Identificación de la competencia

Fig. 13.1 Cutaneous B-lymphoblastic lymphoma. Large tumour on the face of an 18-month-old child.

Fig. 13.2 Cutaneous B-lymphoblastic lymphoma. Small erythematous papule on the chest as first sign of recurre nce of acute lymphoblastic leukaemia in a 28-year-old man (histopathological and

immunophenotypical features are depicted in Fig. 13.6).

Fig. 13.3 Cutaneous B-lymphoblastic lymphoma. B lymphoblasts with round nuclei and finely dispersed chromatin.

Fig. 13.4 Cutaneous B-lymphoblastic lymphoma. Monomorphous proliferation of medium-sized cells. Note ‘starry sky’ pattern.

Fig. 13.5 Cutaneous B-lymphoblastic lymphoma. Note ‘mosaic stone’- like arrangement of neoplastic cells.

Fig. 13.6 Cutaneous B-lymphoblastic lymphoma (same case as Fig. 13.2). (a) Dense perivascular infiltrates in the super ficial and mid- dermis. (b) Monomorphous medium-sized cells predominate. Most neoplastic cells show nuclear positivity for (c) TdT and (d) CD34.

Molecular genetics

Molecular genetics usually shows a monoclonal rearrange- ment of the J_H gene and a polyclonal pattern of the T-cell receptor (TCR) gene. In rare instances, a concomitant mono- clonal rearrangement of the TCR gene can be observed, giving rise to potential pitfalls in the molecular diagnosis of  the tumour.

The differential diagnosis of B-lymphoblastic lymphoma includes several entities that may show similar morpholog- ical features. Mantle cell lymphoma contains cells with more cleaved or irregularly shaped nuclei and a characteristic immunophenotype (CD5+_{, cyclin-D1}+_{, CD10}–_{, TdT}–_{) (see}

Chapter 15). Myelomonocytic leukaemia shows a prolifera-

(a) (b)

B-Lymphoblastic Lymphoma 119

tion of immature myeloid cells with figurate or ‘Indian-line’ patterns that stain positive for myeloid markers (naphthol- ASD-chloracetate-esterase, myeloperoxidase) and do not reveal a monoclonal rearrangement of the J_H gene (see Chapter 18). Blastic NK-cell lymphoma is characterized by a strong positivity for CD4 and CD56 in addition to a variable positivity for TdT, as well as by a lack of rearrangement of the J_Hgene (see Chapter 16). The differential diagnosis may  also include cutaneous Merkel cell tumours and metastatic neuroendocrine carcinomas, which are characterized by the coexpression of cytokeratin filaments, neurofilament pro- teins and various other markers (chromogranin A) in addi- tion to the lack of expression of lymphoid markers and presence of J_Hgene rearrangement.

These patients should be managed in a haematological set- ting. The treatment of choice is systemic chemotherapy, often with bone marrow transplantation. Patients with local- ized skin disease appear to have a relatively good prognosis, but treatment strategies should be the same as those for systemic variants of the disease.

1 Brunning RD, Borowitz M, Matutes E et al . Precursor B lymphoblas- tic leukaemia/lymphoblastic lymphoma (precursor B-cell acute lymphoblastic leukaemia). In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of  Tumours: Tumours of Haematopoietic and Lymphoid Tissues.Lyon: IARC Press, 2001: 111–4.

2 Sander CA, Medeiros LJ, Abruzzo LV, Horak ID, Jaffe ES. Lym- phoblastic lymphoma presenting in cutaneous sites: a clinicopatho- logic analysis of six cases. J Am Acad Dermatol 1991;25_{: 1023–31.}

3 Chimenti S, Fink-Puches R, Peris K et al . Cutaneous involvement in lymphoblastic lymphoma. J Cutan Pathol 1999;26_{: 379–85.}

4 Schmitt IM, Manente L, Di Matteo A et al . Lymphoblastic lym- phoma of the pre-B phenotype with cutaneous presentation. Dermatology 1997;195_{: 289–92.}

5 Trupiano JK, Bringelsen K, Hsi E. Primary cutaneous lymphoblastic lymphoma presenting in an 8-week-old infant. J Cutan Pathol 2002;

29_{: 107–12.}

6 Grümayer ER, Ladenstein RL, Slavc I et al . B-cell differentiation pattern of cutaneous lymphomas in infancy and childhood. Cancer  1988;61_{: 303– 8.}

7 Kamps WA, Poppema S. Pre-B-cell non-Hodgkin’s lymphoma in childhood. Am J Clin Pathol 1988;90_{: 103–7.}

8 Knowles DM. Lymphoblastic lymphoma. In: Knowles DM, ed.  Neoplastic Hematopathology . Philadelphia: Lippincott, 2001: 915–

51.

9 Kahwash SB, Qualman SJ. Cutaneous lymphoblastic lymphoma in children: report of six cases with precursor B-cell lineage. Pediatr  Dev Pathol 2002;5_{: 45–53.}

10 Momoi A, Toba K, Kawai K et al . Cutaneous lymphoblastic lym- phoma of putative plasmacytoid dendritic cell-precursor origin: two cases. Leuk Res 2002;26_{: 693– 8.}

11 Maitra A, McKenna RW, Weinberg AG, Schneider NR, Kroft SH. Precursor B-cell lymphoblastic lymphoma: a study of nine cases lacking blood and bone marrow involvement and review of the liter- ature. Am J Clin Pathol 2001;115_{: 868–75.}

12 Lin P, Jones D, Dorfman DM, Medeiros LJ. Precursor B-cell lym- phoblastic lymphoma: a predominantly extranodal tumor with low  propensity for leukemic involvement.  Am J Surg Pathol 2000;24_:

1480–90.

