HPV-Negative Basaloid Squamous Cell Carcinoma of the Rectum: An Exceptionally Rare Entity

ABSTRACT

Basaloid squamous cell carcinoma (BSCC) of the rectum is an exceptionally rare malignancy, distinct from other more common gastrointestinal cancers. Although human papillomavirus infection is strongly associated with squamous cell carcinomas at other anogenital sites, its role in rectal BSCC remains unclear. We report a 66-year-old woman who presented with fatigue and intermittent hematochezia. Colonoscopy revealed a distal rectal mass, and biopsy confirmed poorly differentiated BSCC. Immunohistochemistry was negative for human papillomavirus. Molecular profiling demonstrated high tumor mutational burden and elevated PD-L1 expression. This case underscores the extreme rarity of rectal BSCC and the diagnostic and therapeutic challenges it poses.

INTRODUCTION

Rectal basaloid squamous cell carcinoma (BSCC) is a rare subtype of squamous cell carcinoma with a nonspecific clinical presentation, often leading to delayed diagnosis. In the literature, 10 cases have been reported in which the rectum was involved, with only 2 cases confined solely to the rectum, rendering it nearly unprecedented and insufficiently characterized compared to other rectal cancer.^1,2

BSCC most commonly arises in the head and neck.^3,4 It can occasionally involve gastrointestinal tract sites such as the esophagus, colon, and anorectal area. However, involvement of the rectal area is unique.^5–7

BSCC is more common in elderly people. Although BSCC in the anal canal primarily affects women and is strongly connected to high-risk human papillomavirus (HPV) infection, esophageal BSCC is more common in men and is frequently associated with alcohol and tobacco use and with a subgroup caused by HPV.^8,9 Rectal BSCC is scarcely described, and risk factors are not fully understood.

We report the case of a 66-year-old woman without significant medical history who presented with severe anemia due to worsening lower gastrointestinal bleeding. Initial evaluation demonstrated a large, fungating, nonobstructive mass in the distal rectum. Histopathological analysis of biopsy revealed poorly differentiated squamous cell carcinoma with basaloid features.

CASE REPORT

A 66-year-old woman with no significant medical history presented with fatigue and intermittent hematochezia for the past 8 months, which had worsened over the preceding 2 weeks, presenting as blood-streaked stool.

She denied fever, chills, weight loss, night sweats, nausea, vomiting, diarrhea, inflammatory bowel disease, or a family history of colon cancer. The patient had not had recent follow-up or colon cancer screening.

On admission, vital signs showed blood pressure of 95/60 mm Hg but were otherwise unremarkable. Physical examination revealed pale skin and conjunctiva, with a nontender abdomen. Direct rectal examination showed light brown stool in the rectal vault with a palpable nodular mass and a normal rectal tone. Laboratory results were significant for a hemoglobin of 3.9 g/dL (without a previous baseline) and a mean corpuscular volume of 71.1 fL. The carcinoembryonic antigen marker was negative. Four units of packed red blood cells were given. Computed tomography of the abdomen and pelvis demonstrated asymmetric rectal wall thickening, without metastatic disease. Magnetic resonance imaging of the abdomen and pelvis revealed circumferential rectal thickening and tumor extension beyond the muscularis propria into the mesorectal fat, suggesting cancer staging of T3 (Figures 1 and 2).

Figure 1.

Axial pelvic magnetic resonance imaging demonstrating an asymmetric rectal wall mass extending beyond the muscularis propria, suggestive of a T3 tumor.

Figure 2.

Sagittal pelvic magnetic resonance imaging demonstrating a rectal mass with extension beyond the muscularis propria, consistent with a T3 tumor.

Esophagogastroduodenoscopy demonstrated a slightly irregular Z-line, while the stomach and duodenum appeared unremarkable. Colonoscopy revealed a large, fungating, nonobstructing mass in the distal rectum without evidence of bleeding, involving half of the lumen (Figure 3).

Figure 3.

Endoscopic image showing a 5-cm fungating, nonobstructing rectal mass without evidence of active bleeding.

Biopsy of the rectal mass revealed an invasive, poorly differentiated squamous cell carcinoma with basaloid features (Figure 4). The tumor showed malignant basaloid cells invading the underlying stroma. Immunohistochemical staining demonstrated strong p63 positivity, whereas p16 showed only patchy moderate staining. Subsequent in situ hybridization for HPV was negative, suggesting a non–HPV-related tumor. Tumor cells were negative for synaptophysin, CK7, CK20, and CDX2, supporting the diagnosis of BSCC of the rectum.

