letter to editor Simultaneous occurrence of a CD30 positive/ALK-negative high grade T-cell lymphoma and plasma cell myeloma: Report of a case Simultaneous occurrences of T-cell and B-cell neoplasms are rare, and etiological relationships between these two malignancies are poorly understood. We report the case of a 76-year-old man who presented with hypercalcemia, multiple skin nodular lesions, fatigue, episodic fever, and night sweats. PET/CT scan showed diffuse skin and subcutaneous fat plane active lesions, supra- and infra- diaphragmatic active lymph nodes, liver and spleen involvement, bone marrow infiltration, and nonspecific bilateral lung nodules. A skin biopsy showed a high grade CD30-positive/ALK-negative T-cell lymphoma. A bone marrow biopsy showed involvement by the same neoplastic cells. Additionally, a monoclonal lambda restricted plasma cell population (15% of marrow elements) was identified, which, in view of an IgA lambda spike in the serum, was consistent with plasma cell myeloma. To the best of our knowledge, this case is the first reported case of a plasma cell neoplasm associated with an aggressive CD30-positive ALK-negative systemic T-cell lymphoma with skin involvement. Reporting such cases is important as it adds to the pool of rare cases of concomitant T-cell neoplasms and plasma cell myelomas, and might help in determining an etiological relationship, if any, between these two hematological malignancies. Simultaneous occurrences of T-cell and B-cell lymphoproliferative disorders have rarely been
40
described.1 Of note, several cases of T-cell lymphomas, including primary cutaneous lymphomas in association with clonal plasma cell proliferations, have been reported with variable clinical presentation.1–3 However, the relationship between these two neoplasms remains poorly understood. A 76-year-old man with known chronic renal insufficiency presented with a one month history of multiple diffuse skin nodules. At presentation, he was found to have anemia (hemoglobin: 10.9 g/dL) and hypercalcemia (serum calcium: 11.1 mg/dL). Serum protein electrophoresis and immunofixation revealed an IgA lambda spike (9.6 g/L). On physical examination, the patient had multiple cutaneous skin-colored to erythematous papules and nodules, involving his bilateral lower and upper extremities and trunk (Figure 1A and B). A PET/CT scan showed multiple diffuse active lesions in the skin, subcutaneous tissue, lung, liver, spleen, and bone marrow, and multiple active lymph nodes. A skin biopsy showed a superficial and deep dermal infiltrate sparing the epidermis, consisting of medium to large-sized atypical cells with irregular nuclei, occasionally prominent nucleoli, variable chromatin pattern, and high mitotic activity (Figure 1C and D). No anaplastic-looking cells were seen. The atypical cells were positive for CD45, CD3, CD30 (strong and diffuse), CD43, and negative for ALK, CD4, CD5, CD7, CD8, CD10, CD20, CD34, CD56, TdT, PAX-5, myeloperoxidase, BCL-6, PD-1, and in situ hybridization for EBVencoded RNA (Figure 1E and F). Ki-67 proliferation index was around 90%. The bone marrow
biopsy showed involvement by similar atypical cells (Figure 1G and H), with marked (3+) increase in reticulin fibrosis (not shown). Furthermore, there was an increase in CD138-positive lambda light chain-restricted plasma cells (Figure 1H–J), accounting for around 15% of marrow elements. The overall findings were consistent with an aggressive CD30-positive T-cell neoplasm involving multiple organs with a concomitant IgA lambda-secreting plasma cell myeloma. Unfortunately, shortly after the diagnosis was made, the patient’s condition rapidly deteriorated, leading to his demise. According to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, the main differential diagnoses in this case include ALK-negative anaplastic large cell lymphoma (ALCL) and CD30-positive peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS).4 We followed the WHO conservative approach where ALK-negative ALCL should be diagnosed only in cases where the morphology and the immunophenotype are very similar to those of the ALK-positive cases.4 We believed that the overall clinical and histologic findings were more consistent with a PTCL, NOS than an ALCL or a primary cutaneous T-cell lymphoma. Interestingly, there was a concomitant plasma cell myeloma (PM) in the bone marrow. The relationship between T-cell neoplasms and PM is unclear, as various studies have described different possible mechanisms for tumorigenesis.2,3,5,6 Therefore, the chronological sequence of tumors could not be determined with certainty.
Hematol Oncol Stem Cell Ther 8(1)
First Quarter 2015
letter to editor
Figure 1. Right lower extremity (A) and left upper extremity (B) skin lesions. Superficial and deep infiltrate dermal infiltrate (H&E, 40·) (C), consisting of medium to largesized atypical cells with irregular nuclei, occasionally prominent nucleoli, variable chromatin pattern, and a high mitotic activity, sparing the epidermis (H&E, 400·) (D). Diffuse positivity for CD3 (E) and CD30 (F) in the atypical infiltrate, with no expression of CD5 or ALK (not shown). Hypercellular bone marrow diffusely involved by an atypical cell population (H&E, 40·) (G), morphologically similar to the infiltrate in the skin, admixed with clusters of plasma cells (H&E, 400·) (H). Increased plasma cells highlighted by CD138 (I) showing lambda light chain restriction (J), and negative for kappa light chains (not shown).
