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Ann Coloproctol > Volume 40(Suppl 1); 2024 > Article
Sandoval, Lara-Endara, Rodríguez-Suárez, Garzón, Redrobán, and Montalvo: Melanocytic nevus of the anal canal and granular cell tumor of the cecum: a case report and literature review of 2 coincidentally co-occurring neurocristopathies

Abstract

Granular cell tumors are predominantly benign soft tissue tumors originating from Schwann cells, whereas melanocytic nevi are benign proliferations of melanocytes. We present the case of a patient with the presence of both entities located in the cecum and anal canal, respectively, constituting an extremely rare coincidental finding. A 43-year-old woman was evaluated by colonoscopy for iron-deficiency microcytic anemia that had lasted for 1 year. Colonoscopy demonstrated a macular lesion of 0.3 cm with a melanocytic appearance in the anal canal; at the cecum level, a subepithelial, yellowish, and partially mobile firm nodular lesion measuring 1.3 cm was observed. A histopathological study showed a melanocytic nevus in the anal canal and a granular cell tumor in the cecum. This is the first reported case of a patient with the extremely rare coincidental-incidental finding of these 2 entities at the same time.

INTRODUCTION

Granular cell tumors (GCTs) account for 0.5% of soft tissue tumors; they are derived from Schwann cells, and their most frequent locations are the oral cavity, skin, and subcutaneous tissues [1, 2]. These tumors frequently affect women from their 4th to 6th decade of age; most of these tumors are isolated and tend to be benign. Two systematic reviews of GCTs determined that the prevalence of these tumors in the gastrointestinal tract is between 5% and 30%, and 20% of all GCTs found in the gastrointestinal tract are in the colon [3, 4]. Melanocytic nevi (MNs) are benign proliferations of melanocytes that tend to be localized in sites that receive the most sun exposure. When these lesions occur in unusual anatomic sites or have uncommon histopathologic features, they are described as “MNs of special sites”; however, MNs in the anal canal are not included in this classification due to their extreme rarity. Until 2017, there have been only 10 reported cases of this lesion [5]. We report the first case of a patient with GCT of the cecum and MN in the anal canal detected at the same time; the only relationship of these conditions with each other was their embryonic cellular origin in the neuroectoderm.

CASE REPORT

A 43-year-old woman with no relevant pathological history other than rheumatic fever presented for a consultation for fatigue, general discomfort, palpitations, and dizziness of 1 year’s duration. Her menstrual cycles were regular, but with heavy bleeding of 7 to 8 days per cycle. On a physical abdominal examination, a hard mass was palpated in the hypogastrium, and the rest of the physical examination was normal. Blood biometry reported microcytic iron-deficiency anemia; therefore, it was decided to investigate the cause of bleeding in this woman of childbearing age. Simple and contrast-enhanced computed tomography of the abdomen and pelvis revealed an enlarged uterus due to multiple solid masses suggestive of myomas, the largest of which was 7 cm in diameter, occupying the uterine fundus. In addition, an endoscopy and colonoscopy reported a macular lesion of about 0.3 cm, with melanocytic appearance, without erosions in the anal canal (Fig. 1A). At the cecum level, a firm nodular lesion, approximately 1.3 cm in diameter, subepithelial, yellowish and partially mobile, was observed (Fig. 1B). Due to the patient’s clinical condition, the size of her uterus, myomas, and colonoscopy findings, the multidisciplinary team decided to perform a hysterectomy, together with exeresis of the cecum tumor and the melanocytic lesion in the anal canal. A histopathological study showed 2 transmural leiomyomas, an MN in the anal canal of 0.2 cm (Fig. 2C), and a GCT in the cecum of 1.3 cm in diameter with free resection edges (Fig. 2A). Immunohistochemistry studies of the GCT reported positivity for S100 (insert in Fig. 2B) and negativity for DOG-1 (not shown). Both the GCT and the MN showed positivity for SOX-10 (Fig. 2B and insert in Fig. 2D). Six years after surgery, the patient is asymptomatic, and her iron-deficiency anemia has been completely corrected.

Ethics statement

This study was conducted in accordance with the Ethics Committee of Hospital Metropolitano (Quito, Ecuador). The study was approved by the Institutional Review Board of Comité de Ética de Investigación en Seres Humanos del Hospital General San Francisco (No. CEISH-HGSF-2022-039). The patient agreed that the stored material was enclosed, and her clinical data were anonymously used. Written informed consent for publication of the research details and clinical images was obtained from the patient.

