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Background Spindle cell squamous cell carcinoma is an uncommon variant of squamous cell carcinoma; its diagnosis is sometimes challenging because it histopathologically resembles neoplastic or reactive spindle cell lesions of mesenchymal origins. Here, we report a rare case of spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis. Case presentation A 69-year-old Japanese man presented with pain and a polypoid mass on the lower left gingiva. He had received chemoradiotherapy for squamous cell carcinoma of the buccal mucosa 15 years prior to this consultation. In addition, he was treated for mandibular osteonecrosis 6 years after chemoradiotherapy without evidence of cancer recurrence. A biopsy revealed atypical spindle or pleomorphic cells scattered in the edematous and fibrin-rich stroma; however, no malignant squamous components were apparent. These atypical cells frequently contained neutrophils within their cytoplasm that formed cell-in-cell figures. Immunohistochemically, the atypical cells were negative for cytokeratins, epithelial membrane antigen, and E-cadherin, but positive for p63, vimentin, and p53. Although these findings suggested spindle cell squamous cell carcinoma, it was difficult to reach a definitive diagnosis. Based on a clinical diagnosis of a malignant tumor, the patient underwent a hemimandibulectomy. The surgically resected specimen had a typical spindle cell squamous cell carcinoma histology consisting of biphasic spindle cells and conventional squamous cell carcinoma components. Moreover, the surgical specimen also exhibited spindle tumor cells that frequently included neutrophils, around which intense staining for lysosomal-associated membrane protein 1 and cathepsin B was observed. This suggested that the cell-in-cell figures represent active neutrophil phagocytosis by tumor cells, and not emperipolesis. Conclusion The presence of neutrophil phagocytosis may be a potent indicator of malignancy.

A polypoid mucosal lesion in the oral cavity generally signifies a soft tissue pathology that is benign. The aetiology can vary from inflammatory conditions to fibrous tumours. Occasionally a malignant lesion can manifest as a polypoid oral mucosal lesion [1]. We would like to describe a case of a rare variant of squamous cell carcinoma, a spindle cell squamous cell carcinoma (SpSCC), presenting as a polypoid mucosal lesion. It is important to ascertain a diagnosis based on history and clinical examination, so that vital findings are not missed and speedy treatment can be instituted.

Spindle cell squamous cell carcinoma (SCSCC) represents a rare, dedifferentiated form of conventional squamous cell carcinoma (SCC) with propensity for head and neck. Morphological heterogeneity of this tumor poses significant diagnostic challenge for pathologists. This study aimed to evaluate detailed morphological and immunohistochemical (IHC) characteristics of a series of SCSCC cases. All head and neck SCSCCs diagnosed over seven years were retrospectively analyzed to assess morphological features in detail with evaluation of possible differential diagnoses. Elaborate IHC panel was performed in each case. Eleven cases (8 males, 3 females) were included. Most patients were in 5th to 7th decade. Oral cavity (n = 6; 54.5%); oropharynx (n = 3; 27.3%), and larynx (n = 2; 18.9%) were involved. Tumors were polypoidal (n = 6), ulceroproliferative (n = 3), or ulceroinfiltrative (n = 2). Microscopically, epithelial ulceration was common (90.9%). Squamous differentiation was evident on light microscopy in 6 (54.5%) cases as surface dysplasia (n = 1; 9.1%), infiltrative tumor (n = 4; 36.4%), or both (n = 1; 9.1%). The spindled tumor component showed markedly heterogeneous morphology mimicking mesenchymal malignancies or benign mesenchymal proliferations. IHC for epithelial markers (CK, EMA, p40, and p63) established epithelial differentiation in 40% (2 of 5) cases where it was not evident morphologically. CK showed highest positivity followed by p40 and p63. Aberrant mesenchymal marker expression was variably seen. Morphological diagnosis of SCSCC is challenging with several histological mimics. Surface dysplasia and component of invasive SCC in a predominantly spindled tumor are important subtle morphological clues. Systematic morphological approach aided by IHC is helpful in clinching the accurate diagnosis.

