Combined small-cell carcinoma of the lung with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type

Abstract

The combined variant of small-cell lung carcinoma (SCLC) refers to the variable admixture of small cell and non-small cell carcinoma, whereas the association with sarcoma or sarcoma-like elements is exceedingly rare. A 76-year-old Caucasian man underwent right upper lobectomy with regional lymphadenectomy because of a symptomatic 7 cm-sized tumor mass. Formalin fixed-paraffin embedded material was used to highlight several differentiation cell lineages by means of immunohistochemistry, electron microscopy, and mutational assay. The tumor was discovered as being IIB stage (pT2b pN1(1/51) pM0) and featured biphasic appearance with close intermingling of SCLC (40%) and collagen-rich spindle cell sarcoma (60%). Epithelial (cytokeratins, TTF-1), neural (neurofilaments, GFAP), endocrine (chromogranin, synaptophysin, CD56), and skeletal muscle (desmin, sarcomeric actin, myogenin) markers were variably co-expressed by SCLC elements, whereas mesenchymal (vimentin), smooth muscle (actin, myosin, H-caldesmon, calponin), fibroblastic (CD10), and, more focally, skeletal muscle (desmin, sarcomeric actin and myogenin) markers were highlighted in the spindle cell sarcoma elements. TP53 codon V274F mutation in exon 8 was shared by either cell component. After undergoing adjuvant chemotherapy, the patient is currently alive and well at the 40-month follow-up. To the best of our knowledge, this is the first report of combined SCLC with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type, somewhere at the level of the same individual tumor cells. This tumor had probably derived for clonal evolution of a p53-mutated common ancestor lesion.

Frequent Mutations in EGFR, KRAS and TP53 Genes in Human Lung Cancer Tumors Detected by Ion Torrent DNA Sequencing

“…Additionally, SCLCs are typically much more sensitive to chemotherapy and/or radiation therapy than are NSCLCs [20], [21]. One challenge in proper classification and treatment of lung cancer is the extreme heterogeneity caused by differing genetic, biological, and clinical properties, including response to treatment, with over 50 histological variants recognized by the WHO typing system [22], [23]. Because of this, correct classification of lung cancer cases is necessary to assure that patients receive optimum management [24].…”

A case of combined small cell lung carcinoma with unique morphology: Investigation of tumorigenesis

“…Although our histological and immunohistochemical findings suggest that SCLC gave rise to the SLC, which in turn gave rise to the SpCC, this could not be confirmed with the molecular study. To date, there have been several molecular studies of cSCLCs . Most suggested that the SCLC and non‐SCLC components of cSCLCs had the same origin: they had identical mutations in the p53 and EGFR (exon 21) genes, as well as common LOH at 3p .…”

“…To date, there have been several molecular studies of cSCLCs . Most suggested that the SCLC and non‐SCLC components of cSCLCs had the same origin: they had identical mutations in the p53 and EGFR (exon 21) genes, as well as common LOH at 3p . In a study by Zhao et al ., approximately 75% of the mutations examined by next‐generation sequencing were shared between SCLC and non‐SCLC components .…”

“…When pure SCLC and cSCLC areas are both present, is the pure SCLC a more advanced state of cSCLC (or vice versa)? Several studies have examined cSCLC tumorigenesis via molecular analyses . However, to date, none have examined this process by comparing cSCLC and pure SCLC areas.…”

“…Several studies have examined cSCLC tumorigenesis via molecular analyses. [6][7][8][9] However, to date, none have examined this process by comparing cSCLC and pure SCLC areas.…”