Int J Colorectal Dis DOI 10.1007/s00384-014-2033-5
LETTER TO THE EDITOR
Langerhans cell histiocytosis with anorectal involvement: a rare manifestation of adult disease Joshua Waters & Alyssa Fajardo & Bryan Holcomb & Virgilio George & Bruce Robb & Matthew Ziegler
Accepted: 9 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Editor: Langerhans’ cell histiocytosis (LCH) is a rare disorder of unknown etiology that is characterized by abnormal proliferation of Langerhans cells derived from the bone marrow [1, 2]. The Langerhans cell histiocytoses are defined by clonal proliferations of histiocytes, which are antigen-presenting dendritic cells. These cells are usually readily seen in the skin but can be identified in other organs, including bone, lungs, GI tract, liver, spleen, lymph nodes, and central nervous system. The affected cells have abundant and often vacuolated cytoplasm, with oval or indented nuclei. They are also characterized by the presence of Birbeck granules in the cytoplasm [1]. Colon involvement in LCH has been documented but has been historically thought to be uncommon, with incidence estimates ranging from 2 to 13 % [1]. Reported symptoms with colonic involvement have included diarrhea, rectal bleeding, failure to thrive, hypoalbuminemia, and protein-losing enteropathy [1]. Although GI tract involvement of LCH is rare, it is felt to be probably more common than previously recognized and is likely underdiagnosed because of the nonspecific presenting symptoms. Knowledge of this pathologic entity may help to ensure proper follow-up and further testing to assess for systemic disease [1]. Like Crohn’s disease, LCH involvement of the gastrointestinal tract can occur from the oral mucosa to the anal canal and perianal skin. It is unclear, however, whether perianal skin involvement is a manifestation of cutaneous or gastrointestinal disease [1]. Both Crohn’s disease and LCH can present with the finding of ulcerative lesions on colonoscopy, making pathology review of colon biopsies important for the J. Waters : A. Fajardo : B. Holcomb : V. George : B. Robb : M. Ziegler (*) Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA e-mail: [email protected]
diagnosis [2]. In addition, colon involvement of LCH can also manifest as colon polyps. Immunohistochemistry reveals Langerhans cells that are positive for CD1a and S100 protein [2]. Our colon and rectal surgery group recently took care of a 32-year-old male with a history of LCH who had initially presented over a decade ago with multiple perianal wounds and ulcerations, for which he underwent numerous excisions and biopsies. The biopsies revealed that cells of the histiocytic infiltrate were positive for CD1a and S100 protein. In 2004, he underwent a laparoscopic diverting colostomy for these nonhealing perianal ulcers. He was then lost to follow-up for many years but ultimately presented back with complaints of significant pain and pressure in his rectum that had been getting worse over the previous 4 months. He described the pain as dull and burning, and it increased in intensity with standing. He also stated that he no longer had an opening at his anus. On abdominal examination, he was noted to have a widely patent colostomy and no significant distention or tenderness during palpation. On perineal examination, however, no discrete anal opening was able to be identified, and the anal verge had been replaced by scar tissue. A CT scan of the abdomen and pelvis was performed and showed circumferential rectal wall thickening with an intraluminal stool ball but no adjacent inflammation. In addition, he was found to have mixed lytic and sclerotic lesions of the pelvic bones consistent with his history of Langerhans cell histiocytosis. Given his symptoms of increasing pelvic pressure and discomfort, he was ultimately taken to the operating room for a laparoscopic abdominoperineal resection. At surgery, he had a large impacted stool ball within the rectal lumen making mobilization of the rectum difficult. The traditional landmarks for the perineal portion of the dissection were distorted secondary to scarring and obliteration of the anus. The patient recovered well from surgery and his postoperative course was uneventful. Final pathology showed
Int J Colorectal Dis
benign rectal mucosa with surface denudation, muscularis propria smooth muscle hyperplasia, and obliteration of the anal canal. LCH that affects the colon is a rare manifestation of this pathologic process, and rectal disease is even less common. A 1999 review study identified 14 total patients reported in the literature with LCH of the colon, five of whom had rectal involvement [1]. Each of these rectal LCH patients was diagnosed in infancy and died at a young age. A 2010 review from India presented 39 total cases of GI tract involvement in LCH in the world literature, including two from their own institution [3]. Ten of these 39 patients (25.6 %) had rectal or anal biopsies that were positive for LCH. Of these ten patients with rectal involvement, nine died in infancy or early childhood. The tenth patient was noted to be in complete remission at 3month follow-up [3]. Johns Hopkins University published a review of their gastrointestinal tract LCH cases in 2011 which included ten adults and two children. This represented the largest series to date of adult GI tract LCH [4]. Eight of the ten adults presented with a solitary polyp and half of them were asymptomatic at presentation. Only one of the adults had an ulcerative lesion at the anus; the remainder had pathology confined to the stomach, small intestine, and colon [4]. Treatment for multisystem LCH has predominantly involved chemotherapy [2]. The LCH II trial results demonstrated that an effective first-line treatment for LCH includes vinblastine, prednisolone, and/or etoposide. 