Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

Abstract

Multiple lymphomatous polyposis (MLP) is an unusual form of non-Hodgkin’s lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL is reviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

Key Words: Adult T-cell leukemia/lymphoma, Multiple lymphomatous polyposis, Human T-cell lymphotropic virus type 1, Strongyloides stercoralis, Colonoscopy

INTRODUCTION

Table 1 Clinical features and colonic findings of adult T-cell leukemia/lymphoma reported in the English literature.

Author	Age/gender	Gastroduodenal findings	Colonic findings	Treatment	Outcome
Utsunomiya[5]	55/M	Gastric small nodules	Edematous mucosa	ND	ND
	55/M	Gastric redness and petechiae	Diffuse petechiae	ND	ND
	67/M	Gastric ulcer and erosions	Granular appearance	ND	ND
	49/M	Gastroduodenal erosions	MLP	ND	ND
Tokunaga[8]	60/M	ND	Ulcerated tumor	ND	15 mo, died
Itsuno[9]	43/M	Gastric ulcerated tumors	MLP	CPA, DXR, VCR	8 mo, died
Gakiya[10]	62/M	Duodenal MLP	MLP	CPA, PSL	1 mo, alive
Isomoto[11]	70/M	Duodenal polypoid tumor	MLP	CPA, DXR, VDS, VP-16	4 mo, alive
Isomoto[12]	47/M	Gastric protruding masses	Granular, friable, and hyperemic mucosa	CPA, DXR, VCR, PSL	12 mo, died
Isomoto[13]	58/F	Normal	MLP	CPA, DXR, VDS	7 mo, died
Asada[14]	78/F	ND	Reddish, flat or slightly elevated lesion	CPA, THP, VCR, VP-16	died
Hidaka[15]	68/M	ND	Ulcerated tumor	surgery, CPA, DXR, VDS, PSL	10 mo, alive
Onishi[16]	41/F	ND	Redness and erosion	ND	ND
Present case	68/M	NE	MLP	CPA, DXR, VCR, PSL	3 mo, died

MLP: Multiple lymphomatous polyposis; ND: Not described; NE: Not examined; CPA: Cyclophosphamide; DXR: Doxorubicin; VCR: Vincristine; VDS: Vindesine; PSL: Prednisolone; THP: Pirarubicin.

Figure 1 Colonoscopic images of the transverse colon. A: Multiple small polypoid lesions were presented; B: Closer observation revealed tiny submucosal tumors as well as whitish polypoid lesions.

Figure 2 Colonoscopic images with indigo carmine dye. A: Multiple lymphomatous polyposis was clearly depicted; B: Closer observation revealed polypoid and aphthoid lesions had tiny central depression.

Figure 3 Pedunculated colonic mucosal tissue. Biopsy specimens of the polypoid lesion showing diffuse proliferation of atypical lymphoid cells in the mucosal layer (A, HE, × 100). The lymphoma cells display pleomorphic nuclei and pale cytoplasm. (B, HE, × 400).

Figure 4 Immunohistochemical studies. The lymphoma cells were positive for CD3 (A, × 400), CD25 (B, × 400) and CD30 (C, × 400), consistent with ATLL, anaplastic large cell variant.

Adult T-cell leukemia/lymphoma (ATLL) is a malignancy associated with retrovirus, human T-cell lymphotropic virus type 1 (HTLV-1)[1-3]. Although it is well-known that ATLL cells infiltrate into systemic organs including gastrointestinal (GI) tract[4], colonic involvement has not been fully documented[5]. We herein report a case of ATLL presenting MLP and provide a literature review on this rare entity.

CASE REPORT

A 48-year-old man presented with fever and watery diarrhea of a history for three weeks. He had been diagnosed as having smouldering ATLL with erythematopapular cutaneous lesions, in which monoclonal integration of proviral DNA of HTLV-1 into the host genome was confirmed by the Southern blot analysis. He had been managed conservatively without leukemic change or visceral invasion for 20 years. Physical examination revealed mandibular lymphadenopathy and multiple erythema and papules on the skin of face, abdomen and back. Abdominal examination showed hyper bowel sounds, but no hepatosplenomegaly. The white blood cell count was 7600/mm³ (normal: 3500-8000/mm³), with a normal differential. Serum lactate dehydrogenase and calcium were normal. The soluble interleukin 2 receptor was 23 070 U/mL (normal: 220-530 U/mL) and anti-HTLV-1 antibody was positive. Stool cultures and parasites including Strongyloides stercoralis were negative. Colonoscopy disclosed multiple whitish polyps throughout the colon (Figure 1). Indigo carmine dye spraying showed a central depression on the polyps (Figure 2). Pedunculated colonic mucosal tissue was replaced by diffuse proliferation of large lymphoid cells with pleomorphic nuclei and pale cytoplasm (Figure 3). Immunohistochemically, these cells were positive for CD3, CD25, and CD30, but not for CD20, suggesting anaplastic large cell variant of ATLL (Figure 4). All of these findings indicated the diagnosis of anaplastic variant of ATLL with colonic involvement presenting MLP. Subsequent ATLL infiltration to the heart, lungs and central nervous system occurred rapidly. An esophagogastroduodenoscopy was not performed. Despite combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone, the patient died 3 mo later.

