- Email: [email protected]
An unusual cause of nodular skin lesions with ulcer
Pathology (December 2008) 40(7), pp. 714–718
TEST AND TEACH
An unusual cause of nodular skin lesions with ulcer Part 1 CRISTINE SZU LYN DING, YUK PING CHAU, HWEI YEE LEE, WAI MING YAP KHOON LEONG CHUAH
AND
Department of Pathology, Tan Tock Seng Hospital, Singapore
CASE REPORT A 51-year-old Chinese man presented to a general practitioner with a left ankle ulcer of a few weeks duration. He had no significant medical history and denied smoking or alcohol intake. There was no history of previous trauma to the limb. He was referred to a hospital and after consultation with the vascular surgeons and dermatologists, a diagnosis of chronic eczema with factitious ulceration was made. He was treated empirically with steroid cream and antibiotics. However, the ulcer persisted and enlarged over a period of 3 months, being associated with a foul smelling whitish discharge. In addition, new skin nodules appeared over the back and limbs over a period of 3 weeks in association with fever and rigors. He sought treatment at our institution. On physical examination, there was a large confluent gangrenous ulcer over the left ankle. There was no impairment of sensory or motor functions of the affected limb. Multiple cutaneous and subcutaneous nodules and
plaques with necrotic centres were present over the trunk and limbs. Otherwise, physical examination was essentially unremarkable, particularly no organomegaly or palpable lymphadenopathy was found. Blood investigations performed were unremarkable. Computed tomography (CT) scan of the thorax, abdomen and pelvis disclosed the presence of multiple enhancing cutaneous and subcutaneous nodules in the torso with minimal surrounding inflammatory change. No other abnormalities, particularly lymphadenopathy, were detected. Doppler ultrasound study indicated the absence of significant arterial disease or deep vein thrombosis of the lower limbs. An excision biopsy from a skin lesion over the upper back was subsequently performed. Following the histology report of the skin excision specimen, the patient underwent an examination by an otolaryngologist during which no lesion was detected in the nasal region. In addition, subsequent bone marrow trephine biopsy did not reveal any abnormal cellular infiltrate.
FIG. 1 (A) Low power view of the subcutaneous fat associated with an area of necrosis involving destruction of the wall of the blood vessel with fibrinoid material; (B) low power magnification disclosing an infiltrate of lymphoid cells around the skin adnexal structures (H&E, 640).
Print ISSN 0031-3025/Online ISSN 1465-3931 # 2008 Royal College of Pathologists of Australasia DOI: 10.1080/00313020802441691
TEST AND TEACH
715
Grossly, the excision specimen consisted of an ellipse of skin measuring 3.0 6 0.4 cm with underlying subcutaneous tissue measuring up to 1.7 cm in depth. The subcutaneous fat showed a tan-brown necrotic nodule measuring 1.5 6 1.2 6 0.4 cm. On histological examination, the subcutaneous fat showed areas of necrosis and infarction. The overlying epidermis was intact in the tissues submitted. There was an infiltrate of atypical medium to large lymphoid cells with prominent nucleoli and irregular nuclear outlines affecting the subcutaneous fat and around the skin adnexal structures in the dermis (Fig. 1 and 2). Some accompanying smaller lymphocytes and occasional eosinophils were noted. No epidermotropism was noted. An angiocentric distribution of the lymphoid cells in association with blood vessel wall permeation was noted (Fig. 3). In the areas of necrosis and infarction, ghost outlines of the native tissue and abnormal lymphoid cells were noted. Received 10 August, accepted 1 September 2008 See next page for explanation and diagnosis FIG. 2 An area with viable lymphoid cells insinuating in between the adipocytes (H&E, 6400).
FIG. 3 (A) Abnormal large lymphoid cells with occasional large nucleoli permeating the wall of the blood vessel. Note the presence of a mitotic figure (arrow). (B) An area of necrosis involving a blood vessel. Note the presence of outlines of lymphoid cells in the wall of the blood vessel (H&E, 6400).
