© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
J Cutan Pathol 2014: 41: 73–77 doi: 10.1111/cup.12290 John Wiley & Sons. Printed in Singapore
Journal of Cutaneous Pathology
Cover Quizlet S Kindem, V Traves, C Requena, R Alcal´a, B Llombart, C Serra-Guill´en, E Nagore, C Guill´en and O Sanmartin Figures 1 and 2 are depicted on the journal cover.
Figure 3.
Figure 4. a
Figure 5. (CD 20)
b
Figure 6. a(CD 43), b(CD 5)
Your diagnosis? Discussion follows on page 74
73
Cover Quizlet
Bilateral cauliflower ear as the presenting sign of B-cell chronic lymphocytic leukemia S Kindem1 , V Traves2 , C Requena1 , R Alcal´a1 , B Llombart1 , C Serra-Guill´en1 , E Nagore1 , C Guill´en1 and O Sanmartin1 1
Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain 2 Department of Pathology, Instituto Valenciano de Oncologia, Valencia, Spain
Sabrina Kindem, C/Profesor Beltr´an Baguena, 4, 46009 Valencia, Spain. email: [email protected]. Phone number: 0034–961114015
Keywords: dermatopathology, chronic lymphocytic leukemia, leukemia cutis, cauliflower ear Accepted for publication December 8, 2013
B-cell chronic lymphocytic leukemia (B-CLL) represents the most common adult leukemia in Europe and North America.1 It is usually diagnosed by the finding of lymphocytosis, lymphadenopathy, or nonspecific manifestations related to an impaired immune system. Cutaneous lesions in patients with B-CLL are common but they usually occur late in the course of disease and typically present as erythematous papules, plaques or tumors(2) . The development of a leukemic skin infiltrate (leukemia cutis) constitutes a rare presenting sign of BCLL, and in such cases, histopathologic findings and immunohistochemical examination are key to a correct diagnosis. Typical findings include a lymphocytic infiltrate composed of small Blymphocytes in the dermis that are predominantly CD20-positive, with co-expression of CD23 and aberrant expression of CD5. We present a striking case of B-CLL with cutaneous involvement of both ears as the presenting feature. Isolated reports of this particular presentation suggest that bilateral cauliflower ear may represent an infrequent, albeit characteristic, presenting form of B-CLL. A 44-year-old man presented with a 4-year history of asymptomatic nodules on both ears. He was apparently healthy and had no history of cutaneous disease. The nodules were erythematous, coalescent lesions with a rosary-bead appearance; they were firm to the touch and covering the left and right helix and earlobe (Fig. 1 ).
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Fig. 1. Erythematous nodules cover the helices and lobes of the right and left ears.
Complete blood count with differential showed lymphocytosis (15,420/μl) with 6,163 B-lymphocytes/μl. Incisional cutaneous biopsy revealed a nodular infiltrate composed of small, round monomorphic lymphocytes with hyperchromatic nuclei and scant cytoplasm occupying the entire dermis; there was no epidermal involvement or evidence of epidermotropism (Fig. 3,4,5). The infiltrate expressed CD20, CD23, CD43 and CD5 and had a Ki-67 proliferation index of 25% (Figure 6). The infiltrate was negative for CD10 and cyclin D1, and a molecular genetics study showed a monoclonal rearrangement of the JH gene. A diagnosis of B-CLL was confirmed by
Cover Quizlet Table 1. Differential diagnosis of cauliflower ears Disease *
Trauma/hematoma
Perniosis
Lupus pernio (sarcoidosis)
Multicentric reticulohistiocytosis
Lupus vulgaris (tuberculosis)
Primary lymphoma
Lymphocytoma cutis
Auricular pseudocyst
Associated symptoms
Clinical characteristics
Histopathologic findings
Ear pain, deafness; usually no associated symptoms in other areas (dependent on type of trauma) Cutaneous lesions at cold temperatures
Billateral disfigurement to the ear, multiple nodules, usually normal skin color
Often associated with involvement of the upper respiratory tract and lungs Joint pain and fever
Violaceous nodules, particularly involving the nose, cheeks and ears
Hematoma between cartilage and perichondrium, fibrosis, abnormal fibrous cartilage formation Superficial and deep infiltrate, lymphocytic vasculitis, subepidermal edema and a peri-eccrine lymphocytic infiltrate, with or without interface change Sarcoidal granulomas
