Basaloid squamous cell carcinoma, metastasis in cervical lymph node.
- Cellular smear with predominant cohesive three-dimensional clusters and crowded tissue fragments of basaloid cells with few dispersed basaloid cells in background. Majority of cells are without definite keratinization.
- Occasional to few clusters of degenerating larger polygonal cells with hyperchromatic nuclei and a moderate amount of eosinophilic cytoplasm, suggesting squamoid differentiation.
- Crowded clusters show overlapping of nuclei with streaming pattern, but nuclear palisading is not seen
- Some tissue fragments are intimately mixed with hyalinised stromal material, with embedded ovoid to elongated and spindle cells. These cells have hyperchromatic nuclei with fine chromatin, similar to that of basaloid cells.
- Basaloid cells are small to medium in size with high N:C ratio, round to oval or angulated hyperchromatic nuclei with fine chromatin, absent or inconspicuous nucleoli and scant cytoplasm. Few basaloid cells are large in size with pleomorphic irregular nuclei and distinct small nucleoli.
- Some cellular clusters of basaloid cells with rosette-like structures or pseudo-glandular lumina with hyaline materials inside, mimicking adenoid cystic-like architecture
- Foci of necrosis, apoptotic bodies and frequent atypical mitoses are seen
- Some cells show the presence of nuclear molding; however, crushing is not seen.
Clinical Details: In present case, upper aerodigestive tract examination revealed a 3 × 2-cm ulcero-proliferative growth was present on the right side of nasopharynx. Present cytology taken from cervical lymphadenopathy.
Practical Points of Pathoclinics:
- Basaloid squamous carcinoma (BSCC) is an uncommon high-grade variant of primary squamous cell carcinoma of upper aerodigestive tract and other body sites. Cytologic features are not much described in the literature. Cytology smears of BSCC are moderately cellular, with predominant cohesive cell clusters, crowded irregular tissue fragments and isolated basaloid cells. Basaloid cells have relative larger nuclear size, inconspicuous or small distinct nucleoli, lack of crushing artifact, absence of nuclear molding and presence of single cell keratinization. However, single cell keratinization is only seen just above the 50% of all BSCC cases. Nuclear moulding and crushing may be seen in BSCC. Few dispersed populations of ovoid to spindle shaped cells with hyperchromatic nuclei are also embedded in hyalinized matrix tissue, like in present case. Few cells may show large pleomorphic nuclei like in present case. Necrosis, apoptosis, and mitotic activities are commonly present. Variable degree of adenoid cystic-like features or pseudo-glandular structures with hyalinized stromal material can be seen, like present case.
- Most of the cases of BSCC are misdiagnosed as small cell undifferentiated carcinoma or adenoid cystic carcinoma. Other differential diagnoses are metastatic basal cell carcinoma, basal cell adenocarcinoma, pleomorphic adenoma or carcinoma ex-pleomorphic adenoma and pilomatricoma. Significant stress should not be given on isolated single cell keratinization for the diagnosis of BSCC, as it can be seen in NUT midline carcinoma and poorly differentiated squamous cell carcinoma. The combination of small sized hyperchromatic basaloid cells with hyaline basement membrane–like material may led to the erroneous diagnosis of adenoid cystic carcinoma or pleomorphic adenoma or carcinoma ex-pleomorphic adenoma. Degenerated or metaplastic squamoid cells can be seen in pleomorphic adenoma or carcinoma ex-pleomorphic adenoma. Basaloid squamous cell carcinoma should be differentiated from these differentials because the treatment and prognosis are quite different.
- Small cell carcinoma: Most of the BSCC show a predominance of tightly cohesive tumor cell clusters and few dispersed cells, while small cell carcinoma contains mainly numerous dispersed single cell population and few loose aggregates of small cells with salt-pepper chromatin, nuclear molding and crushing artifacts. Squamous foci are very rare in small cell carcinoma. Extracellular hyaline material is also not seen in small cell carcinoma. In contrast to small cell carcinoma, only very few cases of BSCC show “salt-and-pepper” nuclei, crushing artifact and nuclear molding. Cells of small cell carcinoma are relatively small and show very little pleomorphism compared to BSCC. Nucleoli are very rarely seen in small cell carcinoma, but small distinct nucleoli are present in BSCC. Small cell carcinomas are positive for TTF-1, CD56, chromogranin and synaptophysin, while BSCC are typically CK5/6, p40 and p63 positive.
- Adenoid cystic carcinoma: Presence of neck node metastasis of adenoid cystic carcinoma is highly unusual. Presence of pseudoglandular/cribriform like structures with stromal hyalinized cores of BSCC may mimic adenoid cystic carcinoma. However, adenoid cystic carcinoma shows less cytologic pleomorphism, more angulated basaloid cells, few mitotic figures, less necrosis and very rare squamous differentiation. ACC characteristically shows solid homogenous rounded hyaline globules with surrounding uniform round basaloid cells. Adenoid cystic carcinomas show good expression of S-100 protein, CD117 and vimentin, in contrast negative or weak expression in BSCC. Solid sheet and nests of BSCC show diffuse nuclear staining with p63, in contrast to only peripheral myoepithelial cell staining in a cribriform pattern of ACC. Presence of MYB-NFIB fusion gene is characteristically present in ACC.
