- lipoid histiocytoma / fibroxanthoma : a type of xanthoma containing fibromatous elements; it is sometimes described as synonymous with or a subtype of either benign or malignant fibrous histiocytoma.
- atypical fibroxanthoma (AFX) : a small nodular cutaneous neoplasm usually occurring on sun-exposed areas of the face and neck in older white adults; it contains cells resembling histiocytes and fibroblasts
- benign fibrous histiocytoma / fibrous xanthoma : any of a group of benign neoplasms occurring in the dermis and characterized by histiocytes and fibroblasts. Classification of these tumors is variable; the term sometimes encompasses several types of neoplasms, such as
-
histiocytoma cutis
/ dermatofibroma / fibrous histiocytoma
-
nodular
subepidermal fibrosis
-
sclerosing
hemangioma
-
malignant fibrous histiocytoma
: any of a group of malignant neoplasms containing cells that resemble
histiocytes and fibroblasts, occurring predominantly in soft tissues in
middle-aged adults; depending on the tumor location and the classification
system, the term is sometimes used synonymously with or as a general term
including similar lesions such as atypical
fibroxanthoma and dermatofibrosarcoma
protuberans.
The group is usually divided into 5 histological subtypes :
- angiomatoid malignant fibrous histiocytoma
- giant cell malignant fibrous histiocytoma
- inflammatory malignant fibrous histiocytoma
- myxoid malignant fibrous histiocytoma
- storiform-pleomorphic malignant fibrous histiocytoma
- histiocytomatosis : any generalized disorder of the reticuloendothelial system, such as
-
xanthomatosis
-
Gaucher disease
-
Niemann-Pick
disease
- lymphogranulomatosis
leukemia/lymphoma"ref
: initially described by Brody et al in 1995ref.
In the WHO classification, blastic NK-cell lymphoma was included
as a clinically aggressive neoplasm with a high incidence of cutaneous
involvement and risk of leukemic dissemination. The blastic cytologic appearance
and CD56 expression initially suggested an NK-precursor origin (Jaffe ES,
Harris NL, Stein H, Vardiman JW (Eds). World Health Organization Classification
of Tumors: Pathology and Genetics of Tumours of Hematopoietic and Lymphoid
Tissues. Lyon, France: IARC Press;2001). More recent studies suggest derivation
from a plasmacytoid dendritic cell precursorref1,
ref2Symptoms & signs : CD4+/CD56+ hematodermic neoplasm commonly presents in the skin with solitary or multiple nodules or tumors with or without concurrent extracutaneous localizationsref1, ref2, ref3, ref4, ref5. About 50% of the patients have nodal or bone marrow involvement at presentationref1, ref2. Most patients presenting with only primary cutaneous nodules (83%) rapidly develop involvement of bone marrow (87%ref), peripheral blood, lymph nodes, and extranodal sites such as spleen (61%)ref1, ref2. CD4+/CD56+ hematodermic neoplasm should be differentiated above all from myelomonocytic leukemia cutis
,
and are conceptually similar to so-called "aleukemic leukemia cutis"ref.
CD4+/CD56+ hematodermic neoplasm (blastic NK-cell
lymphoma). (A) Presentation with large tumor on the back. (B) Monotonous
infiltration of medium-sized tumor cells (H&E staining; original magnification,
x 480). (C) The tumor cells strongly express CD56. Image acquisition for
panels B and C was performed as described for Figure 1B. An HC Plan APO
40x/0.85 objective lens was used.
Laboratory examinations :
- histopathology : these lymphomas show nonepidermotropic, monotonous infiltrates of medium-sized cells with nuclei with a lacy chromatin,large cytoplasm-containing vacuoles or microvacuoles beside the plasma membrane, cytoplasmic expansions resembling pseudopodia, and absent or indistinct nucleoli resembling lymphoblasts or myeloblastsref1, ref2, ref3, ref4 (Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds). World Health Organization Classification of Tumors: Pathology and Genetics of Tumours of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC Press;2001). The cells have sparse cytoplasm. Mitotic figures are frequent. Inflammatory cells are absent. There is generally no necrosis or angioinvasion.