PRESENTATION OF CASE A 33-year young male presented with chief complaints of an ulcerated lesion in right inguinal region for 4-months. Patient was apparently asymptomatic 4-months back when he had swelling the size of a lemon in the right inguinal region, associated with continuous dull aching pain, non-radiating and not associated with bowel or bladder complaints. The swelling gradually progressed in size and subsequently developed an ulcerated irregular lesion involving inner aspect of the entire thigh with necrotic slough and pus discharge. There was no history of weight loss, loss of appetite or breathlessness. There were no other significant systemic illnesses. Patient was a chronic smoker for 15- years, non-alcoholic and directly exposed to sun for prolonged periods due to occupational reasons. Systemic examination was normal. All haematological and biochemical parameters were within normal limits. On examination, there was a confluent asymmetric ulceroproliferative lesion of size 20×15 cm, involving inner aspect of right thigh and groin with serosanguinous discharge. The neoplastic cells illustrated wide spread positivity for cytokeratin (CK), epithelial membrane antigen (EMA) and vimentin immunocytochemical stain, while stain for leucocyte common antigen (LCA) was negative. Magnetic resonance imaging revealed a lesion in right inguinofemoral region of 14×3 cm in transverse and antero-posterior diameters. The lesion is seen in cutis and infiltrates the subcutaneous tissue. Multiple prominent and mildly enlarged bilateral inguinal nodes are seen with lesion seen in right half of sacrum. The histopathological appearance, IHC profile of the biopsy tissue and MRI scan confirmed the diagnosis as spindle cell squamous cell carcinoma, stage IV. Subsequently patient received palliative radiotherapy of 800 cGy single session to the involved site with adequate margins by Co-60 external beam radiotherapy and received pain palliation to some extent. However, given the patient’s poor functional status and very rapid progression of the disease, the patient elected to get discharged and was lost to follow-up.

Background. Cutaneous squamous cell carcinoma is a common type of skin cancer, with aggressive metastatic or locally advanced disease representing an uncommon minority of presentations. Emerging data have supported the Food and Drug Administration approval of the anti-PD1 human monoclonal antibody cemiplimab in select patients with advanced disease. However, there is limited data regarding durability of effect and generalizability of anti-PD1 effectiveness across therapies. Additionally, information regarding applicability of these regimens to the rare spindle cell variant and to central nervous system metastases for cutaneous squamous cell carcinoma is unfortunately limited. Case Presentation. A 72-year-old gentleman presented with facial neurological deficits and a dermal nodule and was diagnosed with spindle cell squamous cell carcinoma with perineural invasion. His course was notable for early intracranial metastasis with progressive neurological deficits despite recurrent radiation therapy with intermittent response. When progressive left-sided weakness prompted imaging evaluation that was concerning for disease recurrence after exhaustion of radiation therapy options, the patient was started on systemic therapy with the anti-PD-1 monoclonal antibody treatment prior to the approval of cemiplimab. Pembrolizumab was chosen due to the fact that the patient was ineligible for clinical trials and for its every 21-day dosing. With this treatment, he has achieved a durable clinical response, resulting in near resolution of neurological deficits and more than a year of progression-free survival to date, despite aggressive intracranial disease. Conclusions. This case suggests that anti-PD-1 therapy with pembrolizumab may represent an effective and well-tolerated treatment for patients with metastatic spindle cell squamous cell carcinoma including patients with metastatic disease to the central nervous system.

Cutaneous squamous cell carcinoma (cSCC) is a malignant neoplasm of the skin characterized by an aberrant proliferation of keratinocytes. Cutaneous SCC is the second most common malignancy globally, and usually arises in the chronically sun-damaged skin of elderly white individuals. From a pathologist's perspective, it is important to differentiate cSCC from the benign and reactive squamoproliferative lesions and identify the high-risk features associated with aggressive tumor behavior. In this article, we provide an up-to-date overview of cSCC along with its precursor lesions and important histologic variants, with a particular emphasis on the histopathologic features and molecular pathogenesis.