2-chlorodeoxyadenosine (2-CDA) may be used as second-line therapy. Patients with multi-system disease who fail conventional treatment may be candidates for stem cell transplantation [3]. In spite of these treatment options, 59 % of patients with gastrointestinal tract LCH involvement die within 18 months of diagnosis. These patients tend to have a high frequency of protein-losing enteropathy (77 %) which portends a poor prognosis [2]. Clearly, there is a significant difference in the presentation and outcome between adult and childhood LCH that involves the GI tract. Pediatric cases tend to be associated
with systemic disease and poor prognosis, and modern medical treatment for this population has been disappointing. Treatment of disseminated disease in children should not be delayed and any digestive symptoms in patients with LCH warrant an evaluation with colonoscopy. On the other hand, adults usually present with minimal to no symptoms and LCH is often diagnosed after removal of a solitary polyp [4]. They may present with perianal disease that can seem clinically indistinct from Crohn’s disease; therefore, a tissue biopsy may be necessary to make the correct diagnosis. The need for surgery in this small population of patients is uncommon but may be beneficial in the setting of worsening symptoms from local disease progression [4]. Our patient presented initially with perianal ulcerations and LCH was identified on biopsy of these lesions. He required a diverting colostomy for these non-healing wounds. His disease ultimately progressed to fibrous obliteration of the anus, and he developed pelvic pain and pressure from disease involvement and distention of the rectal stump. These symptoms were successfully alleviated after an abdominoperineal resection. This presentation, disease progression, and surgical treatment are unique for LCH and have not previously been reported in the literature.
References 1. Nanduri VR, Kelly K, Malone M, Milla P, Pritchard J (1999) Colon involvement in Langerhans' cell histiocytosis. J Pediatr Gastroenterol Nutr 29(4):462–466 2. Shima H, Takahashi T, Shimada H (2010) Protein-losing enteropathy caused by gastrointestinal tract-involved Langerhans cell histiocytosis. Pediatrics 125(2):e426–e432 3. Yadav SP, Kharya G, Mohan N, Sehgal A, Bhat S, Jain S et al (2010) Langerhans cell histiocytosis with digestive tract involvement. Pediatr Blood Cancer 55(4):748–753 4. Singhi AD, Montgomery EA (2011) Gastrointestinal tract langerhans cell histiocytosis: a clinicopathologic study of 12 patients. Am J Surg Pathol 35(2):305–310
LETTER TO THE EDITOR
Langerhans cell histiocytosis with anorectal involvement: a rare manifestation of adult disease Joshua Waters & Alyssa Fajardo & Bryan Holcomb & Virgilio George & Bruce Robb & Matthew Ziegler
Accepted: 9 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Editor: Langerhans’ cell histiocytosis (LCH) is a rare disorder of unknown etiology that is characterized by abnormal proliferation of Langerhans cells derived from the bone marrow [1, 2]. The Langerhans cell histiocytoses are defined by clonal proliferations of histiocytes, which are antigen-presenting dendritic cells. These cells are usually readily seen in the skin but can be identified in other organs, including bone, lungs, GI tract, liver, spleen, lymph nodes, and central nervous system. The affected cells have abundant and often vacuolated cytoplasm, with oval or indented nuclei. They are also characterized by the presence of Birbeck granules in the cytoplasm [1]. Colon involvement in LCH has been documented but has been historically thought to be uncommon, with incidence estimates ranging from 2 to 13 % [1]. Reported symptoms with colonic involvement have included diarrhea, rectal bleeding, failure to thrive, hypoalbuminemia, and protein-losing enteropathy [1]. Although GI tract involvement of LCH is rare, it is felt to be probably more common than previously recognized and is likely underdiagnosed because of the nonspecific presenting symptoms. Knowledge of this pathologic entity may help to ensure proper follow-up and further testing to assess for systemic disease [1]. Like Crohn’s disease, LCH involvement of the gastrointestinal tract can occur from the oral mucosa to the anal canal and perianal skin. It is unclear, however, whether perianal skin involvement is a manifestation of cutaneous or gastrointestinal disease [1]. Both Crohn’s disease and LCH can present with the finding of ulcerative lesions on colonoscopy, making pathology review of colon biopsies important for the J. Waters : A. Fajardo : B. Holcomb : V. George : B. Robb : M. Ziegler (*) Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA e-mail: [email protected]