Respiratory symptoms or symptoms associated with areas affected by cutaneous tuberculosis Usually T-cell lymphoma; symptoms associated with other affected areas can be present. May be association with Borrelia burgdorferi infection; usually no other associated symptoms Auricular pain with no other associated symptoms
Relapsing polychondritis
Weight loss, joint pain and airway involvement; diverse other clinical manifestations
Rosai-Dorfman disease
Cervical lymphadenopathy, fever
Hansen disease (leprosy)
Neuropathic symptoms or symptoms associated with affected areas affected Often none
Cutaneous leishmaniasis
Blue-erythematous symmetric nodules
Multiple brown-yellow papules and nodules. The interphalangeal joints of the hands are usually affected. Multiple erythematous papules forming a plaque, which on diascopy shows small ‘apple jelly’ nodules Erythematous nodules with or without symmetric distribution
Circumscribed non-encapsulated dermal infiltrate and multinucleate histiocytes with an eosinophilic, finely granular ground-glass cytoplasm. Tuberculoid granulomas with a variable mantle of lymphocytes in the upper and middle dermis
Reddish purple nodule or tumor involving the earlobe, nipple or scrotum
Lymphoid follicles involving dermis and superficial subcutaneous tissue
Solitary/unilateral soft nodular lesion with ormal skin color
Intracartilaginous space with eosinophilic degeneration of cartilage and perichondrial fibrosis Cartilaginous fibrosis with focal destruction and a lymphoplasmacellular infiltrate
Bilateral redness and swelling, sparing the lobes; red eyes, saddle nose deformity, aphthous ulcers and purpura may also be seen Loss of the normal ear contours in both pinnae
Poorly defined nodules and plaques in both pinnae including lobes; facial deformity Unilateral erythematous nodules-plaques in the pinna; may ulcerate
Dermal infiltrate with atypical lymphocytes, depending on the type of lymphoma
Infiltrate of foamy histiocytes with prominent emperipolesis and an associated lymphoplasmacytic infiltrate Collections of histiocytes containing enormous numbers of acid-fast bacilli Epithelioid granulomas within the superficial and/or deep dermis.; observation of amastigote forms within monocytes or in extracellular spaces
*The most common diagnosis. Different causes in which the ear is repeatedly traumatized include some sports (wrestling, boxing, football), opium addiction or drug abuse (due to sleeping on hard surfaces), and rare cases of child abuse.
75
Cover Quizlet
Fig. 2. Hematoxylin and eosin staining demonstrates a nodular dense infiltrate with no epidermal changes.
bone marrow examination, which revealed small atypical lymphocytes replacing 85% of the cellular component of the marrow. Leukemia cutis constitutes a rare presenting sign of B-CLL. The lesions typically involve the face and neck, with a tendency to occur at sites of previous injury or infection, such as herpes simplex or herpes zoster scars or the site of prior Borrelia burgdorferi infection. Our patient had cauliflower-like lesions on both earlobes as the presenting sign of B-CLL. This peculiar and easily recognizable pattern was recently reported in a very similar case(3) . Earlobe infiltration may appear as the first sign of several systemic and cutaneous disorders. Table 1 summarizes the features of different entities in which cauliflower ears may be observed (4 – 9) . In B-CLL, cutaneous manifestations generally occur late in the course of disease and are variably seen (in 3-45%) in patients(10) . A specific cutaneous infiltrate of B-CLL can appear as erythematous papules, plaques, nodules or large tumors. Ulceration is uncommon. Localized lesions are found on the head and neck, trunk, or extremities(2) . The head and neck may be frequently affected because they are sites of herpes simplex and Borrelia burgdorferi infection, and a cutaneous infiltrate may affect the ears and nose in many types of lymphoproliferative disorders(11) . Cutaneous manifestations are rarely the presenting sign of B-CLL, and only a few cases have been reported in the medical literature. Three
