NUT Carcinoma of the Lacrimal Apparatus Presenting as a Rapidly Enlarging Medial Canthal Mass: A Case Report

Abstract

Introduction

NUT carcinoma (NC) is a rare, aggressive squamous-lineage malignancy characterized by NUTM1 gene rearrangement and distinctive nuclear NUT expression by immunohistochemistry. Ocular adnexal involvement is exceptional.

Patient presentation

A 26-year-old woman presented with redness, pruritus, and a large nasal canthal mass obstructing vision in the left eye. Examination showed a 4 × 3 cm lacrimal mass extending into the extraconal orbit with extraocular muscle compression. Histology showed nests of small round blue cells with crush artifact and abrupt keratinization. Immunohistochemistry demonstrated diffuse pan-keratin, p63, p40, and speckled nuclear NUTM1 positivity; CD99 and NKX2.2 were negative—confirming NC.

Conclusion

Lacrimal sac/gland NC should be considered in rapidly enlarging medial canthal masses in young patients. Prompt biopsy with IMMUNOHISTOCHEMISTRY for NUT and early multidisciplinary management are critical.

Introduction

NUT carcinoma (NC) is a distinct, genetically defined poorly differentiated carcinoma characterized by rearrangement of the NUTM1 gene and typically shows variable squamous differentiation with expression of squamous markers. Often, this gene is fused to members of the bromodomain and extraterminal domain family such as BRD4. Punctate nuclear staining for NUT on immunohistochemistry (IHC) is pathognomonic. ¹ Although historically described in the midline head and neck and mediastinum of adolescents and young adults, the anatomic spectrum of NC now includes diverse sites. ²

According to a retrospective study by Lee et al in China, the prevalence of NC is about 1.1% in head and neck carcinomas. ³ However, it is very difficult to pinpoint the true prevalence of this condition due to diagnostic challenges and lack of standardized data collection methods. The median survival in this condition is 6 to 9 months only, highlighting the aggressiveness of the tumor.

Involvement of the ocular adnexa is exceptionally rare, and tumors arising from the lacrimal apparatus may be overlooked because their initial manifestations resemble far more common inflammatory or benign lacrimal disorders. ⁴

We report a lacrimal apparatus NC in a 26-year-old woman initially evaluated for “infective” lacrimal disease, highlighting the diagnostic pathway, surgical management, and early oncologic planning, and we discuss the implications for timely multidisciplinary care in this rare yet lethal entity.

Patient Information

A 26-year-old female patient presented with painful redness, pruritus, and a rapidly enlarging swelling at the left medial canthus that had begun to encroach on the visual axis and intermittently blurred vision. She reported no history of fever, trauma, prior ocular surgery, or similar episodes. There was no personal or family history of malignancy or autoimmune disease, and no relevant occupational or environmental exposures were elicited. Past medical, surgical, and psychosocial histories were otherwise unremarkable, with no regular medications or substance use and no recent systemic symptoms such as weight loss or night sweats. She first sought care with ophthalmology, where clinical examination raised concern for a lacrimal apparatus mass. An incisional biopsy was performed, and tissue was submitted to the pathology laboratory for histopathologic evaluation and IHC, which guided subsequent referral for definitive oncologic management. Figure 1 shows the clinical photograph with left medial canthal swelling causing tense, violaceous bulge with partial mechanical ptosis and conjunctival injection.

Figure 1.

Clinical photograph showing left medial canthal swelling causing tense, violaceous bulge with partial mechanical ptosis and conjunctival injection.

Clinical Examination

On presentation, the patient had a tender, erythematous, fluctuant swelling over the left medial canthus consistent with a lacrimal sac abscess, with features of acute dacryocystitic retention despite a clinically patent nasolacrimal duct. Conjunctival chemosis and mild mechanical ptosis encroaching on the visual axis were noted, with extraocular movements limited by mass effect; visual complaints included intermittent blurring. Deep palpation suggested an additional, well-defined, loculated soft-tissue fullness inferotemporally in the left orbit. The overlying skin showed no ulceration or discharge, and there was no palpable preauricular or cervical lymphadenopathy. Bedside sinonasal assessment revealed no clinical evidence of contiguous paranasal sinus involvement. Initial imaging correlation described a 2.7 × 1.8 × 2.4 cm lobulated lesion centered in the left lacrimal sac extending into the nasolacrimal duct and extraconal orbit with extraocular muscle compression, without radiologic sinus extension, an appearance initially favored to be infective/inflammatory. Figure 2 shows the gross specimen tan-white in color, firm mass measuring ∼4 × 3 cm from the lacrimal apparatus. The cut surface was solid and heterogeneous with focal whorled pale areas.

