Acantholytic squamous cell carcinoma of larynx: An unusual cause of asphyxial death diagnosed on autopsy

INTRODUCTION

Laryngeal malignancies constitute 13% of all the head and neck region cancers.^[1] Principally, laryngeal malignancies are majorly of squamous cell lineage. Squamous cell carcinoma (SCC) is classified into two groups according to the pathological features: conventional (classic) type (95%) and variants of SCC (5%).^[2] SCC has quite a few variants, namely, conventional SCC (48–65%), basaloid carcinoma (4–10%), warty carcinoma (7–10%), papillary carcinoma (5–15%), verrucous carcinoma (3–8%), and mixed carcinomas.^[3] Each subtype has a distinct histomorphological feature. Acantholytic SCC (ASCC) represents a rare subset (2–4%) of SCC characterized by acantholysis of the tumor cells, creating pseudo lumina, and false appearance of glandular differentiation.^[4] Awareness of the diagnostic nuances of ASCC is indispensable for an accurate diagnosis as they exhibit deceptive morphological and immunohistochemical profile.

CASE REPORT

A 35-year-old young man was found unconscious on the railway station platform, following which he was taken to the hospital, where he was declared dead. On introspection with his family members, it was discerned that the individual had a recurring history of vocal cord polyps over the past year. He had experienced challenges encompassing both dysphagia and respiratory distress at night. He had undergone several microlaryngeal procedures, with the most recent polyp removal performed through carbon dioxide laser ablation, which unexpectedly was histopathologically diagnosed as a benign vocal cord nodule. A post mortem examination was sought to obtain insights and determine the precise cause of the abrupt demise. On autopsy, the pharynx, base of tongue, larynx, and both vocal cords were markedly congested. The lungs were turgescent and edematous. A large polypoidal mass occluding the airways was identified in the laryngeal lumen; thus, total laryngectomy along with partial glossectomy specimen was sent for histopathological examination. The entire specimen in-toto measured 15.5 × 8.5 × 5 cm. On opening, a large polypoidal, exophytic mass measuring 3 × 1 × 1.2 cm was seen in the glottic space [Figure 1]. The mucosa over the polyp and the surrounding mucosa appeared ulcerated. The mass was restricted to the midline; however, no extension into the right and left sides of the larynx was seen grossly. Sections studied from the polyp in the glottic region showed nests of malignant squamoid cells, displaying an infiltrative growth pattern. Individual cells showed increased nuclear-cytoplasmic ratio, hyperchromasia, irregular nuclear membrane, and dense eosinophilic cytoplasm. Within the tumor nests and islands, intercellular bridges, mitotic figures, and intracellular keratin along with keratin pearl formation were identified [Figure 2a]. In some foci, malignant squamous cells appeared dyscohesive and were seen scattered throughout the tumor substance [Figure 2b-f]. Periodic acid-Schiff stain negated the presence of any mucinous component. Right, left, and posteroinferior mucosal margins of the specimen showed only mild dysplasia; however, no frank tumor was seen in any of the margins or the adjacent structures. The tumor remained confined to the midline glottic space. On the basis of morphological features, a diagnosis of acantholytic variant of SCC was favored. A panel of immunohistochemical stains were put, to confirm this variant of SCC. To confirm the lineage of these malignant cells, cytokeratin 5/6 was applied, which showed diffuse cytoplasmic staining and confirmed them to be of squamous lineage [Figure 3a]. Epithelial-cadherin (E-cadherin) showed loss of expression in the malignant squamous cells, and vimentin positivity in the cells confirmed the epithelial mesenchymal transition (EMT) in the cells [Figure 3b and c]. Thus, a final diagnosis of SCC, acantholytic variant was proffered on postmortem examination.

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Figure 1:

Gross image showing an a polypoidal pedunculated mass present in the midline of the glottic region (autopsy specimen).