histopathologic patterns have been described: i) a patchy dense perivascular and periadnexal lymphoid infiltrate (the most common pattern), ii) a nodulardiffuse lymphoid infiltrate in the middle and deep dermis (as in our case), and iii) a band-like pattern characterized by a dense infiltrate arranged in a band in the superficial and middle dermis(2,12) . The infiltrate consists predominantly of B-cells that are immunohistochemically positive for CD19 and CD20 and have aberrant expression of the T-cell marker CD5. The lack of cyclin D1 expression may be useful in distinguishing B-CLL from mantle cell lymphoma. Mantle cell lymphoma typically expresses both CD5 and cyclin D1(13) . The occurrence of leukemia cutis in B-CLL has been considered a poor prognostic sign(1) . However, some authors have suggested that patients with B-CLL and cutaneous involvement may have prolonged survival(14) . In a study of the histopathologic findings of cutaneous B-CLL, Kaddu et al(12) observed two microscopic patterns that had a significant prognostic impact during follow-up. The first pattern, characterized by a B-cell infiltrate in the dermis without reactive lymphocytes or epidermal changes, was associated with long survival (2-year survival rate of 97%). The second and less common pattern, characterized by medium and large B-cells with an admixture of reactive cells and epidermal changes, was associated with a 2-year survival rate of just 49%. The authors suggested that the histopathologic features of a specific B-CLL skin infiltrate may help to identify prognostically different subgroups of patients. In conclusion, we posit that bilateral cauliflower ear may be a characteristic, although infrequent, presenting form of B-CLL. Figs 3–4. The infiltrate is composed of small to medium-sized lymphocytes without admixed reactive cells. Fig 5. Diffuse expression of CD20 was noted. Figs 6a-6b. There was diffuse aberrant expression of CD43 and CD5. The Ki-67 cell proliferation index was 25% (not shown).
References: 1. Redaelli A, Laskin BL, Stephens JM, Botteman MF, Pashos CL. The clinical and epidemiological burden of chronic lymphocytic leukaemia. Eur J Cancer Care 2004; 13: 279. 2. Cerroni L, Zenahlik P, H¨ofler G, Kaddu S, Smolle J, Kerl H. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: a
76
clinicopathologic and prognostic study of 42 patients. Am J Surg Pathol 1996; 20: 1000. 3. Kim PS, Sheth PB. Asymptomatic cauliflower ears in a 73-year-old man. Diagnosis: Leukemia cutis in the setting of indolent Bcell chronic lymphocytic leukemia (B-CLL). Arch Dermatol 2011; 147: 1443.
4. Giffin CS. Wrestler’s ear: pathophysiology and treatment. Ann Plast Surg 1992; 28: 131. 5. Muthusamy E. Opium addiction and cauliflower ears: a case report. Singapore Med J 1991; 32: 90. 6. Cuesta L, Betlloch I, Ba˜nuls J, Toledo F. «Cauliflower ear» in a teenager: a possible
Cover Quizlet sign of child abuse. Pediatr Dermatol. 2012; 29: 226. 7. Oo KKK, Pang YT, Thamboo TP. Bilateral cauliflower ear deformity: an unusual presentation of cutaneous Rosai-Dorfman disease. Plast Reconstr Surg 2004; 113: 967. 8. Shuto J, Ueyama T, Suzuki M, Mogi G. Primary lymphoma of bilateral external auditory canals. Am J Otolaryngol 2002; 23: 49. ¨ C 9. Tarkan O, ¸ etık F, Uzun S. Auricular cutaneous leishmaniasis mimicking neoplastic disease. J Laryngol Otol 2012; 126: 821.
10. Ali L, Cheney R, Merzianu M. Subclinical chronic lymphocytic leukemia with atypical cutaneous presentation. J Cutan Pathol 2011; 38: 236. 11. Cervig´on I, Palomo A, Torres-Iglesias LM, Solano F, Zapata AM. [Specific palatal infiltration in B-cell chronic lymphocytic leukemia]. Actas Dermosifiliogr.2011;102():305–7. 12. Kaddu S, Smolle J, Cerroni L, Kerl H. Prognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic leukemia. J Cutan Pathol 1996; 23: 487.
13. Matutes E, Owusu-Ankomah K, Morilla R, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 1994; 8: 1640. 14. Colburn DE, Welch M-A, Giles FJ. Skin infiltration with chronic lymphocytic leukemia is consistent with a good prognosis. Hematology 2002; 7: 187.