716
Pathology (2008), 40(7), December
TEST AND TEACH
An unusual cause of nodular skin lesions with ulcer Part 2
EXPLANATION AND DIAGNOSIS: CUTANEOUS EXTRANODAL NK/T-CELL LYMPHOMA, NASAL TYPE On immunohistochemical staining, the abnormal lymphoid cells stained for CD3 (Fig. 4) associated with a loss of CD5 expression. The T cells stained for granzyme B (Fig. 5A) and about 50% of the T cells stained for CD30. The stain for CD56 was negative. On in situ hybridisation a significantly large proportion of the tumour cells showed positive staining for Epstein–Barr virus encoded RNA (EBER; Fig. 5B). The Ki-67 proliferation index was approximately 90%. The histological appearance in conjunction with the immunohistochemistry findings corroborated a diagnosis of extranodal NK/T-cell lymphoma, nasal type. Extranodal NK/T-cell lymphoma, nasal type, previously known as lethal midline granuloma, is a rare distinct clinico-pathological entity associated with Epstein–Barr virus (EBV) and typically results in the destruction of the midface, palatal and orbital walls.1,2 Although nasal disease is the most common site of involvement, this extranodal lymphoma has been reported in other sites such as the skin, soft tissue, testes, gastrointestinal tract and upper respiratory tract, the skin being the second most common site after the nasal/nasopharyngeal region.3 Secondary nodal involvement has been described.1,2 Cutaneous manifestation of the disease may be a primary event, as in this report, or a secondary event,3 underlining the need for appropriate clinical correlation to exclude secondary cutaneous involvement. Although most of the tumour cells express CD56 in association with EBV infection, rarely some tumours are CD56 negative associated with cytotoxic T-cell pheonotype and EBV infection, prompting the preferred term of NK/Tcell lymphoma in describing this group of lymphoid neoplasm rather than NK cell lymphoma.1,2
FIG. 4 Antibodies against CD3 decorating the tumour cells infiltrating the wall of the blood vessel (Avidin biotin complex, 6400).
Extranodal NK/T-cell lymphoma is rare in Europe and the USA4 and is more prevalent in Asia, Mexico, and Central and South America.2 It usually occurs in adult males with a median age of 50–55 years, although it has been reported that cutaneous nasal type NK/T-cell lymphoma occurs more often in females.5 Cases occurring in immunosuppressed patients and post-transplant have also been reported.1,2 The aetiology of the disease is still uncertain, although there appears to be a close association with EBV infection, which may be suggestive of a pathogenic effect.1–3 In nasal NK/T-cell lymphoma, there is almost invariable association with EBV (495%) regardless of the ethnic origin of the patient.1,2 In nasal-type NK/T-cell lymphoma, although a high prevalence of EBV in Asian patients has been reported (490%), it is not uncommon for EBV to be negative in Caucasian patients.1,6,7 In the skin, extranodal NK/T-cell lymphoma, nasal type, typically presents with tumour nodules and plaques which are often ulcerated and associated with fever, malaise and weight loss.3 Haemophagocytic syndrome may accompany the illness. There is a close relation between extranodal NK/T-cell lymphoma and NK-cell leukaemia, the latter capable of cutaneous manifestations and being similarly associated with EBV. The cytology of the tumour cells can range from minimally atypical small lymphoid cells to large or even anaplastic cells.1 In most cases, the cells tend to be medium sized or a mixture of small and large cells. The nuclei may be irregular, and the nucleoli are generally inconspicuous. The cytoplasm is commonly clear or pale and of moderate amount. In Giemsa-stained preparations, azurophilic granules can be seen in the cytoplasm. On electron microscopy, electron dense granules can be seen.1,2 On light microscopy, there is usually a dense dermal infiltrate centered around the skin appendages and blood vessels resulting in a column-like appearance on low magnification, as in our case.3 The lymphoid infiltrate typically shows angiocentricity with angiodestruction, which may be accompanied by fibrinoid changes in the blood vessels. Coagulative necrosis, frequent mitotic figures and apoptosis are usually present. Extension into the subcutaneous fat is common as in our case. Epidermotropism may be present at least focally in up to 30% of the cases. In some cases, there may be an admixture of accompanying inflammatory cells which include small lymphocytes, plasma cells, histiocytes and eosinophils, which may be mistaken for an inflammatory process.1,2 The most common characteristic immunophenotype is: CD2þ, CD56þ, surface CD3–, cytoplasmic CD3eþ and CD43þ.1–3 Expression of cytotoxic granules (T1A-1, perforin and granzyme B) is present in most cases. CD7 is sometimes expressed but other T- and NK-cell associated antigens such as CD4, CD8, CD16 and CD57 are usually negative. Some cases may express CD25 or CD30.1,2
TEST AND TEACH
717
FIG. 5 (A) The presence of cytotoxic molecules confirmed by immunohistochemistry for granzyme B (avidin biotin complex, 6600). (B) T cells showing strong signal on in situ hybridisation for EBER (6400).
