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Year : 2014  |  Volume : 4  |  Issue : 1  |  Page : 50-53

Primary ALK positive Anaplastic large cell lymphoma of T-cell type of jejunum: Report of a rare extranodal entity with review of literature

1 Consultant Histopathologist, Department of Histopathology, SRM Institute for Medical Sciences, Chennai, Tamil Nadu, India
2 Senior Consultant and Head of Histopathology, SRM Institute for Medical Sciences, Chennai, Tamil Nadu, India

Date of Web Publication14-Jul-2014

Correspondence Address:
Niamathullah Sadiya
Department of Histopathology, New No 21, Flat no T1, Ameer Regency, Balaji Nagar, 2nd Street, Royapettah, Chennai - 600 014, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-9596.136716

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The gastrointestinal tract (GI tract) is the most common site for extranodal lymphomas with the majority of the non-Hodgkin's B-cell type. It involves any part of the GI, the most frequent sites in the order of occurrence are the stomach, small intestine, and ileocecal region. A 17-year-old male presented with intermittent abdominal pain, altered bowel habits associated with vomiting of 1 month duration. Computerized tomography of the abdomen revealed an eccentric mass in the jejunum with significant luminal narrowing. Limited resection of jejunum showed an intraluminal polypoidal growth with a homogenous cut surface. Microscopic examination of the mass revealed a diffusely infiltrating monotonous population of large lymphoid cells with round to oval vesicular nucleus, prominent nucleoli and moderate to scanty cytoplasm, admixed with few multinucleated giant cells with wreath like arrangement of nuclei, binucleated cells, and atypical mitosis. The tumor was involving the submucosa, infiltrating the muscularis propria and extending into the sub serosa. Immunohistochemistry showed diffuse positivity for CD45, CD30, anaplastic lymphoma kinase-1 (ALK-1), and focal positivity for CD43. The immunohistochemical stains for B-cell lineage CD20, CD79a, T-cell markers CD3, CD2, CD4, CD8, CD7, and other markers namely bcl2, bcl6, CD5, CD138, CD56, Mum1, and PAX-5 were negative. Six lymph nodes isolated showed features of reactive follicular hyperplasia and were free of tumor. A diagnosis of primary ALK positive anaplastic large cell lymphoma of T-cell type of jejunum was made. Patient has completed three cycles of chemotherapy comprising of cyclophosphamide, prednisone, vincristine, and doxorubicin and is in remission until the last follow-up.

Keywords: Anaplastic lymphoma kinase positive lymphoma, jejunum, large cell lymphoma, T-cell lymphoma

How to cite this article:
Sadiya N, Ghosh M. Primary ALK positive Anaplastic large cell lymphoma of T-cell type of jejunum: Report of a rare extranodal entity with review of literature. Arch Int Surg 2014;4:50-3

How to cite this URL:
Sadiya N, Ghosh M. Primary ALK positive Anaplastic large cell lymphoma of T-cell type of jejunum: Report of a rare extranodal entity with review of literature. Arch Int Surg [serial online] 2014 [cited 2024 Mar 1];4:50-3. Available from:

  Introduction Top

The gastrointestinal tract (GI) tract is the most common site for extranodal lymphomas accounting for 5-20% of all extranodal lymphomas, [1] and the majority being of non-Hodgkin's lymphoma (NHL) type. Primary gastrointestinal lymphoma however is very rare, constituting only about 1-4% of all gastrointestinal malignancies. Although, lymphomas can arise from virtually any region of the GI tract, the most commonly involved sites are stomach followed by the small intestine and ileocecal region.

Histologically, almost 90% of primary gastrointestinal lymphomas are of B-cell lineage with very few T-cell lymphomas and Hodgkin's lymphomas. Certain histological subtypes have been noted to have a relative predilection site such as mucosa associated lymphoid tissue lymphoma in stomach, mantle cell lymphoma in the terminal ileum, jejunum and colon, as well as enteropathy associated T-cell lymphoma (EATL) in the jejunum, and follicular lymphoma in the duodenum with a geographic variation in its distribution. [2] Primary malignant tumors of the small bowel are very rare accounting for <2% of all gastrointestinal malignancies. T-cell lymphoma of the small intestine accounts for approximately 10-25% of all primary intestinal lymphomas, and primarily occurring as EATL, and most of them are often complicated by Crohn's disease. [2] The clinical presentation of small intestinal lymphomas is nonspecific and the patient has symptoms such as colicky abdominal pain, nausea, vomiting, weight loss, and rarely acute obstructive symptoms, intussusception, perforation, or diarrhea.

