High Grade Dysplastic Rectal Adenoma in a Young Patient With Café‐Au‐Lait Spots: A Case Report

ABSTRACT

Colorectal cancer screening guidelines typically focus on familial history and age‐related risk factors, yet Café‐au‐lait macules could serve as early indicators for tailored surveillance protocols. This case underscores the importance of considering extracolonic manifestations in young patients presenting with colorectal symptoms. We present a case of a young patient with café‐au‐lait spots who was diagnosed with rectal tubulo‐villous dysplastic adenoma following rectal bleeding.

1. Introduction

Colorectal cancer (CRC) poses a substantial public health challenge due to its relatively high prevalence, yet early detection strategies offer significant potential for reducing mortality and morbidity [1]. Traditionally, early‐onset CRC has been linked to hereditary factors [2]. A wide range of extracolonic manifestations has been documented in the literature, which may serve as initial indicators of neoplastic colorectal syndromes in some cases [3]. Café‐au‐lait spots (CALS), typically associated with neurocutaneous syndromes like neurofibromatosis [4], have not conventionally been recognized as extracolonic manifestations of colorectal cancer. Nevertheless, isolated case reports have highlighted their presence in the context of hereditary nonpolyposis colorectal cancer, underscoring a potential genetic association [5].

In this article, we report a case of a young patient with notable CALS who was diagnosed with rectal tubulo‐villous dysplastic adenoma following presentation with rectorrhagia.

2. Case History

A 17‐year‐old Lebanese male presented to his primary care physician for painless rectal bleeding of 2 days' duration and altered bowel habits. For the past 2 months, the patient described having intermittent episodes of constipation and diarrhea. He also reported recent weight loss. Upon review, the patient's past medical and surgical history revealed no significant findings. He denied any smoking or alcohol consumption. No cases of CRC or other malignancies were reported in the patient's family history. The patient was then referred to a gastrointestinal physician for further investigation of rectal bleeding.

3. Investigations and Treatment

Abdominal examination revealed a soft, non‐tender, and non‐distended abdomen. However, dermatological inspection was notable for multiple café‐au‐lait spots. Three large well‐circumscribed, evenly pigmented patches of approximately 3 cm in diameter were found on his torso and near the buttock region (Figures 1 and 2); other small macules less than 10 mm in size were scattered along his gluteal crease (Figure 2). No other cutaneous signs suggesting neurofibromatosis were present on physical examination, and there was an absence of Lisch nodules and optic glioma; no previous work‐up of NF1 was done. Total colonoscopy was performed and identified a 1 cm sessile rectal polyp, around 10 cm from the anal verge (Figure 3). The polyp was subsequently resected through endoscopic mucosal resection (EMR) and sent for histopathological examination for further characterization.

FIGURE 1.

Scattered café‐au‐lait patches.

FIGURE 2.

Café‐au‐lait multiple scattered macules along the gluteal crease.

FIGURE 3.

A 1 cm rectal sessile polyp.

4. Conclusion and Results

Histopathologic examination of the biopsy specimen confirmed a tubulo‐villous adenoma with foci of high‐grade dysplasia. Thereafter, a full body and brain computed tomography (CT) scan was performed, which did not reveal any additional tumors that may be associated with the presence of CALS.

Genetic analysis performed later confirmed the diagnosis of Lynch syndrome in this patient with colorectal carcinoma and café‐au‐lait spots. Initially, immunohistochemistry (IHC) was performed on sections of the primary tumor to study the expression of the mismatch repair (MMR) proteins: MLH1, MSH2, MSH6, and PMS2. The results indicated the absence of both MSH2 and MSH6, thus indicating MMR deficiency. This was followed by testing for microsatellite instability, which tests the presence of MMR aberrations mostly seen in Lynch syndrome; this test revealed MSI‐high status. Next, germline genetic tests were conducted to identify key pathogenic variants in the MMR genes. A pathogenic alteration in the MSH2 gene was found, conclusively diagnosing Lynch syndrome. Genetic analysis for the family was advised but not pursued due to financial constraints.

The patient was referred to a surgeon and an oncologist, who recommended a partial colectomy followed by adjuvant chemotherapy. A follow‐up colonoscopy was scheduled for 6 months postoperatively.