Cases which are CD56 negative but cytoplasmic CD3e positive, cytotoxic molecule positive and EBV positive, as in our case, are commonly included in the category of NK/ T-cell lymphomas, nasal type, as they exhibit a similar clinical disease as cases with CD56 expression.2 However, a diagnosis of extranodal NK/T-cell lymphoma must be withheld in the absence of cytotoxic molecule expression or demonstration of EBV positivity.2,3 In cases where there is cytoplasmic CD3e positivity associated with a negative cytotoxic molecule expression and for which an association with EBV cannot be demonstrated, a diagnosis of peripheral T-cell lymphoma, unspecified, is advocated.3 In terms of differential diagnosis on histology in our case, lymphomatoid granulomatosis was considered in view of the angiocentricity and angiodestructive nature of the tumour.8 However, as lymphomatoid granulomatosis is a B-cell lymphoma associated EBV infection in a T-cell rich background, the distinction can be made on immunohistochemistry for B- and T-cell markers in association with in situ hybridisation for EBER where EBV positive B cells are seen in lymphomatoid granulomatosis. Another differential diagnosis to be considered is that of a primary cutaneous CD30þ and CD56þ anaplastic large cell lymphoma with prominent angioinvasion and nerve involvement which overlaps with NK/T-cell lymphoma and anaplastic large cell lymphoma in terms of clinicopathological characteristics.9 In addition, CD30 expression as exemplified in our case can be seen in extranodal NK/T-cell lymphoma, heightening the similarity between the two entities. However, primary cutaneous CD30þ and CD56þ anaplastic large cell lymphoma with prominent
angioinvasion and nerve involvement typically is accompanied by a massive admixture of histiocytes and neutrophils, a feature which was lacking in our case. In addition, EBV infection has not been detected in primary cutaneous CD30þ and CD56þ anaplastic large cell lymphoma with prominent angioinvasion and nerve involvement. Most cases show germline configuration of the T-cell receptor and immunoglobulin genes, suggestive of a true NK cell origin. Various cytogenetic abnormalities have been reported, the most common being del(6)(q21q25) or i(6)(p10). However, no specific chromosomal translocations have yet to be found.2 Cutaneous extranodal NK/T-cell lymphoma is a highly aggressive neoplasm with a median survival of less than 15 months.3 Extracutaneous involvement at presentation is the most important predictor of poor outcome while coexpression of CD30 and CD56 may confer a better prognosis. Recently, there have been reports of aggressive cutaneous intravascular T-cell lymphoma sharing similar EBV association, cytological appearance and immunophenotype as extranodal NK/T-cell lymphoma.10,11 Whether this implies that extranodal NK/T-cell lymphoma is capable of intravascular disease, thereby including those cases of T-cell lymphoma with NK/T-cell immunophenotype and intravascular manifestation alone into the family of extranodal NK/T-cell lymphoma, will rest on further studies of this rare but interesting lymphoid neoplasm.
Key words: Extranodal NK/T-cell lymphoma, skin, CD56, EBV.
718
TEST AND TEACH
Address for correspondence: Dr K. L. Chuah, Department of Pathology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433. E-mail: [email protected]
References 1. Chan JKC. Extranodal NK/T-cell lymphoma. In: Fletcher CDM, editor. Diagnostic Histopathology of Tumors. Philadelphia: Churchill Livingstone Elsevier, 2007; 1229–33. 2. Chan JKC, Jaffe ES, Ralfkiaer E. Extranodal NK/T-cell lymphoma, nasal type. In: Jaffe ES, Harris NL, Stein, H, et al., editors. WHO Classification of Tumors. Tumors of Hematopoietic and Lymphoid Tissue. Lyon: IARC press, 2001; 204–7. 3. Kohler S, Iwatsuki K, Jaffe ES, et al. Extranodal NK/T-cell lymphoma, nasal type. In: LeBoit PE, Burg G, Weedon D et al., editors. World Health Organization Classification of Tumours. Skin Tumours. Lyon: IARC Press, 2006; 191–2. 4. Sandner A, Helmbold P, Winkler M, et al. Cutaneous dissemination of nasal NK/T-cell lymohoma in a young girl. Clin Exp Dermatol 2008; 33: 615–8. 5. Greer JP, Kinney MC, Loughran TP. T cell and NK cell lymphoproliferative disorders. Haemotology Am Soc Hematol Educ Program 2001: 259–81.