  Case Report Top

A 17-year-old male patient presented with a history of intermittent abdominal pain, altered bowel habits associated with vomiting of 1 month duration. Hematological and biochemical parameters were within the normal limits. Computerized tomography (CT) scan of the abdomen revealed a well-defined homogenously enhancing eccentric mass involving 7-8 cm segment of jejunum with significant luminal narrowing [Figure 1]. Multiple mesenteric lymph nodes were seen adjacent to the mass, largest measuring 15 mm × 10 mm. Patient underwent a limited resection of jejunum that was measuring 18 cm × 3 cm. Cut surface revealed an intraluminal polypoidal growth measuring 5.5 cm in maximum dimension with a grey white firm homogenous cut surface [Figure 2]. The corresponding serosa adjacent to the mass was unremarkable. Six tiny lymph nodes ranging in size from 0.5 to 1 cm were isolated. Microscopic examination revealed a diffusely infiltrating tumor involving the sub mucosa [Figure 3]a the muscularis propria and extending into the sub serosa [Figure 3]b. The tumor was composed of monotonous population of large atypical anaplastic lymphoid cells with round to oval vesicular type of nucleus, showing prominent nucleoli, and moderate to scanty cytoplasm [Figure 4] with atypical mitosis [Figure 4] inset]. Few multinucleated giant cells with a wreath like arrangement of nuclei and binucleated cells with similar morphology was also evident. Immunohistochemistry done showed diffuse positivity for CD45 [Figure 5]a, focal positivity for CD43 [Figure 5]b and epithelial membrane antigen (EMA), diffuse positivity for CD30 [Figure 5]c and anaplastic lymphoma kinase-1 (ALK-1) [Figure 5]d. The rest of the immunohistochemical stains CD20, CD79a (B-cell markers) CD3, CD2, CD4, CD7, CD8 (T-cell markers), and other markers bcl 2, bcl 6, CD56, CD5, Mum1, CD138, and PAX-5 were negative. Ki-67 proliferative index was 40%. The six lymph nodes isolated in the immediate vicinity of the mass showed reactive follicular hyperplasia.
Figure 1: Computerized tomography scan of the abdomen showing a well-defined homogenously enhancing eccentric mass lesion involving the jejunum (depicted by the white arrow) with adjacent tiny lymph nodes in the immediate vicinity of the mass (depicted by the black arrow)

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Figure 2: Gross photograph showing resected specimen of jejunum with an intraluminal polypoidal growth of 5.5 cm in maximal dimension, with a homogenous cut surface

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Figure 3: (a and b) Microphotograph showing diffuse infiltration of sub mucosa, muscularis propria and subserosa by lymphoid neoplasm (H and E, ×10)

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Figure 4: Microphotograph showing large atypical lymphoid cells with indented vesicular type of nucleus, prominent nucleoli, with scanty cytoplasm and inset showing atypical mitosis (depicted by an arrow) (H and E, ×40)

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Figure 5: (a) Diffuse membrane positivity for CD45, (b) focal membrane positivity for CD43, (c) diffuse membrane positivity for CD30, (d) diffuse cytoplasmic positivity for anaplastic lymphoma kinase-1

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A diagnosis of primary ALK positive anaplastic large cell lymphoma (ALCL) of T-cell type of Jejunum was made, as the bulk of the tumor was present in the jejunum according to Dawson's criteria. It was categorized as stage I disease as per American Joint Committee on Cancer staging protocol since the tumor was localized to the jejunum with absent bone marrow and nodal involvement on abdominal CT. Patient has completed three cycles of chemotherapy comprising of cyclophosphamide, prednisone, vincristine, and doxorubicin and is in remission.