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J Cutan Pathol 2014: 41: 73–77 doi: 10.1111/cup.12290 John Wiley & Sons. Printed in Singapore
Journal of Cutaneous Pathology
Cover Quizlet S Kindem, V Traves, C Requena, R Alcal´a, B Llombart, C Serra-Guill´en, E Nagore, C Guill´en and O Sanmartin Figures 1 and 2 are depicted on the journal cover.
Figure 3.
Figure 4. a
Figure 5. (CD 20)
b
Figure 6. a(CD 43), b(CD 5)
Your diagnosis? Discussion follows on page 74
73
Cover Quizlet
Bilateral cauliflower ear as the presenting sign of B-cell chronic lymphocytic leukemia S Kindem1 , V Traves2 , C Requena1 , R Alcal´a1 , B Llombart1 , C Serra-Guill´en1 , E Nagore1 , C Guill´en1 and O Sanmartin1 1
Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain 2 Department of Pathology, Instituto Valenciano de Oncologia, Valencia, Spain
Sabrina Kindem, C/Profesor Beltr´an Baguena, 4, 46009 Valencia, Spain. email: [email protected]. Phone number: 0034–961114015
Keywords: dermatopathology, chronic lymphocytic leukemia, leukemia cutis, cauliflower ear Accepted for publication December 8, 2013
B-cell chronic lymphocytic leukemia (B-CLL) represents the most common adult leukemia in Europe and North America.1 It is usually diagnosed by the finding of lymphocytosis, lymphadenopathy, or nonspecific manifestations related to an impaired immune system. Cutaneous lesions in patients with B-CLL are common but they usually occur late in the course of disease and typically present as erythematous papules, plaques or tumors(2) . The development of a leukemic skin infiltrate (leukemia cutis) constitutes a rare presenting sign of BCLL, and in such cases, histopathologic findings and immunohistochemical examination are key to a correct diagnosis. Typical findings include a lymphocytic infiltrate composed of small Blymphocytes in the dermis that are predominantly CD20-positive, with co-expression of CD23 and aberrant expression of CD5. We present a striking case of B-CLL with cutaneous involvement of both ears as the presenting feature. Isolated reports of this particular presentation suggest that bilateral cauliflower ear may represent an infrequent, albeit characteristic, presenting form of B-CLL. A 44-year-old man presented with a 4-year history of asymptomatic nodules on both ears. He was apparently healthy and had no history of cutaneous disease. The nodules were erythematous, coalescent lesions with a rosary-bead appearance; they were firm to the touch and covering the left and right helix and earlobe (Fig. 1 ).
74
Fig. 1. Erythematous nodules cover the helices and lobes of the right and left ears.
Complete blood count with differential showed lymphocytosis (15,420/μl) with 6,163 B-lymphocytes/μl. Incisional cutaneous biopsy revealed a nodular infiltrate composed of small, round monomorphic lymphocytes with hyperchromatic nuclei and scant cytoplasm occupying the entire dermis; there was no epidermal involvement or evidence of epidermotropism (Fig. 3,4,5). The infiltrate expressed CD20, CD23, CD43 and CD5 and had a Ki-67 proliferation index of 25% (Figure 6). The infiltrate was negative for CD10 and cyclin D1, and a molecular genetics study showed a monoclonal rearrangement of the JH gene. A diagnosis of B-CLL was confirmed by
Cover Quizlet Table 1. Differential diagnosis of cauliflower ears Disease *
Trauma/hematoma
Perniosis
Lupus pernio (sarcoidosis)
Multicentric reticulohistiocytosis
Lupus vulgaris (tuberculosis)
Primary lymphoma
Lymphocytoma cutis
Auricular pseudocyst
Associated symptoms
Clinical characteristics
Histopathologic findings
Ear pain, deafness; usually no associated symptoms in other areas (dependent on type of trauma) Cutaneous lesions at cold temperatures
Billateral disfigurement to the ear, multiple nodules, usually normal skin color
Often associated with involvement of the upper respiratory tract and lungs Joint pain and fever
Violaceous nodules, particularly involving the nose, cheeks and ears
Hematoma between cartilage and perichondrium, fibrosis, abnormal fibrous cartilage formation Superficial and deep infiltrate, lymphocytic vasculitis, subepidermal edema and a peri-eccrine lymphocytic infiltrate, with or without interface change Sarcoidal granulomas