Pathology (2008), 40(7), December
6. Ng SB, Lai KW, Murugaya S, et al. Nasal-type extranodal natural killer/T-cell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore. Mod Pathol 2004; 17: 1097– 107. 7. Slater DN. New CD56 positive and cytotoxic T-cell cutaneous lymphomas from the World Health Organisation. Br J Dermatol 2003; 148: 385–7. 8. Jaffe ES, Toro J, Wilson WH. Lymphomatoid granulomatosis. In: LeBoit PE, Burg G, Weedon D et al., editors. World Health Organization Classification of Tumours. Skin Tumours. Lyon: IARC Press, 2006; 202–3. 9. Boudova L, Kazakov DV, Jindra P, et al. Primary cutaneous histiocyte and neutrophil-rich CD30þ and CD56þ anaplastic large cell lymphoma with prominent angioinvasion and nerve involvement in the forehead and scalp of an immunocompetent woman. J Cutan Pathol 2006; 33: 584–9. 10. Kuo TT, Chen MJ, Kuo MC. Cutaneous intravascular NK-cell lymphoma: report of a rare variant associated with Epstein-Barr virus. Am J Surg Pathol 2006; 30: 1197–201. 11. Cerroni L, Massone C, Kutzner H, et al. Intravascular large T-cell or NK-cell lymphoma: a rare variant of intravascular large cell lymphoma with frequent cytotoxic phenotype and association with Epstein-Barr virus infection. Am J Surg Pathol 2008; 32: 891–8.
TEST AND TEACH
An unusual cause of nodular skin lesions with ulcer Part 1 CRISTINE SZU LYN DING, YUK PING CHAU, HWEI YEE LEE, WAI MING YAP KHOON LEONG CHUAH
AND
Department of Pathology, Tan Tock Seng Hospital, Singapore
CASE REPORT A 51-year-old Chinese man presented to a general practitioner with a left ankle ulcer of a few weeks duration. He had no significant medical history and denied smoking or alcohol intake. There was no history of previous trauma to the limb. He was referred to a hospital and after consultation with the vascular surgeons and dermatologists, a diagnosis of chronic eczema with factitious ulceration was made. He was treated empirically with steroid cream and antibiotics. However, the ulcer persisted and enlarged over a period of 3 months, being associated with a foul smelling whitish discharge. In addition, new skin nodules appeared over the back and limbs over a period of 3 weeks in association with fever and rigors. He sought treatment at our institution. On physical examination, there was a large confluent gangrenous ulcer over the left ankle. There was no impairment of sensory or motor functions of the affected limb. Multiple cutaneous and subcutaneous nodules and
plaques with necrotic centres were present over the trunk and limbs. Otherwise, physical examination was essentially unremarkable, particularly no organomegaly or palpable lymphadenopathy was found. Blood investigations performed were unremarkable. Computed tomography (CT) scan of the thorax, abdomen and pelvis disclosed the presence of multiple enhancing cutaneous and subcutaneous nodules in the torso with minimal surrounding inflammatory change. No other abnormalities, particularly lymphadenopathy, were detected. Doppler ultrasound study indicated the absence of significant arterial disease or deep vein thrombosis of the lower limbs. An excision biopsy from a skin lesion over the upper back was subsequently performed. Following the histology report of the skin excision specimen, the patient underwent an examination by an otolaryngologist during which no lesion was detected in the nasal region. In addition, subsequent bone marrow trephine biopsy did not reveal any abnormal cellular infiltrate.