Poorly differentiated, cytologically malignant, spindle cell neoplasms of the skin may present a diagnostic challenge with important clinical consequences. In particular, the distinction between poorly differentiated cutaneous spindle cell squamous cell carcinoma (SpSCC) and atypical fibroxanthoma (AFX) remains controversial, but with important clinical implications: SpSCC exhibits an increased tendency for both local recurrence and metastasis compared with AFX. AFX is generally accepted as a diagnosis of exclusion based on negativity for a broad panel of immunohistochemical markers, including multiple cytokeratins, melanocytic markers, muscle markers, and vascular markers. As cytokeratins can also be occasionally lost in SpSCC, it would be of tremendous diagnostic value if there were additional specific markers to facilitate the distinction of lineage in this differential diagnostic context. Initial studies demonstrated p63 to be of utility in distinguishing AFX from SpSCC; however, p63 has proved to lack specificity, as it also exhibits variable reactivity in a subset of AFX. Recent studies have shown p40 immunohistochemistry to be a more specific marker than p63 for the designation of squamous differentiation in carcinomas involving other organ systems. In the current study, we define the utility of p40 immunohistochemistry among common cutaneous spindle cell malignancies, and, specifically, we compare the diagnostic accuracy of p40 and p63 in distinguishing AFX from SpSCC. We show that p40 and p63 exhibit comparable sensitivity, but p40 exhibits superior specificity in the distinction of AFX from SpSCC.

Spindle cell squamous cell carcinoma (SCSCC) is a rare subtype of squamous cell carcinoma (SCC) that was first reported around 1900. Its potential for metastasis is uncertain. There has been noted a relationship to previous exposure to radiation therapy with subsequent aggressive presentation. We report an unusual case of a widely metastatic, poorly differentiated cutaneous spindle cell neoplasm with a rapidly progressive clinical course and dismal outcome in several days. This is one of a very few cases in the literature in which a skin cancer recurs with such diffuse metastasis and disastrous outcome.

Background: The role of CD10 needs clarification in a broader immunohistochemical battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell squamous cell carcinoma (sSCC). Methods: We retrospectively reviewed 23 cutaneous spindle cell tumors previously classified as AFX (n = 11) or as sSCC (n = 12). Each tumor was stained with CD10, S-100, p63 and two or more cytokeratin stains. Defining AFX as a diagnosis of exclusion based on multiple negative cytokeratin stains and negative p63 staining, we reclassified four squamous cell carcinomas (SCCs) as AFX. CD10 staining was reviewed and graded in all tumors. Results: Fifteen tumors were classified as AFX. Strongly positive CD10 staining was observed in all 15 AFXs, as well as four (50%) of the eight SCCs. Expression of p63 was seen in six sSCCs (75%). Conclusions: CD10 is consistently expressed by AFX. However, CD10 is also often strongly expressed by sSCC. Positive staining with p63 favors a diagnosis of sSCC. An immunohistochemical battery useful for distinguishing AFX from sSCC may include CD10, p63 and two cytokeratin markers. However, CD10 alone should not be relied upon in the distinction of these entities. Wieland CN, Dyck R, Weenig RH, Comfere NI. The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma.

Spindle cell carcinoma (SpCC) is a biphasic tumor composed of conventional squamous cell carcinoma and a malignant spindle cell component. SpCC expresses both epithelial and mesenchymal markers by immunohistochemical analysis. There is mounting evidence for sarcomatoid transformation from the epithelial component, supporting the theory that SpCC is a monoclonal neoplasm originating from a stem cell giving rise to both components. The loss of E-cadherin and the gain of N-cadherin expression are known as the “cadherin switching”. Cadherin switching is a major hallmark of epithelial-mesenchymal transition (EMT). EMT is a crucial process in cancer progression providing cancer cells with the ability to escape from the primary focus, to invade stromal tissues and to migrate to distant regions. Although E-cadherin down-regulation is well known in various cancers, there are a few studies on N-cadherin expression in cancer. Here, therefore, we investigated N-cadherin expression in the progression of head and neck SpCC. First we examined cadherin swithching in our established SpCC cell lines, SpCC-1 and SpCC-2. SpCC-1 and SpCC-2 cells were spindle in shape and showed cadherin switching. Moreover, we examined N-cadherin expression in 15 SpCC cases by immunohistochemistry. Although N-cadherin expression was not observed in non-neoplastic squamous epithelium, high expression of N-cadherin was observed in 10 of 15 SpCC cases. Interestingly, 6 of 7 SpCC cases with metastasis showed high expression of N-cadherin. In conclusion, our findings suggest that N-cadherin may play an important role in metastasis of SpCC in addition to the pathogenesis of SpCC of the head and neck.