Respiratory symptoms or symptoms associated with areas affected by cutaneous tuberculosis Usually T-cell lymphoma; symptoms associated with other affected areas can be present. May be association with Borrelia burgdorferi infection; usually no other associated symptoms Auricular pain with no other associated symptoms
Relapsing polychondritis
Weight loss, joint pain and airway involvement; diverse other clinical manifestations
Rosai-Dorfman disease
Cervical lymphadenopathy, fever
Hansen disease (leprosy)
Neuropathic symptoms or symptoms associated with affected areas affected Often none
Cutaneous leishmaniasis
Blue-erythematous symmetric nodules
Multiple brown-yellow papules and nodules. The interphalangeal joints of the hands are usually affected. Multiple erythematous papules forming a plaque, which on diascopy shows small ‘apple jelly’ nodules Erythematous nodules with or without symmetric distribution
Circumscribed non-encapsulated dermal infiltrate and multinucleate histiocytes with an eosinophilic, finely granular ground-glass cytoplasm. Tuberculoid granulomas with a variable mantle of lymphocytes in the upper and middle dermis
Reddish purple nodule or tumor involving the earlobe, nipple or scrotum
Lymphoid follicles involving dermis and superficial subcutaneous tissue
Solitary/unilateral soft nodular lesion with ormal skin color
Intracartilaginous space with eosinophilic degeneration of cartilage and perichondrial fibrosis Cartilaginous fibrosis with focal destruction and a lymphoplasmacellular infiltrate
Bilateral redness and swelling, sparing the lobes; red eyes, saddle nose deformity, aphthous ulcers and purpura may also be seen Loss of the normal ear contours in both pinnae
Poorly defined nodules and plaques in both pinnae including lobes; facial deformity Unilateral erythematous nodules-plaques in the pinna; may ulcerate
Dermal infiltrate with atypical lymphocytes, depending on the type of lymphoma
Infiltrate of foamy histiocytes with prominent emperipolesis and an associated lymphoplasmacytic infiltrate Collections of histiocytes containing enormous numbers of acid-fast bacilli Epithelioid granulomas within the superficial and/or deep dermis.; observation of amastigote forms within monocytes or in extracellular spaces
*The most common diagnosis. Different causes in which the ear is repeatedly traumatized include some sports (wrestling, boxing, football), opium addiction or drug abuse (due to sleeping on hard surfaces), and rare cases of child abuse.
75
Cover Quizlet
Fig. 2. Hematoxylin and eosin staining demonstrates a nodular dense infiltrate with no epidermal changes.
bone marrow examination, which revealed small atypical lymphocytes replacing 85% of the cellular component of the marrow. Leukemia cutis constitutes a rare presenting sign of B-CLL. The lesions typically involve the face and neck, with a tendency to occur at sites of previous injury or infection, such as herpes simplex or herpes zoster scars or the site of prior Borrelia burgdorferi infection. Our patient had cauliflower-like lesions on both earlobes as the presenting sign of B-CLL. This peculiar and easily recognizable pattern was recently reported in a very similar case(3) . Earlobe infiltration may appear as the first sign of several systemic and cutaneous disorders. Table 1 summarizes the features of different entities in which cauliflower ears may be observed (4 – 9) . In B-CLL, cutaneous manifestations generally occur late in the course of disease and are variably seen (in 3-45%) in patients(10) . A specific cutaneous infiltrate of B-CLL can appear as erythematous papules, plaques, nodules or large tumors. Ulceration is uncommon. Localized lesions are found on the head and neck, trunk, or extremities(2) . The head and neck may be frequently affected because they are sites of herpes simplex and Borrelia burgdorferi infection, and a cutaneous infiltrate may affect the ears and nose in many types of lymphoproliferative disorders(11) . Cutaneous manifestations are rarely the presenting sign of B-CLL, and only a few cases have been reported in the medical literature. Three