FIG. 1 (A) Low power view of the subcutaneous fat associated with an area of necrosis involving destruction of the wall of the blood vessel with fibrinoid material; (B) low power magnification disclosing an infiltrate of lymphoid cells around the skin adnexal structures (H&E, 640).
Print ISSN 0031-3025/Online ISSN 1465-3931 # 2008 Royal College of Pathologists of Australasia DOI: 10.1080/00313020802441691
TEST AND TEACH
715
Grossly, the excision specimen consisted of an ellipse of skin measuring 3.0 6 0.4 cm with underlying subcutaneous tissue measuring up to 1.7 cm in depth. The subcutaneous fat showed a tan-brown necrotic nodule measuring 1.5 6 1.2 6 0.4 cm. On histological examination, the subcutaneous fat showed areas of necrosis and infarction. The overlying epidermis was intact in the tissues submitted. There was an infiltrate of atypical medium to large lymphoid cells with prominent nucleoli and irregular nuclear outlines affecting the subcutaneous fat and around the skin adnexal structures in the dermis (Fig. 1 and 2). Some accompanying smaller lymphocytes and occasional eosinophils were noted. No epidermotropism was noted. An angiocentric distribution of the lymphoid cells in association with blood vessel wall permeation was noted (Fig. 3). In the areas of necrosis and infarction, ghost outlines of the native tissue and abnormal lymphoid cells were noted. Received 10 August, accepted 1 September 2008 See next page for explanation and diagnosis FIG. 2 An area with viable lymphoid cells insinuating in between the adipocytes (H&E, 6400).
FIG. 3 (A) Abnormal large lymphoid cells with occasional large nucleoli permeating the wall of the blood vessel. Note the presence of a mitotic figure (arrow). (B) An area of necrosis involving a blood vessel. Note the presence of outlines of lymphoid cells in the wall of the blood vessel (H&E, 6400).
716
Pathology (2008), 40(7), December
TEST AND TEACH
An unusual cause of nodular skin lesions with ulcer Part 2
EXPLANATION AND DIAGNOSIS: CUTANEOUS EXTRANODAL NK/T-CELL LYMPHOMA, NASAL TYPE On immunohistochemical staining, the abnormal lymphoid cells stained for CD3 (Fig. 4) associated with a loss of CD5 expression. The T cells stained for granzyme B (Fig. 5A) and about 50% of the T cells stained for CD30. The stain for CD56 was negative. On in situ hybridisation a significantly large proportion of the tumour cells showed positive staining for Epstein–Barr virus encoded RNA (EBER; Fig. 5B). The Ki-67 proliferation index was approximately 90%. The histological appearance in conjunction with the immunohistochemistry findings corroborated a diagnosis of extranodal NK/T-cell lymphoma, nasal type. Extranodal NK/T-cell lymphoma, nasal type, previously known as lethal midline granuloma, is a rare distinct clinico-pathological entity associated with Epstein–Barr virus (EBV) and typically results in the destruction of the midface, palatal and orbital walls.1,2 Although nasal disease is the most common site of involvement, this extranodal lymphoma has been reported in other sites such as the skin, soft tissue, testes, gastrointestinal tract and upper respiratory tract, the skin being the second most common site after the nasal/nasopharyngeal region.3 Secondary nodal involvement has been described.1,2 Cutaneous manifestation of the disease may be a primary event, as in this report, or a secondary event,3 underlining the need for appropriate clinical correlation to exclude secondary cutaneous involvement. Although most of the tumour cells express CD56 in association with EBV infection, rarely some tumours are CD56 negative associated with cytotoxic T-cell pheonotype and EBV infection, prompting the preferred term of NK/Tcell lymphoma in describing this group of lymphoid neoplasm rather than NK cell lymphoma.1,2
FIG. 4 Antibodies against CD3 decorating the tumour cells infiltrating the wall of the blood vessel (Avidin biotin complex, 6400).