  Discussion Top

Since the recognition of ALCL by Stein et al., [3] nodal ALCL has come to be accepted as a clinicopathologic entity. Currently, three distinct T-cell tumors, ALK positive ALCL, ALK negative ALCL, and primary cutaneous ALCL (C-ALCL) are described in 2008 World Health Organization classification. [4] ALCL represents approximately 2% of large cell NHL [5] and accounts for 3% of adult NHL and 10-20% of childhood lymphoma. It is characterized histologically by syncytial aggregates of large anaplastic cells with strong expression of CD30 in a membranous and Golgi pattern. [3]

Among the extranodal sites, the most common site of involvement is skin which is involved in 10-20% of patients. [6] Primary ALCL arising from extranodal sites other than skin are distinctively rare and have not received much attention in the literature. These sites include lung, liver, [6] spleen, [6] bone, [7] alimentary tract, [8] and pleura. [6],[9] Primary involvement of extranodal CD30 positive ALCL is less frequent than the primary nodal counterpart. [9] Involvement of the gut and central nervous system (CNS) is rare. Extranodal ALCL is less well understood, with the exception of those that arise in the skin. The rarity of ALCL of the bowel also is underscored by the fact that large cell lymphomas with anaplastic histologic features have been reported to represent only 3% of all gastrointestinal lymphomas. [8]

The majority of patients with intestinal T-cell lymphomas have a history of enteropathy. The frequent coexistence of intestinal T-cell lymphoma and malabsorptive syndrome with villous atrophy of jejunal mucosa, intra epithelial lymphocytosis, alteration in the villous crypt ratio prompted their designation as EATL. [10] However, our case did not have evidence of enteropathy and showed ALK overexpression, we prefer designation of this neoplasm as primary ALK positive ALCL of the small intestine.

Anaplastic lymphoma kinase expression by immunohistochemistry is related to t(2;5), (p23;q35) chromosomal translocation where ALK gene on chromosome 2, fuses with the nucleophosmin (NPM) gene on chromosome 5 resulting in the expression of p80 chimeric protein the NPM/ALK transcript. In 1995, Shiota et al., [11] first reported that ALK expression influences the prognosis of systemic ALCL. A case series study of primary ALCL of the small intestine by Carey et al., [12] on follow-up revealed no evidence of residual disease in one of the four patients with expression of ALK-1 by immunohistochemistry, as in our patient, in contrast to the other cases with negative expression of ALK-1. Gascoyne et al., [13] in 1999 reported that the ALK positive systemic ALCL patients have a better prognosis of 79.8% 5 year survival rate, compared to a rate of 32.9% for other ALK negative systemic ALCL patients although the clinical behavior of individual patients remains unpredictable.

Primary ALCL of the gut and CNS is rare. [14] The great majority of ALCL, ALK positive lymphomas express one or more T-cell antigens; however, due to loss of several pan T-cell antigens, some cases may have an apparent "null cell phenotype," but show evidence for a T-cell lineage at the genetic level. As no other distinction can be found in cases with a T-cell versus a null cell phenotype/null cell ALCL, ALK positive lymphoma is considered as a single entity. [15] CD3, the most widely used pan T-cell marker is negative in more than 75% of cases. [15]

The main differential considered was ALK positive ALCL, B-cell lymphoma a rare distinct diffuse large B-cell lymphoma expressing ALK protein resembling ALCL due to the sinusoidal growth pattern, express EMA, CD138, but lack CD30, showed weak to negative expression with CD45 and negative expression for conventional B-cell markers, namely CD20 and CD79a. PAX-5, which encodes B-cell lineage, and expressed in the nucleus of B-cell lymphocytes is positive, but in our case, PAX-5 done was negative with negative expression for CD138. The positivity for ALK ruled out the other differential of ALK negative ALCL, which though histologically mimics the former, but is distinctly different in showing negative expression for ALK. CD56 done was also negative. Suzuki et al., [16] have studied the expression of CD56 in ALK positive lymphoma and have found that negative expression for CD56 is associated with better prognosis than CD56 positive cases.