Figure 4.

Rectal biopsy showing basaloid tumor invading underlying stroma (hematoxylin and eosin, ×40).

Molecular profiling of the rectal tumor revealed multiple genetic alterations, high tumor mutation burden, elevated programmed death-ligand 1 (PD-L1) expression, and absence of HPV, Epstein-Barr virus, or microsatellite instability.

The patient was managed by a multidisciplinary team including oncology, radiation, and colorectal surgery, treated with 5-fluorouracil, mitomycin C, and radiation therapy, with planned surgical evaluation for incomplete response. However, during therapy, she was readmitted with hypotension and necrotizing fasciitis and died despite aggressive management.

DISCUSSION

BSCC is a highly uncommon subtype of squamous cell carcinoma that can involve the gastrointestinal tract. Although BSCC has been reported in the esophagus, colon, and anorectal region, its occurrence is uncommon at all of these sites, and involvement of the rectum is particularly exceptional, only 2 cases of primary BSCC occurring exclusively in the rectum have been documented.^1,2 In the anal region, Patil et al analyzed 15 cases of BSCC, whereas Graham et al reviewed 27 cases.^6,7 In the esophagus, Baba et al identified 22 BSCC cases among 502 esophageal cancers (4.4%),¹⁰ highlighting the scarcity of this tumor across gastrointestinal sites and the unique nature of rectal BSCC.

HPV is a well-recognized risk factor in the development of squamous cell carcinoma, particularly BSCC in various anatomical locations, and a primary etiology of anal BSCC.¹¹ Romanczyk et al described a case of rectal BSCC, and HPV was positive on molecular analysis.¹ In contrast, in our case, HPV was evaluated using p16 immunohistochemistry, which showed patchy staining inconsistent with HPV and was confirmed negative by in situ hybridization. HPV polymerase chain reaction testing was not performed, which represents a limitation of this report. To our knowledge, our case represents the first HPV-unrelated BSCC of the rectum. Given the limited number of reported cases, the association between HPV and rectal BSCC has not been established.

The clinical presentation of BSCC can be nonspecific and variable. In the case described by Kacerovska et al, the patient presented with a 1-month history of anal discomfort and bleeding, whereas our patient reported progressively worsening fatigue and hematochezia for 8 months.¹²

BSCC is more prevalent in older adults. In a series of 18 esophageal BSCC cases, Cho et al found that the median age was 57 years.¹³ In contrast, Graham et al's dataset of 27 anal BSCC cases revealed a median age of 60 years.⁷ The patient in the case reported by Romańczyk et al was a 47-year-old patient, whereas Machairas et al described a 33-year-old patient, whereas our patient was 66 years old, emphasizing that due to the limited number of reported cases, the typical age group for BSCC confined to the rectum cannot be clearly established.^1,2

The case contributes to the limited literature on rectal BSCC, highlighting the rarity of this malignancy, and represents the first documented instance of HPV-negative BSCC of the rectum. Additional rectal BSCC reports are required to better characterize this subtype of malignancy.

DISCLOSURES

Author contributions: I. Grossmann: Conceptualization of the case report, data collection, drafting of the manuscript, and final approval of the submitted version. H. Sanekommu: Gastroenterology consultation, interpretation of endoscopic findings, and manuscript review. S. Ahsan: Literature review, assistance with data interpretation, and manuscript editing. N. Campbell: Manuscript review and critical editing. V. Taneja: Gastroenterology consultation, interpretation of clinical and endoscopic findings, and manuscript review. L. Peng: Gastroenterology oversight, critical revisions related to clinical interpretation, and final manuscript approval. A. Chinnici: Supervision, manuscript review, and final approval. S. Sen: Supervision, manuscript review, and final approval. M. Hossain: Supervision, manuscript review, and final approval. M. Hossain will serve as the article guarantor and accepts full responsibility for the integrity of the work, including the conduct of the study, the accuracy of the data, and the final manuscript content.

Financial disclosure: The authors declare that they have no actual or potential conflicts of interest related to this manuscript.

Informed consent was obtained for this case report.

ABBREVIATIONS:

BSCC

Basaloid squamous cell carcinoma

HPV

Human papillomavirus

PD-L1

Programmed death-ligand 1