histopathologic patterns have been described: i) a patchy dense perivascular and periadnexal lymphoid infiltrate (the most common pattern), ii) a nodulardiffuse lymphoid infiltrate in the middle and deep dermis (as in our case), and iii) a band-like pattern characterized by a dense infiltrate arranged in a band in the superficial and middle dermis(2,12) . The infiltrate consists predominantly of B-cells that are immunohistochemically positive for CD19 and CD20 and have aberrant expression of the T-cell marker CD5. The lack of cyclin D1 expression may be useful in distinguishing B-CLL from mantle cell lymphoma. Mantle cell lymphoma typically expresses both CD5 and cyclin D1(13) . The occurrence of leukemia cutis in B-CLL has been considered a poor prognostic sign(1) . However, some authors have suggested that patients with B-CLL and cutaneous involvement may have prolonged survival(14) . In a study of the histopathologic findings of cutaneous B-CLL, Kaddu et al(12) observed two microscopic patterns that had a significant prognostic impact during follow-up. The first pattern, characterized by a B-cell infiltrate in the dermis without reactive lymphocytes or epidermal changes, was associated with long survival (2-year survival rate of 97%). The second and less common pattern, characterized by medium and large B-cells with an admixture of reactive cells and epidermal changes, was associated with a 2-year survival rate of just 49%. The authors suggested that the histopathologic features of a specific B-CLL skin infiltrate may help to identify prognostically different subgroups of patients. In conclusion, we posit that bilateral cauliflower ear may be a characteristic, although infrequent, presenting form of B-CLL. Figs 3–4. The infiltrate is composed of small to medium-sized lymphocytes without admixed reactive cells. Fig 5. Diffuse expression of CD20 was noted. Figs 6a-6b. There was diffuse aberrant expression of CD43 and CD5. The Ki-67 cell proliferation index was 25% (not shown).
References: 1. Redaelli A, Laskin BL, Stephens JM, Botteman MF, Pashos CL. The clinical and epidemiological burden of chronic lymphocytic leukaemia. Eur J Cancer Care 2004; 13: 279. 2. Cerroni L, Zenahlik P, H¨ofler G, Kaddu S, Smolle J, Kerl H. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: a
76
clinicopathologic and prognostic study of 42 patients. Am J Surg Pathol 1996; 20: 1000. 3. Kim PS, Sheth PB. Asymptomatic cauliflower ears in a 73-year-old man. Diagnosis: Leukemia cutis in the setting of indolent Bcell chronic lymphocytic leukemia (B-CLL). Arch Dermatol 2011; 147: 1443.
4. Giffin CS. Wrestler’s ear: pathophysiology and treatment. Ann Plast Surg 1992; 28: 131. 5. Muthusamy E. Opium addiction and cauliflower ears: a case report. Singapore Med J 1991; 32: 90. 6. Cuesta L, Betlloch I, Ba˜nuls J, Toledo F. «Cauliflower ear» in a teenager: a possible
Cover Quizlet sign of child abuse. Pediatr Dermatol. 2012; 29: 226. 7. Oo KKK, Pang YT, Thamboo TP. Bilateral cauliflower ear deformity: an unusual presentation of cutaneous Rosai-Dorfman disease. Plast Reconstr Surg 2004; 113: 967. 8. Shuto J, Ueyama T, Suzuki M, Mogi G. Primary lymphoma of bilateral external auditory canals. Am J Otolaryngol 2002; 23: 49. ¨ C 9. Tarkan O, ¸ etık F, Uzun S. Auricular cutaneous leishmaniasis mimicking neoplastic disease. J Laryngol Otol 2012; 126: 821.
10. Ali L, Cheney R, Merzianu M. Subclinical chronic lymphocytic leukemia with atypical cutaneous presentation. J Cutan Pathol 2011; 38: 236. 11. Cervig´on I, Palomo A, Torres-Iglesias LM, Solano F, Zapata AM. [Specific palatal infiltration in B-cell chronic lymphocytic leukemia]. Actas Dermosifiliogr.2011;102():305–7. 12. Kaddu S, Smolle J, Cerroni L, Kerl H. Prognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic leukemia. J Cutan Pathol 1996; 23: 487.
13. Matutes E, Owusu-Ankomah K, Morilla R, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 1994; 8: 1640. 14. Colburn DE, Welch M-A, Giles FJ. Skin infiltration with chronic lymphocytic leukemia is consistent with a good prognosis. Hematology 2002; 7: 187.
77