The strong expression for CD45, CD30, and ALK-1 with focal positivity for CD43 and negative expression for CD3, CD4, CD8, CD20, CD79a, EMA, CD138, and PAX-5 in our patient favored a diagnosis of ALK positive ALCL of T/null cell phenotype. It was categorized as Primary Jejunal Lymphoma as per Dawson's criteria, in view of

  1. Absence of peripheral lymphadenopathy at the time of presentation.
  2. Lack of enlarged mediastinal lymph nodes.
  3. Normal total and differential white blood cell count.
  4. Predominance of bowel lesion at the time of laparotomy, with only lymph nodes obviously affected in the immediate vicinity and
  5. No lymphomatous involvement of liver and spleen.

  Conclusion Top

Primary ALK positive T-cell ALCL is rare in the GI. The expression of ALK protein by immunohistochemistry is associated with a good prognosis. It needs to be differentiated from EATL and ALK positive large B-cell lymphoma. The prognosis of ALK positive ALCL is better than the ALK negative ALCL of T/null cell phenotype. The goal of this case report is to highlight the rarity of its site of presentation, the differential diagnosis and prognosis of this rare extranodal entity.

  References Top

1.Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer 1972;29:252-60.  Back to cited text no. 1
2.Ko YH, Karnan S, Kim KM, Park CK, Kang ES, Kim YH, et al. Enteropathy-associated T-cell lymphoma - A clinicopathologic and array comparative genomic hybridization study. Hum Pathol 2010;41:1231-7.  Back to cited text no. 2
3.Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: Evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 1985;66:848-58.  Back to cited text no. 3
4.Delsol G, Falini B, Muller-Hermelink HK, et al. Anaplastic large cell lymphoma (ALCL), ALK-positive. In: Swerdlow SH, Campo E, Harris NL, et al, editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 312-6.  Back to cited text no. 4
5.Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: Clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998;16:2780-95.  Back to cited text no. 5
6.Greer JP, Kinney MC, Collins RD, Salhany KE, Wolff SN, Hainsworth JD, et al. Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma. J Clin Oncol 1991;9:539-47.  Back to cited text no. 6
7.Chan JK, Ng CS, Hui PK, Leung WT, Sin VC, Lam TK, et al. Anaplastic large cell Ki-1 lymphoma of bone. Cancer 1991;68:2186-91.  Back to cited text no. 7
8.Griesser H, Henry M, Boie C, Banerjee D. Large-cell anaplastic lymphoma of the gastrointestinal tract: An immuno- and genotypic study on archival material. Hematol Pathol 1994;8:121-34.  Back to cited text no. 8
9.Chott A, Kaserer K, Augustin I, Vesely M, Heinz R, Oehlinger W, et al. Ki-1-positive large cell lymphoma. A clinicopathologic study of 41 cases. Am J Surg Pathol 1990;14:439-48.  Back to cited text no. 9
10.Chott A, Vesely M, Simonitsch I, Mosberger I, Hanak H. Classification of intestinal T-cell neoplasms and their differential diagnosis. Am J Clin Pathol 1999;111 1 Suppl 1:S68-74.  Back to cited text no. 10
11.Shiota M, Nakamura S, Ichinohasama R, Abe M, Akagi T, Takeshita M, et al. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: A distinct clinicopathologic entity. Blood 1995;86:1954-60.  Back to cited text no. 11
12.Carey MJ, Medeiros LJ, Roepke JE, Kjeldsberg CR, Elenitoba-Johnson KS. Primary anaplastic large cell lymphoma of the small intestine. Am J Clin Pathol 1999;112:696-701.  Back to cited text no. 12
13.Gascoyne RD, Aoun P, Wu D, Chhanabhai M, Skinnider BF, Greiner TC, et al. Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood 1999;93:3913-21.  Back to cited text no. 13
14.Stein H, Foss HD, Dürkop H, Marafioti T, Delsol G, Pulford K, et al. CD30 (+) anaplastic large cell lymphoma: A review of its histopathologic, genetic, and clinical features. Blood 2000;96:3681-95.  Back to cited text no. 14
15.Benharroch D, Meguerian-Bedoyan Z, Lamant L, Amin C, Brugières L, Terrier-Lacombe MJ, et al. ALK-positive lymphoma: A single disease with a broad spectrum of morphology. Blood 1998;91:2076-84.  Back to cited text no. 15
16.Suzuki R, Kagami Y, Takeuchi K, Kami M, Okamoto M, Ichinohasama R, et al. Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype. Blood 2000;96:2993-3000.  Back to cited text no. 16


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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