Hybrid verrucous-squamous cell carcinoma of the ovary with synchronous squamous cell carcinoma of the endometrium

Verrucous carcinoma, a variant of well-differentiated squamous cell carcinoma, is usually described in the literature as arising in the oral cavity, skin, and larynx. The reports on verrucous carcinoma arising in the genital tract, usually originating in the vagina, vulva, or uterine cervix, are few. Verrucous carcinoma arising in the ovary has not been previously reported. In this article, a unique hybrid carcinoma, a large aggressive verrucous carcinoma in combination with squamous carcinoma of the left ovary and synchronously occurring with a squamous cell carcinoma in the endometrium, is presented. This unique case of a hybrid carcinoma includes the first-known case of this type of carcinoma involving the ovary. The negative cervical evaluation findings, together with the histologic patterns of the tumors in the uterus and the ovary, support the conclusion that these 2 carcinomas are synchronous, one arising in the left ovary and the other arising in the uterus.     

Image analysis in the discrimination of verrucous carcinoma and squamous papilloma.

Verrucous carcinoma is a differentiated variant of squamous cell carcinoma and may present diagnostic difficulties as it may be erroneously diagnosed as squamous papilloma. In this study, the sizes of the intermediate cells in these two conditions were measured by means of morphometric analysis. Biopsies from 28 patients with verrucous carcinoma, 25 patients with squamous papilloma, and ten squamous cell carcinomas were analysed. A significant difference was shown (P less than 0.001) by an uncorrelated t-test between verrucous carcinoma and squamous papilloma. The former had a mean cell area of 373 microns 2 and the latter 184 microns 2. Squamous cell carcinomas differed from the other two neoplasms by their large range of cell areas both within and between cases. Thus, image analysis can be of diagnostic help in cases where no firm initial histopathological diagnosis can be obtained. The diagnosis should be made on morphological grounds, but a mean cell area greater than 300 microns 2 supports a diagnosis of verrucous carcinoma whereas an area less than 250 microns 2 supports a diagnosis of squamous papilloma.     

Papillary and verrucous lesions of the oral mucosa

A variety of verrucous and papillary lesions affect the oral mucosa. Those which are benign and reactive, for example squamous papilloma or verruciform xanthoma, usually present little diagnostic difficulty. However, dysplastic and malignant verrucous and papillary lesions are a much greater diagnostic challenge, not helped by confusing terminology. Papillary hyperplasia is a reactive inflammatory condition, whereas verrucous hyperplasia is a potentially malignant dysplasia, and probably part of the spectrum of verrucous carcinoma. Papillary carcinomas, at least in the oral context, are essentially verrucous hyperplasias. ‘Oral florid papillomatosis’ is an obsolete term synonymous with verrucous carcinoma. A ‘classical’ verrucous carcinoma, with an exo-/endo-phytic growth pattern, ‘pushing’ invasive front and intact basement membrane, is easily identified, but many exophytic verrucous hyperplasias also show endophytic growth. These can also reasonably be diagnosed as verrucous carcinoma. If the lesion shows more than focal, early invasive disruption of the basement membrane, it should be diagnosed as a conventional squamous cell carcinoma.     

Double squamous cell carcinomas, verrucous type and poorly differentiated type, of the urinary bladder unassociated with bilharzial infection

A case of a 66-year-old Japanese woman with two synchronous urinary biadder tumors, namely verrucous carcinoma and poorly differentiated squmamous cell carcinoma, is described. Both tumors were accompanled by widespread squamous metaplasia in the background and unassociated with bilharzial infection. The poorly differentiated squamous cell carcinoma, having a satellite tumor in Its proximlty, was large and in an advanced stage. The verrucous carcinoma was small with minimal invasion to the muscuiaris propria. The boundary between both tumors was well defined, suggesting colliding growth appearance. Immunoexpression of cytokeratins of verrucous carcinoma was simllar to that of squamous metaplasia, and significant differences between verrucous carcinoma and poorly differentiated squamous cell carcinoma were demonstrated in thair immunoexpression of cytokeratins.     

Papillary and verrucous lesions of the oral mucosa

A wide variety of papillary and verrucous lesions can affect the oral mucosa. Benign and reactive lesions (e.g. squamous papilloma, verruciform xanthoma) usually present little diagnostic difficulty. However, premalignant and malignant verrucous and papillary lesions pose a much greater diagnostic challenge, not helped by often confusing terminology. For example, papillary hyperplasia is a reactive inflammatory condition, whereas the term “verrucous hyperplasia” is often used to describe a potentially malignant lesion, which is probably part of the spectrum of verrucous carcinoma. A classical verrucous carcinoma, with an exo-/endophytic growth pattern and a “pushing” invasive front is easily identified, but many exophytic verrucous proliferations can also show endophytic growth. These can reasonably also be considered as verrucous carcinoma and managed accordingly. The distinction becomes academic in the face of conventional invasion, when squamous cell carcinoma is the appropriate diagnosis. This review aims to summarise and highlight the key features seen in these lesions, and to provide a practical approach for tackling these entities in routine diagnostic practice.     