In summary, this case is of value because, to the best of our knowledge, it is the first reported case of a plasma cell neoplasm associated with an aggressive
Hematol Oncol Stem Cell Ther 8(1)
First Quarter 2015
CD30-positive PTCL, NOS. Reporting such cases is important as it adds to the pool of rare cases of concomitant T-cell neoplasms and plasma cell myelomas, and
might help in determining an etiological relationship, if any, between these two hematological malignancies.
41
letter to editor CONFLICT OF INTEREST/ SOURCES OF FUNDING
Center, Beirut, Lebanon * Corresponding author at:
The authors have no conflict of interest or sources of funding to disclose.
Department of Pathology and
Samer Nassif a,*, Nadim El-Majzoub a, Ossama Abbas b, Sally Temraz c, Zaher Chakhachiro a
Beirut, Lebanon. Tel.: +961 1 350
a
Department of Pathology and
Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon,
b
Laboratory Medicine, American University of Beirut Medical Center, P.O. Box 11-0236, Riad El Solh 110, 72020 000x5188; fax: +961 1 370 845. [email protected] ª 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/3.0/). DOI: http://dx.doi.org/10.1016/ j.hemonc.2014.11.004
Department of
Dermatology, American University of
REFERENCES
T-cell lymphoma in the same patient: is there a causal relation? J. Cutan. Pathol. 2011;38(3): 298–300. 2. Cartron G, Roingeard P, Benboubker L, Vaillant L, Tartas S, Delain M, et al.. Sezary syndrome in a patient with multiple myeloma: demonstration of a clonally distinct second malignancy. Eur. J. Haematol. 1999;63(5):354–7. 3. Gernone A, Frassanito MA, Pellegrino A, Vacca A, Dammacco F. Multiple myeloma and mycosis fungoides in the same patient: clinical, immunologic, and molecular studies. Ann. Hematol. 2002;81(6):326–31. 4. Mason DY, Harris NL, Delsol G, Stein H, Campo E, Kinney MC, et al.. Anaplastic large cell lymphoma, ALK-negative. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008. p. 317–9. 5. Prabhala RH, Neri P, Bae JE, Tassone P, Shammas MA, Allam CK, et al.. Dysfunctional T regulatory cells in multiple myeloma. Blood 2006;107(1):301–4. 6. Dunleavy K, Wilson WH, Jaffe ES. Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical implications. Curr. Opin. Hematol. 2007;14(4):348–53.
Beirut Medical Center, Beirut, Lebanon, c
Department of Internal Medicine,
American University of Beirut Medical
42
1. Tangour M, Chelly I, Haouet S, Zitouna M, Kchir N. Multiple myeloma and cutaneous anaplastic large
Hematol Oncol Stem Cell Ther 8(1)
First Quarter 2015
40
described.1 Of note, several cases of T-cell lymphomas, including primary cutaneous lymphomas in association with clonal plasma cell proliferations, have been reported with variable clinical presentation.1–3 However, the relationship between these two neoplasms remains poorly understood. A 76-year-old man with known chronic renal insufficiency presented with a one month history of multiple diffuse skin nodules. At presentation, he was found to have anemia (hemoglobin: 10.9 g/dL) and hypercalcemia (serum calcium: 11.1 mg/dL). Serum protein electrophoresis and immunofixation revealed an IgA lambda spike (9.6 g/L). On physical examination, the patient had multiple cutaneous skin-colored to erythematous papules and nodules, involving his bilateral lower and upper extremities and trunk (Figure 1A and B). A PET/CT scan showed multiple diffuse active lesions in the skin, subcutaneous tissue, lung, liver, spleen, and bone marrow, and multiple active lymph nodes. A skin biopsy showed a superficial and deep dermal infiltrate sparing the epidermis, consisting of medium to large-sized atypical cells with irregular nuclei, occasionally prominent nucleoli, variable chromatin pattern, and high mitotic activity (Figure 1C and D). No anaplastic-looking cells were seen. The atypical cells were positive for CD45, CD3, CD30 (strong and diffuse), CD43, and negative for ALK, CD4, CD5, CD7, CD8, CD10, CD20, CD34, CD56, TdT, PAX-5, myeloperoxidase, BCL-6, PD-1, and in situ hybridization for EBVencoded RNA (Figure 1E and F). Ki-67 proliferation index was around 90%. The bone marrow
biopsy showed involvement by similar atypical cells (Figure 1G and H), with marked (3+) increase in reticulin fibrosis (not shown). Furthermore, there was an increase in CD138-positive lambda light chain-restricted plasma cells (Figure 1H–J), accounting for around 15% of marrow elements. The overall findings were consistent with an aggressive CD30-positive T-cell neoplasm involving multiple organs with a concomitant IgA lambda-secreting plasma cell myeloma. Unfortunately, shortly after the diagnosis was made, the patient’s condition rapidly deteriorated, leading to his demise. According to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, the main differential diagnoses in this case include ALK-negative anaplastic large cell lymphoma (ALCL) and CD30-positive peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS).4 We followed the WHO conservative approach where ALK-negative ALCL should be diagnosed only in cases where the morphology and the immunophenotype are very similar to those of the ALK-positive cases.4 We believed that the overall clinical and histologic findings were more consistent with a PTCL, NOS than an ALCL or a primary cutaneous T-cell lymphoma. Interestingly, there was a concomitant plasma cell myeloma (PM) in the bone marrow. The relationship between T-cell neoplasms and PM is unclear, as various studies have described different possible mechanisms for tumorigenesis.2,3,5,6 Therefore, the chronological sequence of tumors could not be determined with certainty.