5. Discussion

Café‐au‐lait spots are benign hyperpigmented skin lesions that are defined as macular, sharply demarcated, evenly pigmented patches [6]. These lesions are a common isolated dermatological finding in the general population, with most studies reporting between one and three CALS per person [7]. However, multiple CALS increase the possibility of an underlying neurocutaneous disease, the most common one being neurofibromatosis type I (NF1) [7]. They can also be present in other syndromes, including RASopathies like Legius syndrome, Watson syndrome, and Noonan syndrome with multiple lentigines, as well as McCune‐Albright syndrome, ring chromosome syndromes, and constitutional mismatch repair deficiency [6]. While several hereditary and nonhereditary gastrointestinal tract polyposis syndromes exhibit extraintestinal manifestations, including cutaneous findings such as CALS [8], they have not been considered an extracolonic manifestation of CRC [5]. However, a review of CRC case reports reveals occasional descriptions of CALS on physical exams [5]. Our patient, who was found to have a tubule‐villous adenoma, also had several CALS. While it did not yet progress to CRC, the histopathologic specimen showed a precancerous tubule‐villous adenoma with foci of high‐grade dysplasia. A full‐body and brain computed tomography (CT) scan conducted to exclude the presence of additional malignancies yielded negative results. The clinical picture of our patient did not meet the NIH diagnostic criteria for NF1, with the absence of Lisch nodules and optic glioma and other specific NF1 signs in addition to the negative family history of NF1 [6]. Despite having those dermatological findings, the patient was not previously investigated for them until he presented to our institution with complaints of abdominal pain, painless rectal bleeding, and altered bowel habits.

One study investigating CALS and early‐onset colorectal neoplasia identified a variant of Lynch syndrome characterized by oligo‐polyposis, early‐onset glioblastoma, and lymphoma. The study detailed the colonic and extracolonic phenotype in a family exhibiting both CALS and early‐onset colorectal neoplasia (adenomas and/or cancer) and reviewed an additional 23 families documented in literature. Among these 24 families, individuals were diagnosed with colorectal adenomas at a mean age of 15.7 years. Furthermore, 71.2% of the cohort (42 out of 59 individuals) were affected by CRC, diagnosed at an average age of 31.9 years. Notably, all families presented with CALS [5].

CALS were also found in patients with constitutional mismatch repair gene deficiency (CMMRD) [9]. Two cases of CMMRD with colorectal dysplastic polyps were described, and like our patient, the patients had CALS and the colonoscopy was done after they presented with rectal bleeding. Genetic investigations thereafter showed the presence of CMMRD [9, 10]. The absence of family history of cancer should not lessen the suspicion of CMMRD syndrome in some cases [11].

Taking into consideration all these aspects, it appears that there is an association between colorectal malignancy in the context of a genetic defect and the presence of CALS as an early sign of colorectal malignancy.

Taking into consideration all these aspects, it is evident that there is a significant correlation between colorectal malignancy in the context of a genetic defect and the presence of CALS as an early sign of colorectal malignancy. It has been noted by Lynch and de la Chapelle (2003) and Anaya et al. (2008) that colorectal cancer occurring before the age of 40 years is likely to have a familial inheritance, and hence testing for MMR gene variants like MLH1 and MSH2 is recommended. The early‐onset colorectal cancer in our young patient further confirms this association and should prompt further workup for hereditary syndromes like Lynch syndrome, which can manifest with CALS and colorectal malignancy at an unusually early age.

Back to our case, an earlier screening with colonoscopy would have detected polypoid lesions prior to their progression to premalignant in situ carcinoma. Genetic analysis performed later confirmed the diagnosis of Lynch syndrome in this patient with colorectal carcinoma and café‐au‐lait spots. Initially, immunohistochemistry (IHC) was performed on sections of the primary tumor to study the expression of the mismatch repair (MMR) proteins: MLH1, MSH2, MSH6, and PMS2. The results indicated the absence of both MSH2 and MSH6, thus indicating MMR deficiency. This was followed by testing for microsatellite instability, which tests the presence of MMR aberrations mostly seen in Lynch syndrome; this test revealed MSI‐high status. Next, germline genetic tests were conducted to identify key pathogenic variants in the MMR genes. A pathogenic alteration in the MSH2 gene was found, conclusively diagnosing Lynch syndrome. Genetic analysis for the family was advised but not pursued due to financial constraints.

Despite emerging research indicating a strong correlation between Hereditary Colorectal Cancer and café‐au‐lait spots, there are currently no established guidelines for colorectal cancer screening specifically tailored to individuals presenting with this dermatologic finding. Furthermore, given the early presentation of adenomas and the high incidence of colorectal cancer in individuals with CALS, it is recommended to have a higher degree of suspicion during workup and to consider earlier colonoscopy screening protocols in these patients. This approach aims to detect CRC before the development of any gastrointestinal symptoms, facilitating timely detection and therapeutic implications.

Author Contributions

Ali Hamdan: investigation, methodology, writing – original draft. Razan Abou Zeid: investigation, methodology, writing – original draft. Jana Khalil: investigation, methodology, writing – original draft. Karam Karam: data curation, investigation. Elias Fiani: supervision, writing – review and editing.

Consent

A signed written informed consent was obtained from the patient prior to writing the manuscript, attesting permission to publish the clinical history.

Conflicts of Interest

The authors declare no conflicts of interest.

Hamdan A., Zeid R. A., Khalil J., Karam K., and Fiani E., “High Grade Dysplastic Rectal Adenoma in a Young Patient With Café‐Au‐Lait Spots: A Case Report,” Clinical Case Reports 13, no. 10 (2025): e71045, 10.1002/ccr3.71045.

Data Availability Statement

Data will be made available upon request from authors.