Spindle cell squamous cell carcinoma (SpCC) is a poorly differentiated subtype of squamous cell carcinoma (SqCC). We report a case with second primary oropharyngeal SpCC after seven years of complete treatment of SqCC. The patient underwent surgery and adjuvant chemoradiotherapy. Relevant literature about SpCC was reviewed.

We report the case of an 85-year-old man who presented with an enlarging tumor on the right temple. Histologically, spindle-shaped cells were proliferating continuously within well-differentiated squamous cell carcinoma that was immunohistochemically negative for vimentin and alpha-smooth muscle actin (ASMA) but positive for cytokeratin (AE1/3). These spindle-shaped cells expressed vimentin and ASMA but not cytokeratin (AE1/3). Intermediate cells with round nuclei and small amounts of cytoplasm displayed slight expression of vimentin, ASMA, and cytokeratin. This case illustrated spindle cell squamous cell carcinoma with mesenchymal metaplasia of malignant epithelial cells.

75歳, 男性。4ヵ月前に左外眼角に圧痛を伴う結節が出現し, 徐々に増大したため近医を受診, 生検で有棘細胞癌と診断された。初診時左外眼角部に直径12mmの腫瘤を認め, 表面は凹凸不整, 辺縁は堤防状に隆起し中央には潰瘍を形成していた。腫瘍から内側1cm, 外側1.5cm離し上下眼瞼は全層, 外側は眼輪筋を含め, 眼窩隔膜, 骨膜上で切除した。病理組織学的所見では角化傾向を伴う腫瘍細胞が増殖する部分と異型を有する紡錘形細胞が増殖する部分が存在し筋層まで浸潤していた。以上より紡錘形細胞型有棘細胞癌と診断した。内側の下眼瞼の一部を皮下茎皮弁として下眼瞼縁を再建し, 頬部全体に及ぶ皮弁をデザインし皮弁外側を回転し上眼瞼の欠損と外眼角の再建を行った。下眼瞼の欠損した瞼板の再建に耳介軟骨移植を行った。術後1年で再発, 転移はない。

We reported a case of spindle cell squamous cell carcinoma.The patient was a 73-year-old man who developed an ulcerated nodule, 2.8×2.0cm in size, on the burn scar of the head. Histologically, the tumor was composed of disorderly arranged atypical spindle cells, and mitotic figures were often found. Immunohistological studies showed positive reaction of these cells for vimentin and CAM5.2. [Skin Cancer (Japan) 2001; 16: 251-254]

A case of a 28 year-old Chinese male who presented with a rapidly growing tumor within a nevus sebaceous on his right cheek. The tumor was excised and immunohistochemical analysis and histology were consistent with spindle-cell squamous cell carcinoma. To the best of our knowledge, it is the first report of cutaneous spindle-cell squamous cell carcinoma developing in nevus sebaceous in the English literature. This report highlights the importance of early excision of any nevus sebaceous with a history of change.

We describe A 81-year-old woman with spindle cell squamous cell carcinoma (SCC) on the head, which arouse from old burn scars existing for 73 years. The tumor was an ulcerated nodule measuring 2.7×1.8×1.1cm in size. The tumor was surgically excised with a 1.5cm safety margin under general anesthesia. Histologically, the tumor was composed of atypical spindle cells which arranged in a storiform pattern. However, a direct transition from squamoid cells to spindle cells was observed. Immunohistochemical study revealed the positive expression of epithelial membrane antigen, keratin and involucrin in the squamoid cells. In contrast, involucrin was weakly positive in spindle cells.