DISCUSSION

Schwann cells and melanocytes result from the coordinated migration and differentiation of neural crest cells (NCCs) during embryonic formation. Genetic and epigenetic defects are responsible for disrupting the transcription factors that regulate these cells, causing syndromic diseases and tumors related to NCCs, known as neurocristopathies [6]. Despite sharing embryonic origin and precursor cells, there are no reports of tumors or syndromes involving GCTs and MNs. The SOX-10 transcription factor plays an important role in neural crest development and cell fate differentiation. It serves as a marker for migratory multipotent neural crest progenitors and their derivatives; hence, mutations in this gene have been described in multiple neurocristopathies, including those involving melanocytes and aberrant Schwann cell development [7]. We believe that the banality of MNs leads to a lack of attention to the synchronous presentation of these 2 entities. However, the rarity of the concomitant incidence of GCT and the exceptional location of the MN make our case unique.
The colon is the second most commonly affected organ of the gastrointestinal tract by GCTs after the esophagus. Most GCTs occur in the cecum and ascending colon. Often, these tumors are found by chance, as in our patient; however, some cases may involve rectal bleeding, abdominal pain, and stool changes [4, 8]. Macroscopically, these tumors tend to be submucosal and yellowish, and their diameter is less than 2 cm. Due to the macroscopic similarity to polyps and other tumors that can be found simultaneously in the patient, the diagnosis remains histopathological. The most common finding is clusters of spindle cells or epithelioid cells with small nuclei. The granular appearance is due to the accumulation of phagolysosomes in the eosinophilic cytoplasm. The immunohistochemical study demonstrated Schwann cells as the cellular origin, with positivity for S100, CD68, and neuro-specific enolase. Unlike the other organs, in which GCTs can occur, the gastrointestinal tract is characterized by nuclear atypia [2, 4]. Although the risk of malignancy of these tumors is less than 2.5%, their potential to metastasize must be considered. Therefore, the approach should be the complete removal of the tumor with free resection margins to reduce the risk of recurrence and prevent its malignant transformation [2]. Currently, the removal of colon GCT can be performed surgically or endoscopically; in our patient, we chose the surgical approach due to the need to perform a hysterectomy for her myomas.
Acquired MNs are clonal proliferation of melanocytes due to activation of oncogenes through mutations in BRAF or NRAS that do not show evidence of dysplasia or atypia. They can be found in any skin compartment and, in extremely unusual cases, in mucous membranes. They frequently occur in areas with chronic exposure to ultraviolet light and undoubtedly have an important genetic component [9]. MNs occurring in exceptional areas (ear, acral, genital, breast, scalp, flexural sites, or umbilical) or having atypical microscopic findings are described as special site nevi [10]. MNs in the canal should be including in this group; however, their occurrence is so unusual that they have been described in only a few case reports and case series. The presence of melanocytes along the anal canal was described by Clemmensen and Fenger [11] in 1991; in theory, it should not be uncommon to find MNs at this anatomical site in light of the similarity of the epithelium and cellularity of the rest of the body epidermis. Aljufairi and Alhilli [5] argued that the reasons why there are few cases of MNs in the anal canal are the maturation and involution of melanocytes of the anal canal, which may resemble what happens with MNs in the rest of the body, and the low degree of detection by clinicians and pathologists. Most MNs of the anal canal reported were found incidentally because they co-occurred with other pathologies (hemorrhoids, anal fissures, and melanoma of the anal canal). In our case, the patient did not present any other associated lesion; instead, it was an incidental finding visualized on colonoscopy, and there are no previous reports of this type of finding in the literature. The melanocytic lesion in our patient might have taken one of the following paths: involution, stability as a benign lesion without morphological changes, or transformation into a malignant lesion.
The simultaneous finding of 2 neoplasms in the same patient should not be considered as a simple coincidence without first exploring similar oncogenic pathways and possible related syndromes. In the present case, the only relationship between the GCT in the cecum and the MN in the anal canal was their embryonic origin and progenitor cells. Despite the benign behavior of both neoplasms, their removal with free surgical edges is essential to prevent recurrence and to avoid the risk of malignancy. More reports on MNs in the anal canal are needed to assess with greater certainty how many cases occur in patients without other associated diseases of the anal canal. It is also necessary to emphasize the importance of evaluating anal canal pathologies with histopathological studies to look for melanocytic lesions that may be overlooked and could produce an unnecessary risk of malignancy. It should be taken into account that the prevalence of this entity may be higher than what is estimated.

Notes

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

FUNDING

None.

AUTHOR CONTRIBUTIONS

Conceptualization: all authors. Investigation: VS, JLE. Resources: NM, LR, JRS, WAG. Supervision: NM. Visualization: LR. Writing–original draft: VS, JLE. Writing–review & editing: all authors.

All authors have read and approved the final manuscript.

Fig. 1.
Colonoscopy demonstrated the following findings. (A) A macular lesion of about 0.3 cm, with melanocytic appearance, without erosions in the anal canal. (B) At the cecum level, a firm nodular lesion, approximately 1.3 cm in diameter, subepithelial, yellowish, and partially mobile.
ac-2022-00444-0063f1.jpg
Fig. 2.
Microscopic images. (A, B) Granular cell tumor of the cecum. (A) Submucosal proliferation of nests or ribbons of cells separated by thin collagenous bands (hematoxylin-eosin, ×10). The cells are round and polygonal to slightly spindle-shaped, with abundant eosinophilic cytoplasm, and mild to moderate nuclei atypia (inset image, ×40). (B) SOX-10 nuclear expression is diffuse in tumor cells (×10). Diffuse cytoplasmic and nuclear S100 expression in tumor cells (inset image, ×20). (C, D) Melanocytic nevus of the anal mucosa. (C) Melanocytic nests are uniform in size and have an abundant pigmented cytoplasm (hematoxylin-eosin, ×10). A lesion sample shows smaller cells with less pigment and less atypia (inset image, ×40). (D) SOX-10 nuclear expression is diffuse in nevus cells (×10; inset image, ×40).
ac-2022-00444-0063f2.jpg

REFERENCES

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