diagnosis [2]. In addition, colon involvement of LCH can also manifest as colon polyps. Immunohistochemistry reveals Langerhans cells that are positive for CD1a and S100 protein [2]. Our colon and rectal surgery group recently took care of a 32-year-old male with a history of LCH who had initially presented over a decade ago with multiple perianal wounds and ulcerations, for which he underwent numerous excisions and biopsies. The biopsies revealed that cells of the histiocytic infiltrate were positive for CD1a and S100 protein. In 2004, he underwent a laparoscopic diverting colostomy for these nonhealing perianal ulcers. He was then lost to follow-up for many years but ultimately presented back with complaints of significant pain and pressure in his rectum that had been getting worse over the previous 4 months. He described the pain as dull and burning, and it increased in intensity with standing. He also stated that he no longer had an opening at his anus. On abdominal examination, he was noted to have a widely patent colostomy and no significant distention or tenderness during palpation. On perineal examination, however, no discrete anal opening was able to be identified, and the anal verge had been replaced by scar tissue. A CT scan of the abdomen and pelvis was performed and showed circumferential rectal wall thickening with an intraluminal stool ball but no adjacent inflammation. In addition, he was found to have mixed lytic and sclerotic lesions of the pelvic bones consistent with his history of Langerhans cell histiocytosis. Given his symptoms of increasing pelvic pressure and discomfort, he was ultimately taken to the operating room for a laparoscopic abdominoperineal resection. At surgery, he had a large impacted stool ball within the rectal lumen making mobilization of the rectum difficult. The traditional landmarks for the perineal portion of the dissection were distorted secondary to scarring and obliteration of the anus. The patient recovered well from surgery and his postoperative course was uneventful. Final pathology showed
Int J Colorectal Dis
benign rectal mucosa with surface denudation, muscularis propria smooth muscle hyperplasia, and obliteration of the anal canal. LCH that affects the colon is a rare manifestation of this pathologic process, and rectal disease is even less common. A 1999 review study identified 14 total patients reported in the literature with LCH of the colon, five of whom had rectal involvement [1]. Each of these rectal LCH patients was diagnosed in infancy and died at a young age. A 2010 review from India presented 39 total cases of GI tract involvement in LCH in the world literature, including two from their own institution [3]. Ten of these 39 patients (25.6 %) had rectal or anal biopsies that were positive for LCH. Of these ten patients with rectal involvement, nine died in infancy or early childhood. The tenth patient was noted to be in complete remission at 3month follow-up [3]. Johns Hopkins University published a review of their gastrointestinal tract LCH cases in 2011 which included ten adults and two children. This represented the largest series to date of adult GI tract LCH [4]. Eight of the ten adults presented with a solitary polyp and half of them were asymptomatic at presentation. Only one of the adults had an ulcerative lesion at the anus; the remainder had pathology confined to the stomach, small intestine, and colon [4]. Treatment for multisystem LCH has predominantly involved chemotherapy [2]. The LCH II trial results demonstrated that an effective first-line treatment for LCH includes vinblastine, prednisolone, and/or etoposide. 2-chlorodeoxyadenosine (2-CDA) may be used as second-line therapy. Patients with multi-system disease who fail conventional treatment may be candidates for stem cell transplantation [3]. In spite of these treatment options, 59 % of patients with gastrointestinal tract LCH involvement die within 18 months of diagnosis. These patients tend to have a high frequency of protein-losing enteropathy (77 %) which portends a poor prognosis [2]. Clearly, there is a significant difference in the presentation and outcome between adult and childhood LCH that involves the GI tract. Pediatric cases tend to be associated
with systemic disease and poor prognosis, and modern medical treatment for this population has been disappointing. Treatment of disseminated disease in children should not be delayed and any digestive symptoms in patients with LCH warrant an evaluation with colonoscopy. On the other hand, adults usually present with minimal to no symptoms and LCH is often diagnosed after removal of a solitary polyp [4]. They may present with perianal disease that can seem clinically indistinct from Crohn’s disease; therefore, a tissue biopsy may be necessary to make the correct diagnosis. The need for surgery in this small population of patients is uncommon but may be beneficial in the setting of worsening symptoms from local disease progression [4]. Our patient presented initially with perianal ulcerations and LCH was identified on biopsy of these lesions. He required a diverting colostomy for these non-healing wounds. His disease ultimately progressed to fibrous obliteration of the anus, and he developed pelvic pain and pressure from disease involvement and distention of the rectal stump. These symptoms were successfully alleviated after an abdominoperineal resection. This presentation, disease progression, and surgical treatment are unique for LCH and have not previously been reported in the literature.
References 1. Nanduri VR, Kelly K, Malone M, Milla P, Pritchard J (1999) Colon involvement in Langerhans' cell histiocytosis. J Pediatr Gastroenterol Nutr 29(4):462–466 2. Shima H, Takahashi T, Shimada H (2010) Protein-losing enteropathy caused by gastrointestinal tract-involved Langerhans cell histiocytosis. Pediatrics 125(2):e426–e432 3. Yadav SP, Kharya G, Mohan N, Sehgal A, Bhat S, Jain S et al (2010) Langerhans cell histiocytosis with digestive tract involvement. Pediatr Blood Cancer 55(4):748–753 4. Singhi AD, Montgomery EA (2011) Gastrointestinal tract langerhans cell histiocytosis: a clinicopathologic study of 12 patients. Am J Surg Pathol 35(2):305–310