85歳の女性。約1年前より右頬部に疣状皮疹が存在した。2, 3ヵ月前より増大し小腫瘤を形成した。腫瘍細胞は主に線維芽細胞様細胞からなっており, 花むしろ様構造を呈していたが, 光顕的に明らかに扁平上皮癌と考えられる部分に連続している点, 免疫組織化学的に一部の紡錘型の腫瘍細胞にサイトケラチンが陽性であった点, 電顕的にデスモゾームやトノフィラメントを認めた点から防錘状有棘細胞癌と診断した。本邦報告例20例について免疫組織化学的態度を比較検討したところ免疫組織化学的にケラチンは記載のあったもの17例中13例(76.5%)で陽性, ビメンチンは記載のあったもの10例中8例(80%)で陽性であった。ビメンチンが陽性の症例に, 術後, 早期に再発·転移を起こしているものがあり, ビメンチンの発現は脱分化の反映及び悪性度との相関の可能性を示唆していた。紡錘状有棘細胞癌の場合, amelanotic melanoma, malignant fibrous histiocytoma, atypical fibroxanthoma等との鑑別が難しいことがあるが, 免疫組織化学的所見及び電顕所見が診断確定の手助けになると思われた。

A 76-year-old woman visited our department for the granulomatous tumor on her nose on October 6, 1992. She noticed a papule on her nose 5 months ago and it had gradually grown. A 16×12×3mm sized, oval shaped, ulcerated, pale pink colored, granuromatous tumor with slight bleeding was seen on her first visit. Spindle cell squamous cell carcinoma was diagnosed histologically for the tumor. The tumor was composed of mainly spindle-shaped cells with large, atypical, round nuclei and tumor cells arranged like a stream. Immunohistological staining of the tumor showed anti-keratin antibody positive, anti-melanoma antibody and vimentin both negative. The tumor cells was S-100 negative, however, plenty of S-100 positive dendric-shaped cells infiltrated among the tumor cells.

BACKGROUND Cutaneous squamous cell carcinoma is a disease that has a multitude of clinical, histologic, and dialogic subtypes, all of which are of significance to the clinician. OBJECTIVE Ten of the most common and clinically significant subtypes of squamous cell carcinoma are presented to emphasize the clinical importance of each and to emphasize and contrast their differences. METHODS The literature of each subtype of squamous cell carcinoma is reviewed and capsulized. RESULTS Appropriate diagnosis, therapy, and postoperative management of all subtypes of squamous cell carcinomas are dependent upon the understanding of their unique characteristics. CONCLUSION The 10 common variants of squamous cell carcinoma presented in this paper: neurotrophic squamous cell carcinoma, Bowen's disease, squamous cell carcinoma in transplant patients, keratoacnnthoma-like squamous cell carcinoma, squamous cell carcinoma of the lip, adenoid squamous cell carcinoma, spindle cell squamous cell carcinoma, radiation-induced squamous cell carcinoma, verrucous carcinoma, and Marjolin's ulcer, have unique etiologic, histologic, and clinical features that significantly influence their diagnosis, treatment, and subsequent management. It is imperative that physicians responsible for the care of these patients understand the implication of these unique characteristics.

A case of spindle cell squamous cell carcinoma of the tongue in a 4-year-old boy is presented. The diagnosis is supported by immunohistochemical demonstration of cytokeratins within the tumor cells. The authors believe this report represents the first case of “nonkeratinizing” spindle cell squamous carcinoma of the tongue in the first decade of life.

74才男子。1年3ヵ月前より右頬部に小腫瘤が出現し, 最近3ヵ月で, 小鶏卵大となつた。病理組織所見では, HE染色でstoriform pattern, bimorphic patternを呈し, 鍍銀染色で“箱入り像”を呈したこと, acid phosphatase活性陽性より, malignant fibrous histiocytomaを疑つた。しかし脂肪染色, α1-antitrypsin, α1-antichymotrypsin陰性であり, 抗ケラチン抗体にて一部陽性, さらに電顕にて腫瘍細胞にデスモゾーム·トノフィラメント複合体を認めたので, squamous cell carcinomaの特殊型であるspindle cell squamous cell carcinomaと診断した。