- Pleomorphic adenoma and Carcinoma ex-pleomorphic adenoma: Basaloid cells with metachromatic hyaline material in a myxoid background is seen in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma. Later shows more crowded clusters, overlapping nuclei, marked cellular atypia, mitoses, and necrosis. However, presence of single keratinised cells is very uncommon in both, though metaplastic squamous can be seen. Distinction of pleomorphic adenoma and Carcinoma ex-pleomorphic adenoma from BSCC, in absence of classic metachromatic hyaline matrix and myxoid substance is difficult.
- Adenosquamous carcinoma: Adenosquamous carcinoma has more prominent adenoid differentiation along with distinctive squamous component. Extracellular hyaline material is not seen in adenosquamous carcinoma. Presence of intracytoplasmic vacuoles favor the diagnosis of adenosquamous carcinoma.
- Basal Cell carcinoma (metastatic): Though metastatic basal cell carcinoma is very uncommon, cytomorphology of basal cell carcinoma is very close to BSCC. Smears of basal cell carcinoma show sharp well-defined tight aggregates of basal cells with crowding and overlapping, surrounded by stromal material, which represent retraction artifact, that is a feature of basal cell carcinoma on histology. Tight clusters have nuclear palisading at periphery. Here the basal cells are small, with ovoid hyperchromatic nuclei and scanty cyanophilic cytoplasm and indistinct cell borders. Nucleoli are indistinct. Mitoses can be seen. Cribriform like/adenoid cystic pattern is not seen.
- Basal Cell Adenocarcinoma: Cytologic features are very similar to basal cell adenoma, and exhibit bland nuclear features, rare mitosis and necrosis. Clusters of Basaloid cells in a tubular/glandular pattern may be seen, which may create confusion with pseudo-glandular structures of BSCC. Distinction between BSCC and basal cell adenocarcinoma is difficult on cytology alone. Basal cell adenocarcinoma has 2 types of cell population, large pale and small dark cells; the nuclei of these both are round to oval. However, significant cytologic atypia and mitotic activity have been reported on cytology of basal cell adenocarcinoma. Single cell keratinization, a feature of BSCC in few cases, is not seen in basal cell adenocarcinoma.
- NUT midline carcinoma: NUT midline carcinoma resembles a poorly differentiated squamous cell carcinoma, with aggressive behaviour. It has a characteristic translocation involving the NUT gene, with most common partner of BRD4. It is common in midline structures like sino-nasal tract. Cytology smears are highly cellular with prominent cell dispersal and loosely cohesive cells. Cells are small to medium in size with irregular nuclear border, distinct or prominent nucleoli, fine granular to vesicular nuclear chromatin and scanty cytoplasm. High mitotic activity, necrosis, karyorrhectic debris, and apoptosis are very common. Nuclear crushing may be seen. Squamous differentiation is a feature of NUT midline carcinoma; however, it is not necessary to be present in every case. Pseudo-glandular structure and pleomorphism are not a feature of NUT midline carcinoma. On immunohistochemistry, speckled nuclear positivity for NUT is characteristic feature.
- Pilomatricoma: Smears are usually cellular, comprising of loose aggregates of anucleate keratinized squamous cells (ghost cells) along with cohesive crowded clusters of basaloid cells. Here the basaloid cells are uniform and medium in size with hyperchromatic nuclei and scanty cytoplasm. Prominent component of basaloid cells may be misinterpreted as BSCC. Key feature is presence of ghost cells, which are not seen in BSCC. In addition, calcified debris, inflammatory cells, and foreign body giant cells are almost constant findings in Pilomatricoma.
Follow-up histology of above case shows features of Basaloid squamous carcinoma (BSCC):
- Tumour grows in a rounded nests and anastomosing broad trabeculae or ribbons, separated by thin lines of stroma creating a jigsaw puzzle–like pattern
- Focal peripheral palisading of nuclei are seen.
- Basaloid tumour cells have high nuclear to cytoplasmic ratios, open chromatin, distinct nucleoli and scant cytoplasm
- Abrupt transition between squamous and basaloid cells.
- Deposition of hyaline basement membrane like material, with pseudo-glandular or cribriform-like spaces and cord like pattern
- Comedo necrosis, frequent atypical mitoses and keratinization are readily identified
Joshi D, Shivkumar VB, Sharma SM, Gangane N. Cytomorphologic diagnosis of basaloid squamous cell carcinoma: a case report. Acta Cytol. 2009 Jan-Feb;53(1):89-92. doi: 10.1159/000325090. PMID: 19248560.