DISCUSSION

HTLV-1 infection is endemic in southern Japan, Caribbean, West Africa, South America, and the Middle East. Worldwide 10-20 million people are infected approximately[1,2]. Although the majority of HTLV-1 carriers remain asymptomatic, the virus is associated with severe diseases that can be subdivided into three categories: neoplastic diseases (ATLL and cutaneous T-cell lymphoma), inflammatory syndromes (HTLV-1 myelopathy, uveitis, arthropathy, polymyositis and thyroiditis), and opportunistic infections (S. stercoralis hyperinfection, scabies, tuberculosis and leprosy)[1,2].

ATLL is a systemic multiple lymphoma with a strong tendency to infiltrate various organs or to manifest as leukemic change. Based on the disease manifestations, ATLL is classified into four subtypes: smouldering type, chronic type, lymphoma type, and acute type[6]. Disease progression to the acute or lymphoma from in patients with smouldering and chronic ATLL sometimes occurs, which has a poor prognosis with median survival time of less than 1 year. The case we present was smouldering ATLL with progression to the lymphoma form. A study of 47 autopsied patients with ATLL revealed that tumor cells infiltrate various organs including the spleen (85.1%), bone marrow (72.3%), lungs (72.3%), and GI tract (70.2%). In the GI tract, the stomach is most frequently involved (40.4%), followed by the colon (38.3%) and the small intestine (34.0%)[4]. Precise mechanisms for ATLL cell infiltration in GI tract have not been clarified; however, Chen et al[7] described that ATLL cells from patients with GI tract involvement showed considerably higher expression of an adhesion molecule integrin β7, suggesting a critical role of this molecule in adhesion and subsequent infiltration of a certain type of ATLL cells into intestinal mucosa. Regarding colonic lesions, Utsunomiya et al[5] first described radiographic and endoscopic manifestations of colonic involvement of ATLL in the English literature. They classified the colonic lesions into three types: Edema with erosion, granular appearance, and multiple polypoid lesions with central depression. Table 1 shows colonic involvement of ATLL reported in the English literature. In addition to the prior categories, tumor type[8,15] and colitis type[12] have been reported. A search of the MEDLINE database retrieved only 5 reported cases of ATLL with MLP[5,9-11,13]. Although the molecular mechanisms which may influence phenotypes of colonic lesions have not been clarified, colonic MLP may be correlated with coexistence of upper gastrointestinal MLP or polypoid lesions (Table 1). In addition, patterns and degree of ATLL cell infiltration have been suspected to be reflected to the morphological differences[17]. MLP was coined by Cornes, in 1961, to describe polypoid involvement of long segments of the gastrointestinal tract by lymphoma[17]. Although most of MLP were observed in cases with mantle cell lymphoma (MCL) of B-cell type[18-20], recent studies have shown that follicular lymphoma (FL) and mucosa-associated lymphoid tissue (MALT) lymphoma cases also showed MLP with emphasis of the importance of differentiating MCL, FL and MALT presenting MLP because of distinct prognosis among them[21]. Based on prior reports, definite differences of endoscopic morphology have not been observed between MLP of various types of lymphoma. ATLL may have the worst prognosis of MLP; therefore, pathological diagnosis will be much more important.

Patients with ATLL are immunocompromised and develop opportunistic infections that complicate the disease course[2]. Among these infections, there is an increasing body of evidence regarding a strong association between HTLV-1 and S. stercoralis co-infection[22]. Endemic region of HTLV-1 is overlapped with that of S. stercoralis worldwide and co-infestation by S. stercoralis can be severe and fatal[23]. Therefore, great attention should be paid to immunocompromised ATLL patients with refractory diarrhea and malabsorption to differentiate ATLL colonic lesions from opportunistic infectious enterocolitis caused by S. stercoralis, Entamoeba histolytica, Isospora belli, cytomegalovirus, or Mycobacterium tuberculosis.

The prognosis of ATLL is still poor with a median survival of less than one year for the acute and lymphoma forms despite advanced therapy including new multiagent chemotherapy, allogenic hematopoietic stem cell transplantation, and antiretroviral therapy[1,2]. Especially, gastrointestinal involvement of ATLL was reported to be one of the poor prognostic factors in acute type ATLL[11,24]. Therefore, endoscopic evaluation may be important for estimating prognosis of ATLL patients.

In conclusion, although this condition is rare, ATLL should be included in the differential diagnosis of MLP. We also emphasize the importance of endoscopic evaluation to differentiate neoplastic intestinal lesions from infectious enterocolitis for abdominal symptoms in patients with leukemia/lymphoma.