Hematol Oncol Stem Cell Ther 8(1)
First Quarter 2015
letter to editor
Figure 1. Right lower extremity (A) and left upper extremity (B) skin lesions. Superficial and deep infiltrate dermal infiltrate (H&E, 40·) (C), consisting of medium to largesized atypical cells with irregular nuclei, occasionally prominent nucleoli, variable chromatin pattern, and a high mitotic activity, sparing the epidermis (H&E, 400·) (D). Diffuse positivity for CD3 (E) and CD30 (F) in the atypical infiltrate, with no expression of CD5 or ALK (not shown). Hypercellular bone marrow diffusely involved by an atypical cell population (H&E, 40·) (G), morphologically similar to the infiltrate in the skin, admixed with clusters of plasma cells (H&E, 400·) (H). Increased plasma cells highlighted by CD138 (I) showing lambda light chain restriction (J), and negative for kappa light chains (not shown).
In summary, this case is of value because, to the best of our knowledge, it is the first reported case of a plasma cell neoplasm associated with an aggressive
Hematol Oncol Stem Cell Ther 8(1)
First Quarter 2015
CD30-positive PTCL, NOS. Reporting such cases is important as it adds to the pool of rare cases of concomitant T-cell neoplasms and plasma cell myelomas, and
might help in determining an etiological relationship, if any, between these two hematological malignancies.
41
letter to editor CONFLICT OF INTEREST/ SOURCES OF FUNDING
Center, Beirut, Lebanon * Corresponding author at:
The authors have no conflict of interest or sources of funding to disclose.
Department of Pathology and
Samer Nassif a,*, Nadim El-Majzoub a, Ossama Abbas b, Sally Temraz c, Zaher Chakhachiro a
Beirut, Lebanon. Tel.: +961 1 350
a
Department of Pathology and
Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon,
b
Laboratory Medicine, American University of Beirut Medical Center, P.O. Box 11-0236, Riad El Solh 110, 72020 000x5188; fax: +961 1 370 845. [email protected] ª 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/3.0/). DOI: http://dx.doi.org/10.1016/ j.hemonc.2014.11.004
Department of
Dermatology, American University of
REFERENCES
T-cell lymphoma in the same patient: is there a causal relation? J. Cutan. Pathol. 2011;38(3): 298–300. 2. Cartron G, Roingeard P, Benboubker L, Vaillant L, Tartas S, Delain M, et al.. Sezary syndrome in a patient with multiple myeloma: demonstration of a clonally distinct second malignancy. Eur. J. Haematol. 1999;63(5):354–7. 3. Gernone A, Frassanito MA, Pellegrino A, Vacca A, Dammacco F. Multiple myeloma and mycosis fungoides in the same patient: clinical, immunologic, and molecular studies. Ann. Hematol. 2002;81(6):326–31. 4. Mason DY, Harris NL, Delsol G, Stein H, Campo E, Kinney MC, et al.. Anaplastic large cell lymphoma, ALK-negative. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008. p. 317–9. 5. Prabhala RH, Neri P, Bae JE, Tassone P, Shammas MA, Allam CK, et al.. Dysfunctional T regulatory cells in multiple myeloma. Blood 2006;107(1):301–4. 6. Dunleavy K, Wilson WH, Jaffe ES. Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical implications. Curr. Opin. Hematol. 2007;14(4):348–53.
Beirut Medical Center, Beirut, Lebanon, c
Department of Internal Medicine,
American University of Beirut Medical
42
1. Tangour M, Chelly I, Haouet S, Zitouna M, Kchir N. Multiple myeloma and cutaneous anaplastic large
Hematol Oncol Stem Cell Ther 8(1)
First Quarter 2015