Extranodal NK/T-cell lymphoma is rare in Europe and the USA4 and is more prevalent in Asia, Mexico, and Central and South America.2 It usually occurs in adult males with a median age of 50–55 years, although it has been reported that cutaneous nasal type NK/T-cell lymphoma occurs more often in females.5 Cases occurring in immunosuppressed patients and post-transplant have also been reported.1,2 The aetiology of the disease is still uncertain, although there appears to be a close association with EBV infection, which may be suggestive of a pathogenic effect.1–3 In nasal NK/T-cell lymphoma, there is almost invariable association with EBV (495%) regardless of the ethnic origin of the patient.1,2 In nasal-type NK/T-cell lymphoma, although a high prevalence of EBV in Asian patients has been reported (490%), it is not uncommon for EBV to be negative in Caucasian patients.1,6,7 In the skin, extranodal NK/T-cell lymphoma, nasal type, typically presents with tumour nodules and plaques which are often ulcerated and associated with fever, malaise and weight loss.3 Haemophagocytic syndrome may accompany the illness. There is a close relation between extranodal NK/T-cell lymphoma and NK-cell leukaemia, the latter capable of cutaneous manifestations and being similarly associated with EBV. The cytology of the tumour cells can range from minimally atypical small lymphoid cells to large or even anaplastic cells.1 In most cases, the cells tend to be medium sized or a mixture of small and large cells. The nuclei may be irregular, and the nucleoli are generally inconspicuous. The cytoplasm is commonly clear or pale and of moderate amount. In Giemsa-stained preparations, azurophilic granules can be seen in the cytoplasm. On electron microscopy, electron dense granules can be seen.1,2 On light microscopy, there is usually a dense dermal infiltrate centered around the skin appendages and blood vessels resulting in a column-like appearance on low magnification, as in our case.3 The lymphoid infiltrate typically shows angiocentricity with angiodestruction, which may be accompanied by fibrinoid changes in the blood vessels. Coagulative necrosis, frequent mitotic figures and apoptosis are usually present. Extension into the subcutaneous fat is common as in our case. Epidermotropism may be present at least focally in up to 30% of the cases. In some cases, there may be an admixture of accompanying inflammatory cells which include small lymphocytes, plasma cells, histiocytes and eosinophils, which may be mistaken for an inflammatory process.1,2 The most common characteristic immunophenotype is: CD2þ, CD56þ, surface CD3–, cytoplasmic CD3eþ and CD43þ.1–3 Expression of cytotoxic granules (T1A-1, perforin and granzyme B) is present in most cases. CD7 is sometimes expressed but other T- and NK-cell associated antigens such as CD4, CD8, CD16 and CD57 are usually negative. Some cases may express CD25 or CD30.1,2
TEST AND TEACH
717
FIG. 5 (A) The presence of cytotoxic molecules confirmed by immunohistochemistry for granzyme B (avidin biotin complex, 6600). (B) T cells showing strong signal on in situ hybridisation for EBER (6400).
Cases which are CD56 negative but cytoplasmic CD3e positive, cytotoxic molecule positive and EBV positive, as in our case, are commonly included in the category of NK/ T-cell lymphomas, nasal type, as they exhibit a similar clinical disease as cases with CD56 expression.2 However, a diagnosis of extranodal NK/T-cell lymphoma must be withheld in the absence of cytotoxic molecule expression or demonstration of EBV positivity.2,3 In cases where there is cytoplasmic CD3e positivity associated with a negative cytotoxic molecule expression and for which an association with EBV cannot be demonstrated, a diagnosis of peripheral T-cell lymphoma, unspecified, is advocated.3 In terms of differential diagnosis on histology in our case, lymphomatoid granulomatosis was considered in view of the angiocentricity and angiodestructive nature of the tumour.8 However, as lymphomatoid granulomatosis is a B-cell lymphoma associated EBV infection in a T-cell rich background, the distinction can be made on immunohistochemistry for B- and T-cell markers in association with in situ hybridisation for EBER where EBV positive B cells are seen in lymphomatoid granulomatosis. Another differential diagnosis to be considered is that of a primary cutaneous CD30þ and CD56þ anaplastic large cell lymphoma with prominent angioinvasion and nerve involvement which overlaps with NK/T-cell lymphoma and anaplastic large cell lymphoma in terms of clinicopathological characteristics.9 In addition, CD30 expression as exemplified in our case can be seen in extranodal NK/T-cell lymphoma, heightening the similarity between the two entities. However, primary cutaneous CD30þ and CD56þ anaplastic large cell lymphoma with prominent
angioinvasion and nerve involvement typically is accompanied by a massive admixture of histiocytes and neutrophils, a feature which was lacking in our case. In addition, EBV infection has not been detected in primary cutaneous CD30þ and CD56þ anaplastic large cell lymphoma with prominent angioinvasion and nerve involvement. Most cases show germline configuration of the T-cell receptor and immunoglobulin genes, suggestive of a true NK cell origin. Various cytogenetic abnormalities have been reported, the most common being del(6)(q21q25) or i(6)(p10). However, no specific chromosomal translocations have yet to be found.2 Cutaneous extranodal NK/T-cell lymphoma is a highly aggressive neoplasm with a median survival of less than 15 months.3 Extracutaneous involvement at presentation is the most important predictor of poor outcome while coexpression of CD30 and CD56 may confer a better prognosis. Recently, there have been reports of aggressive cutaneous intravascular T-cell lymphoma sharing similar EBV association, cytological appearance and immunophenotype as extranodal NK/T-cell lymphoma.10,11 Whether this implies that extranodal NK/T-cell lymphoma is capable of intravascular disease, thereby including those cases of T-cell lymphoma with NK/T-cell immunophenotype and intravascular manifestation alone into the family of extranodal NK/T-cell lymphoma, will rest on further studies of this rare but interesting lymphoid neoplasm.