13 Yen A, Sanchez R, Oblender M, Raimer S. Leukemia cutis: Darier’s sign in a neonate with acute lymphoblastic leukemia.  J Am Acad  Dermatol 1996;34_{: 375– 8.}

References

Treatment and prognosis

RÉSUMÉ

Clinical Childen, young adults. Solitary tumours. Preferential location: head and neck.

Morphology Nodular or diffuse infiltrates characterized by monomorphous proliferations of lymphoblasts. Immunology CD20, 79a + CD10 + CD34 + /– TdT +

Genetics Monoclonal rearrangement of the J_Hgene detected in the majority of cases.

Treatment Systemic chemotherapy; bone marrow

guidelines transplantation.

Fig. 13.7 Cutaneous B-lymphoblastic lymphoma. Most neoplastic cells show positivity for CD10.

B-cell chronic lymphocytic leukaemia (B-CLL) represents the most frequent type of chronic lymphocytic leukaemia. Cutaneous lesions in patients affected by B-CLL are com- mon. In most instances they represent non-specific manifesta- tions related to the impaired immune competence of these patients or to the ingestion of drugs. In some cases, neoplastic B lymphocytes are found within the skin [1]. Such lesions are referred to as specific cutaneous manifestations of the disease or ‘leukaemia cutis’.

Clinically, patients present with localized or generalized ery- thematous papules, plaques or tumours [1–3]. Peculiar clin- ical presentations include the so-called ‘facies leonina’ and the onset of specific skin lesions at sites of previous herpes simplex or herpes zoster eruptions (Figs 14.1 & 14.2) [4]. These latter were often classified in the past as pseudolym- phoma [5,6], but are in fact specific cutaneous manifesta- tions of the disease [4,7]. It has been recently demonstrated that lesions arising at typical sites of Borrelia burgdorferi infection (nipple, scrotum, earlobe) represent specific mani- festations of B-CLL triggered by infection with B. burgdorferi (Fig. 14.3) [8]. Lesions arising on the nipple were well known in the past and were termed ‘leukaemia lymphatica mamil lae’ in old textbooks.

Histopathology

Histology may show either a patchy perivascular and p eriad- nexal pattern, or the presence of dense, monomorphous, dif- fuse or nodular infiltrates of lymphocytes (Fig. 14.4) [4]. The subcutaneous fat is involved as a rule. The tumour is com- posed predominantly of small lymphocytes without atypical features (Fig. 14.5). Small nodular areas with larger cells

Histopathology, immunophenotype

and molecular genetics

Clinical features

leukaemia

Fig. 14.1 Cutaneous B-cell chronic lymphocytic leukaemia (B-CLL). Nodules on the face conferring the aspect o f the so-called ‘facies leonina’.

showing features of prolymphocytes or paraimmunoblasts (so-called ‘proliferation centres’) can be observed occasion- ally [4]. In some cases, other cells such as eosinophils and epithelioid histiocytes can be found.

In patients with B-CLL, infiltrates of neoplastic lym- phocytes may be observed in biopsy specimens of different cutaneous conditions, representing specific manifestations of the disease at sites of skin inflammation caused by differ- ent aetiological factors [4,8,9]. A case of cutaneous ‘com- posite’ lymphoma with features of both mycosis fungoides and B-CLL has been observed [10], probably representing a further example of the phenomenon just described.

B-cell Chronic Lymphocytic Leukaemia 121

Immunophenotype and molecular genetics

Immunohistology reveals the presence of B lymphocytes characterized by an aberrant immunophenotype (CD20+_,

CD5+_{, CD43}+_{) and monoclonal expression of immunoglob-}

ulin light-chains (Fig. 14.6) [4]. CD5 may be negative in some cases. A variable population of reactive T lymphocytes is usually present. Molecular genetics shows in most cases a monoclonal rearrangement of the J_Hgene.

The prognosis seems not to be affected by skin involvement [4]. The treatment must be planned according to the haema- tological findings. Small solitary or clustered skin lesions may 

Treatment and prognosis

Fig. 14.2 Cutaneous B-CLL. Specific skin manifestations at the site of a previous herpes zoster eruption.

Fig. 14.3 Cutaneous B-CLL. Specific skin manifestation at t he site of aBorrelia burgdorferi infection (so-called ‘leukaemia lymphatica mamillae’).

Fig. 14.4 Cutaneous B-CLL. Dense lymphoid infiltrates within the dermis and subcutaneous fat.

Fig. 14.5 Cutaneous B-CLL. Monomorphous infiltrate of small lymphocytes.

be removed surgically or by carbon dioxide laser vaporiza- tion [2]. Larger lesions may be treated by radiotherapy. Positive responses to UVB therapy have been reported [11]. Rarely, skin manifestations may regress slowly without any  specific treatment [12].

Large cell transformation of B-CLL (Richter syndrome) has been reported occasionally in the skin [4,13,14]. Patients present clinically with solitary large cutaneous tumours. His- tology reveals features of a large B-cell lymphoma with many  centroblasts and immunoblasts. Immunohistology shows positivity for B-cell markers, often with an aberrant profile