- immunophenotype : since lymphoblastic and myeloblastic neoplasms can also be positive for CD56, stains for CD3 and myeloperoxidase should always be performed in order to exclude these entities (Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds). World Health Organization Classification of Tumors: Pathology and Genetics of Tumours of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC Press;2001). The cells express CD123 and TCL1, both of which support a relationship to plasmacytoid dendritic cellsref1, ref2, ref3. From this new entity of leukemia, malignancies expressing myeloid markers were initially excludedref based on the assumption that these markers were not expressed by circulating normal pDCsref1, ref2, ref3, ref4, ref5 . Anyway a subsequent work found CD33 expression from 7 out of 8 patients tested as well as by normal circulating pDCs from 6 healthy donorsref. CD2-/+cyCD3-3-4+7+/-8-10-11a+11b-13-14-16-18+19-cyCD22-24-33+ref34-36+38+40+45+45RA+52-56+57-61-64-65-68+cyCD79a-84+91+95+117-/+123+133-184-w197+HLA-DR+MPO-TdT-BDCA-2+refBDCA-4+refgranzyme B+Ig-TcR-refIFN-a+cytotoxic proteins-refCXCR3+CXCR4+CCR6+CCR7+ref. Importantly, they become fully competent antigen-presenting cells (APC) after a short maturation induced by IL-3 + CD40L or virus, exhibiting a characteristic APC phenotype (high expression of CD83 and of the costimulatory molecules CD40, CD80, CD86). Whereas IL-3 + CD40L-activated LPDC prime naive CD4+ T cells towards a Th2 pathway (IL-4-secreting T cells), virus-activated LPDC drive a Th1 profile (IFN-g-secreting T cells). Moreover, LPDC are able to capture, process and present exogenous antigens, leading to the activation of both CD4+ and CD8+ T cell clones in an antigen-specific mannerref. IL-3- or virus-induced activation of LPDC leads to downregulation of CXCR3 and CXCR4, and upregulation of CCR7, associated with the loss of response to CXCL12, and the acquisition of sensitivity to CCL19ref
- cytogeneticsref1, ref2, ref3, ref4 : TcR genes are in germline configuration. Clonal, mostly complex chromosome aberrations were found in 14 patients (66%). Six major recurrent chromosomal targets were defined. These were 5q, 12p, 13q, 6q, 15q, and 9, which were involved in 72% (5q), 64% (12p and 13q), 50% (6q), 43% (15q), and 28% (monosomy 9) of cases, respectively. Cytogenetic features can be summarized as follows: (1) gross genomic imbalances (mostly losses) predominate, (2) no single anomaly can be considered as specific, whereas their combination/accumulation is, and (3) both lymphoid and myeloid lineage-associated rearrangements are observed in unusual combinations in the same cellref
-
tumor cells are negative for HHV-4 / EBV.
Therapy : recent studies suggest that patients can best be treated with regimens used in acute leukemiasref. Complete remission (CR) is frequently obtained (around 80%) with polychemotherapy. However, median time to relapse, mainly in the bone marrow, skin, or central nervous system, is about 9 (range 3–18) months and median survival is only 13 monthsref. Age > 60 years is a poor prognostic factor. Long term survival has only been reported following allogeneic HSCT
ref1,
ref2.
A case of CD4+ CD56+ lymphoma with prolonged survival
after an autologous PBSCT
has been reported. A 71-year-old male presented in the fall of 2001 with
facial erythema that progressed to several purple cutaneous nodules also
involving his trunk. Skin biopsy done in June 2002 confirmed the diagnosis
of CD4+CD56+ lymphoma of the skin. Staging studies
including CT scan of the chest, abdomen and pelvis, and bone marrow aspiration
and biopsy were negative. The patient received chemotherapy with CHOPE
(cyclophosphamide 750 mg/m2, adriamycin 50 mg/m2,
vincristine 1.4 mg/m2, prednisone 100 mg x 5 days, etoposide
120 mg/m2) for 6 cycles starting June 2002, and achieved a CR
with disappearance of all skin lesions. CT scan of the chest pretransplant
revealed a single 2 cm paratracheal lymph node that was also PET positive.
Stem cells were collected using cytoxan 4 gms/m2 followed by
10 mcg/kg/day of G-CSF. The patient underwent autologous stem cell transplantation
in February 2003 using BEAM (carmustine 300mg/m2 day –6, etopside
200mg/m2 days –5 to –2, cytarabine 400 mg/m2 days
–5 to –2, melphalan 140 mg/m2 day -1) as a preparative regimen.
Neutrophil engraftment occurred on day 10 and platelets engrafted on day
14 post SCT. The paratracheal lymph node was still visible on the PET scan
6 months post SCT. However, restaging studies at one year and beyond have
all been negative for disease reoccurrence including a CT chest that revealed
a calcified paratracheal lymph node that was negative on PET scan. The
patient continues to be in complete remission 37 months from diagnosis
and 30 months post SCT. The aggressive nature of CD4+CD56+
lymphoma is evident by its 9-month median time to relapse and short survival.
Therefore, aggressive treatment protocols incorporating stem cell transplant
should be utilized in their management and should not be limited to only
younger patients. As illustrated by our patient, the use of autologous
stem cell transplant in the elderly can be done safely with encouraging
resultsref