Key words: Extranodal NK/T-cell lymphoma, skin, CD56, EBV.
718
TEST AND TEACH
Address for correspondence: Dr K. L. Chuah, Department of Pathology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433. E-mail: [email protected]
References 1. Chan JKC. Extranodal NK/T-cell lymphoma. In: Fletcher CDM, editor. Diagnostic Histopathology of Tumors. Philadelphia: Churchill Livingstone Elsevier, 2007; 1229–33. 2. Chan JKC, Jaffe ES, Ralfkiaer E. Extranodal NK/T-cell lymphoma, nasal type. In: Jaffe ES, Harris NL, Stein, H, et al., editors. WHO Classification of Tumors. Tumors of Hematopoietic and Lymphoid Tissue. Lyon: IARC press, 2001; 204–7. 3. Kohler S, Iwatsuki K, Jaffe ES, et al. Extranodal NK/T-cell lymphoma, nasal type. In: LeBoit PE, Burg G, Weedon D et al., editors. World Health Organization Classification of Tumours. Skin Tumours. Lyon: IARC Press, 2006; 191–2. 4. Sandner A, Helmbold P, Winkler M, et al. Cutaneous dissemination of nasal NK/T-cell lymohoma in a young girl. Clin Exp Dermatol 2008; 33: 615–8. 5. Greer JP, Kinney MC, Loughran TP. T cell and NK cell lymphoproliferative disorders. Haemotology Am Soc Hematol Educ Program 2001: 259–81.
Pathology (2008), 40(7), December
6. Ng SB, Lai KW, Murugaya S, et al. Nasal-type extranodal natural killer/T-cell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore. Mod Pathol 2004; 17: 1097– 107. 7. Slater DN. New CD56 positive and cytotoxic T-cell cutaneous lymphomas from the World Health Organisation. Br J Dermatol 2003; 148: 385–7. 8. Jaffe ES, Toro J, Wilson WH. Lymphomatoid granulomatosis. In: LeBoit PE, Burg G, Weedon D et al., editors. World Health Organization Classification of Tumours. Skin Tumours. Lyon: IARC Press, 2006; 202–3. 9. Boudova L, Kazakov DV, Jindra P, et al. Primary cutaneous histiocyte and neutrophil-rich CD30þ and CD56þ anaplastic large cell lymphoma with prominent angioinvasion and nerve involvement in the forehead and scalp of an immunocompetent woman. J Cutan Pathol 2006; 33: 584–9. 10. Kuo TT, Chen MJ, Kuo MC. Cutaneous intravascular NK-cell lymphoma: report of a rare variant associated with Epstein-Barr virus. Am J Surg Pathol 2006; 30: 1197–201. 11. Cerroni L, Massone C, Kutzner H, et al. Intravascular large T-cell or NK-cell lymphoma: a rare variant of intravascular large cell lymphoma with frequent cytotoxic phenotype and association with Epstein-Barr virus infection. Am J Surg Pathol 2008; 32: 891–8.