Figure 2.

Gross specimen showing tan-white, firm mass measuring ∼4 × 3 cm from the lacrimal apparatus. The cut surface is solid and heterogeneous with focal whorled pale areas.

Diagnostic Assessment

Given the lesion's persistence and progressive course, an incisional biopsy was performed. Microscopic examination of the tissue revealed a malignant neoplasm composed of nests of small round blue cells exhibiting prominent crush artifact. A striking histologic feature was the presence of foci of abrupt keratinization within many of the tumor nests. These findings have been identified in Figure 3, Figure 4 and Figure 5. Immunohistochemical staining confirmed diffuse expression of broad epithelial markers including pan-keratin, as well as squamous lineage markers p63 and p40. Critically, there was characteristic punctate (“speckled”) nuclear positivity for NUTM1 protein. Markers such as CD99 and NKX2.2, which are typically expressed in Ewing sarcoma/primitive neuroectodermal tumor (PNET), were negative.

Figure 3.

Histology, low power; poorly differentiated carcinoma in solid nests with necrosis and abrupt keratinization.

Figure 4.

Histology, high power; sheets of small round blue cells with crush artifact and scattered dyskeratotic foci.

Figure 5.

Histology, high power; tumor cells with high N:C ratio and focal squamoid differentiation; background necrotic debris.

These findings established the diagnosis of NC of the lacrimal apparatus. The differential diagnosis initially included infectious dacryocystitis/abscess, poorly differentiated squamous cell carcinoma, sinonasal undifferentiated carcinoma, Ewing sarcoma/PNET, and lymphoma. However, the combination of abrupt keratinization, squamous marker positivity, diagnostic nuclear NUT expression, and the absence of Ewing markers definitively excluded these alternatives.

Discussion

NUT carcinoma is defined by NUTM1 rearrangement, commonly BRD4::NUTM1, with pathognomonic punctate (“speckled”) nuclear NUT staining on IMMUNOHISTOCHEMISTRY. ⁵ It may present as an undifferentiated or poorly differentiated carcinoma with abrupt keratinization. Abrupt keratinization within an otherwise poorly differentiated tumor has been increasingly recognized as a subtle but important morphologic clue to NC, even when classical squamous differentiation is limited. Awareness of this feature is particularly valuable in small biopsies, where morphologic heterogeneity and focal immunoreactivity may otherwise lead to misclassification. ⁶ In the orbit/lacrimal apparatus, it may mimic dacryocystitis or lacrimal sac tumors such as poorly differentiated SCC, lymphoma, or Ewing sarcoma, making the negative CD99/NKX2.2 and the strong p63/p40/pan-keratin plus NUT staining pattern crucial for distinction in small biopsies.

Recent sinonasal series have shown that NC frequently presents as a poorly differentiated small round cell tumor with orbital extension, where diffuse p63/p40 and nuclear NUT positivity with absence of CD99 and NKX2.2 are critical for distinguishing it from Ewing sarcoma, SNUC, and lymphoma. These findings mirror the immunoprofile in the present lesion and underscore the importance of routine NUT testing in undifferentiated sinonasal–lacrimal tumors. ⁷

Although p63 and p40 are commonly coexpressed in NC, discordant staining can occur; therefore, interpretation should rely on the overall morphologic context and confirmatory nuclear NUT expression (and/or molecular evidence when needed).

Similar diagnostic challenges have been described in orbital and perilacrimal NC, where initial symptoms such as epiphora or medial canthal swelling closely simulated inflammatory lacrimal disease, resulting in delayed recognition of an aggressive malignancy. ⁴ Reports of orbit-involved NC emphasize that rapid progression despite conservative management should prompt early biopsy and molecular confirmation.

Conclusion

In young patients with a rapidly enlarging medial canthal mass, NC should be included in the differential diagnosis. Given the marked aggressiveness of this entity and the risk of misclassification as other poorly differentiated malignancies, NUT IHC should be routinely performed in poorly differentiated carcinomas of the head and neck to enable timely diagnosis and triage. Early biopsy with an appropriate IHC panel and prompt multidisciplinary tumor board–guided management are critical.