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Figure 2:

(a) Malignant tumor showing nests of squamoid cells, displaying an infiltrative growth pattern. Tumor nests and islands showing intercellular bridges and keratin pearl formation (HE ×40), (b and c) individual cells showing hyperchromasia, irregular nuclear membrane, and dense eosinophilic cytoplasm (HE ×40, ×100), and (d-f) malignant squamous cells appeared round to oval (acantholytic cells) and dyscohesive in nature, scattered throughout the tumor substance (HE ×100, ×200, ×400). HE: hematoxylin and eosin.

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Figure 3:

IHC- (a) CK5/6: Positive (×40) (Inset- high-power image [×200]), (b) Epithelial-cadherin: Negative (×40), (c) IHC: Vimentin positive (×100) (Inset- high-power image [×200]). IHC: Immunohistochemistry.

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DISCUSSION

ASCC, a subtype of SCC, has been known by various denominations such as, pseudoglandular squamous carcinoma, angiosarcoma-like SCC, and adenoid squamous carcinoma. ASCC was first coined by Lever in 1947 and described them by the proliferation of keratinocytes, which are variably-sized.^[5] These cells are dyscohesive in nature and, thus, form gland-like structures with these acantholytic cells. Although, head and neck region are the usual site, the possible occurrence at the mucosal sites of oral cavity, nasopharynx, tongue, and especially larynx has hardly been described in the literature.^[6,7] This variant of SCC shows non-solid components. This is typically characterized by free floating single or groups of acantholytic or dyskeratotic malignant epithelial cells. Thereby, forming pseudoglandular or pseudovascular structures. The tumor cells of ASCC, contrary to conventional SCC, shows a significant amount of pleomorphism. Thus, appearing extremely bizarre as typically seen in poorly differentiated malignant tumors. Features such as irregular nuclear membrane, hyperchromasia, and prominent nucleoli are quite often seen in ASCC. Brisk mitosis, along with atypical forms is frequently seen. The cells show variable amount or dense eosinophilic cytoplasm. There is an absence of epithelial mucin production (so as to differentiate from adenosquamous variant of SCC).

These cells of ASCC lose the quintessential attributes of conventional SCC, simulating other epithelial or mesenchymal malignancies. The cells lose intercellular junctions and cellular polarity, acquire mesenchymal properties, and gain increased motility, leading to EMT. E-cadherin is a cell adhesion molecule,and a tumor suppressor protein plays a significant role in EMT. It acts as a morphogenetic controller by altering the tissue maturation and tumor differentiation. In normal conditions, E-cadherin is present in nearly all developed epithelial cells of human tissue and many solid malignant epithelial tumors; however, its expression is typically decreased in a few tumors like lobular carcinoma of the breast. The tumor cells of ASCC show significant down regulation of E-cadherin along with an up regulation of Vimentin (mesenchymal marker), Claudin-1 (tight junction protein), bringing about EMT, and invasion of tumor cells.^[8] Griffin et al. noted that E-cadherin expression was significantly reduced in ASCC, compared with SCC.^[9]

Clinically, the head and certain facial locations (lips) are favored by ASCC. Conversely, distal sites on both the upper and lower limbs are favored by conventional SCC. Cunha et al.,^[10] in their study, compared the tumor behavior of conventional SCC with ASCC,and found a higher tumor grade, deeper infiltration, and vascular invasion in ASCC than in typical SCCs. Furthermore, they observed a higher incidence of regional, lymph nodal metastasis, and mortality due to the aggressive behavior of ASCC.^[10] Similarly, Bayer-Garner et al. found that the reduced expression of E-cadherin was associated with a poor prognosis in ASCC cases.^[11] Factors such as tracheal mucosal infiltration and poor-differentiation of tumor are considered as unfavorable prognostic and predictive factors. This tumor variant being rare in itself, has hardly been described at larynx, thus leading to a limitation on information of pathological, immunohistochemical findings, and prognosis [Table 1].

CONCLUSIONS

In conclusion, the report emphasizes that ASCC is an uncommon subtype of SCC, rarely observed in mucosal locations, particularly within the larynx. Given the tumor’s inherently aggressive nature, resulting in a fatal outcome, occurrences of this nature are exceedingly rare, underscoring the significance of this documentation.