Esophageal carcinosarcoma with basaloid squamous carcinoma and rhabdomyosarcoma components with TP53 mutation

Carcinosarcoma of the esophagus is a rare tumor with a distinct pathological entity having squamous cell carcinoma as the most described carcinomatous component. This paper reports the first case of carcinosarcoma of the esophagus that showed predominant basaloid squamous carcinoma component in addition to squamous cell carcinoma and poorly differentiated carcinoma and sarcoma component. A 64-year-old male patient consulted for dysphasia and chest pain was examined and found to have gastrointestinal fiber-endoscope and a polypoid growth in the lower third of the esophagus. Partial esophagectomy was performed and the excised tumor showed histological features of carcinosarcoma with heterogeneous carcinomatous components with dominance of basaloid squamous carcinoma and minority of squamous cell carcinoma, poorly differentiated carcinoma, and sarcomatous component, immunohistochemically proven to be rhabdomyosarcoma. Immunohistochemical study and TP53 mutation analysis was carried out to explain the histogenesis of this rare tumor. The distinct immunohistochemical profiles of the carcinomatous and sarcomatous components suggested the possibility of transition from a carcinomatous to a sarcomatous component. The similar TP53 mutation in the carcinomatous and sarcomatous component suggested each of these components had the same origin, that is, the tumor was monoclonal in origin.     

Squamous lesions of the bladder

Squamous lesions of the bladder encompass a broad range of benign and malignant lesions. Many of the squamous lesions restricted to the urothelial surface are generally indolent, such as squamous metaplasia, squamous papilloma and condyloma acuminatum. However, some superficial lesions such as verrucous squamous hyperplasia and squamous cell carcinoma in situ may precede the development of invasive squamous cell carcinoma. Squamous lesions present within the wall of the bladder are often malignant and include classic squamous cell carcinoma and the verrucous squamous cell carcinoma and basaloid squamous cell carcinoma variants. One exception, however, is pseudoepitheliomatous (pseudocarcinomatous) hyperplasia, which is a benign mimicker of invasive squamous cell carcinoma. Our review summarizes the available data on clinical presentation, histopathologic features, differential diagnosis and ancillary tests of the squamous lesions of the bladder.     

Colliding primary lung cancers of adenosquamous carcinoma and large cell neuroendocrine carcinoma

We report an extremely rare case of primary lung cancer showing various histological elements diagnosed as the collision of an adenosquamous carcinoma and a large cell neuroendocrine carcinoma by loss of heterozygosity (LOH) analysis of the human androgen receptor (AR) and phosphoglycerate kinase (PGK-1) genes. The tumor exhibited a tiny ground-glass opaque shadow suggesting atypical adenomatous hyperplasia 18 months prior to surgery. However, the tumor grew rapidly, and the resected tumor consisted of two closely located nodules. The larger nodule was composed of well-differentiated adenocarcinomatous and moderately to poorly differentiated squamous cell carcinomatous elements, while the smaller nodule consisted of a large cell neuroendocrine carcinomatous element with partial squamoid differentiation having focal continuity with the adenocarcinomatous element. Both the adenocarcinomatous and squamous cell carcinomatous elements revealed transitional features and LOH of AR and PGK-1 genes, while the large cell neuroendocrine carcinomatous element showed a monoclonal pattern but possessed both alleles of AR and PGK-1 genes. From these clinical and pathological results, the parental cell of the large cell neuroendocrine carcinomatous element was considered to be different from that of the adenosquamous carcinomatous element.     

Verrucous carcinoma of the skin: a report on 5 Japanese cases

Verrucous carcinoma (VC) of the skin is relatively rare. The author reports 5 Japanese cases of VC of the skin. The age ranged from 63 to 91 years with a median of 70 years. The locations were hand in 1 case, lip in 1, face in 1, and foot sole in 2. The size ranged from 0.8 cm to 30 mm with a median of 1.5 cm. Grossly, all the cases showed elevated verrucous tumors. Histologically, the tumors were composed of squamous epithelial cells with minimal cellular atypia arranged in a verrucous pattern. One case showed koilocytosis. Neutrophilic abscesses were seen in 3 cases. Microinvasion was recognized in 2 cases. Focus of less differentiated squamous cell carcinoma was seen in the VC in 1 case. Actinic karatosis or squamous cell carcinoma in situ contiguous to VC was seen in 1 case. Definite precedent lesions were not recognized in any of the cases. Immunohistochemically, VCs of the skin were negative for human papilloma virus antigens in the 2 cases examined. p53 protein was expressed in all the VCs and accentuated in the basal and microinvasive parts. The Ki-67 antigen was also expressed in all the VCs, and it was mainly observed in the basal and microinvasive areas. These findings suggest that (1) VC of the skin can occur in any skin sites, (2) VC of the skin can transform into less differentiated squamous cell carcinoma, and (3) VC of the skin may be associated with squamous cell carcinoma in situ.     

