CD56 positive, we need specific antigens such as CD303, CD123, CD2AP and less specific such as TCL1 and bcl11a to confirm a PDC neoplasm. It's also important to look for peripheral monocytosis and lysosyme dosage because such lesion can sometimes be the first clinical manifestation of CMML.
Sam Moshella MD, Clinical Professor of Dermatology, Emeritus, Harvard Medical School, Boston, USA on September 24, 2009
I agree additional immunochemistry studies under the auspices of a hematologic oriented pathologist is necessary to more accurately classify the pathologic process.
Arash Abtahian MD, Resident, Shiraz, Iran on September 25, 2009
Good case. In order to have malignancies in such cases, B cell lymphomas may have such clinical presentations but having the Ags in mind the most probable diagnosis is leukemia cutis as such tumid lesions are seen less in CTCL.
Nick Mihas MD, Greece on October 17, 2009
Very interesting case. The pictures are characteristic.
Tony Petrella M.D. Centre de Pathologie, Dijon, France on October 23, 2009
Here are the results of the immunohistochemical studies. (some pictures attached):
CD68 (clone KP1 1/400) positive (dots)
CD3 (clone SP7 1/100) negative or faintly positive
CD4 (clone NCL-CD4-368 1/20) positive
CD56 (clone NCL-CD56-1B6 1/50) positive
CD 123 (clinisciences, clone 6H6, 1/50) positive
CD303 (BDCA2) (Dendritics, clone 124B-3-13, 1/50) positive
TCL 1 (Dr Teilell, Los Angeles) positive
CD2AP (Dr Mason, Oxford) negative
These results confirm the diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (former CD4/CD56 hematodermic neoplasm).
CD 68 positive
CD 4 positive
CD 56 positive
CD 303 positive
CD 123 positive