Diagnostic utility of cell cycle and apoptosis regulatory proteins in verrucous squamous carcinoma.

A major problem in the diagnosis of verrucous squamous cell carcinoma is the lack of readily reproducible objective criteria for distinguishing this malignant lesion from reactive epithelial hyperplasia. Both lesions are characterized by thickened (well-differentiated) squamous epithelium without cellular atypia and subjacent stroma densely infiltrated by lymphocytes and plasma cells. This study was carried out to evaluate the use of cell cycle and apoptosis-related regulatory proteins in the diagnosis of verrucous carcinoma. The study materials consisted of representative formalin-fixed and paraffin-embedded tissue blocks from 19 cases of verrucous carcinoma, 18 classic squamous cell carcinoma, and 14 squamous epithelial hyperplasia (acanthosis). The immunohistochemical expression of the following of cell cycle and apoptosis-related regulatory proteins was evaluated using avidin-biotin complex detection technique: p16, p21, p53, Ki67, and retinoblastoma gene product (RBGP) (also known as retinoblastoma protein [pRb]). Expression of Ki67 was detected only in the single basal layer of the epithelium in all 14 cases of acanthosis. In verrucous carcinoma, Ki67 was detected in basal and suprabasal cells in the lower third of the neoplastic epithelium in 19 of 19 cases (100%). In neoplastic squamous epithelium with frankly invasive squamous cell carcinoma, Ki67 was diffusely expressed throughout the entire thickness of the epithelium as well as in the underlying invasive tumor nests. The pattern of p53 expression was similar to that of Ki67 in all the experimental groups, with a Pearson correlation coefficient of 0.98. In addition, immunohistochemical expression of p53 in the hyperplastic squamous epithelium was very weak, in contrast to the more intense immunoreactivity observed in verrucous carcinoma and classic squamous cell carcinoma. There was an overlapping in the expression of p16, p21, and RGBP in all the experimental groups, being present in more than half the thickness of the epithelium in 50% to 100% cases in each study group. We therefore conclude that the pattern of Ki67 and p53 expression in verrucous carcinoma is readily reproducible and distinctly different from that observed in epithelial hyperplasia and that seen in invasive squamous cell carcinoma. Thus Ki67, and p53 immunostains are reliable adjuncts that may be helpful in resolving diagnostic problems associated with verrucous carcinoma.     

Penile verrucous carcinoma: a clinicopathologic, human papillomavirus typing and flow cytometric analysis.

The relationship of various verruciform squamous cell proliferations of the penis such as verrucous carcinoma, with or without anaplasia and giant condyloma, is uncertain. We conducted clinicopathologic, flow cytometric, and HPV typing studies on 15 cases of penile verrucous carcinoma to investigate its place in the spectrum of genital squamous proliferations. The results show a high degree of morphologic uniformity with respect to Ackerman's original diagnostic criteria, as well as to several other histopathologic features evaluated. The latter include polygonal squamous cells with glassy cytoplasm, centrally located vesicular nuclei, intercellular edema, well-formed cellular bridges, and absence or paucity of koilocytes, true fibrovascular cores, and keratohyalin granules. Intraepithelial abscesses and crust-formation were present in many cases. Four cases contained microscopic foci of cellular anaplasia. These hybrid verrucous-squamous carcinomas presented and behaved similarly to the pure verrucous carcinomas. Tumor recurrence was correlated with extent of initial surgical management. DNA ploidy analysis by flow cytometry performed on eight pure and two hybrid tumors showed uniform diploid populations with similar G1/G2 fractions in both groups. Eight pure and two hybrid tumors evaluated for HPV by isotopic in situ hybridization were uniformly negative for HPV types 6, 11, 16, 18, and 31. The results show that penile verrucous carcinoma demonstrates characteristic and uniform morphologic features and does not contain the HPV types typically associated with condyloma acuminatum, giant condyloma of Buschke-L?wenstein, and condylomatous carcinoma.     

Sarcomatoid carcinoma (carcinosarcoma) of the esophagus with extensive areas of osseous differentiation: a case report

A 46 year old male presented with progressively increasing dysphagia and weight loss. Esophagoscopy showed a large polypoidal growth involving the middle segment of esophagus. Histologically bulk of the tumour had a sarcoma-like appearance composed of spindly pleomorphic cells along with extensive areas of bone formation. The epithelial element was represented by a small area of squamous cell carcinoma. One of the draining lymph nodes also showed small islands of squamous cell carcinoma. A diagnosis of sarcomatoid carcinoma was made. Sarcomatoid carcinoma of the esophagus, also termed carcinosarcoma, pseudosarcoma, and spindle cell carcinoma is an unusual malignant tumour of the esophagus. The proportion of carcinomatous and sarcomatous component may vary from case to case. Rarely, the sarcomatous component may exhibit osseous differentiation as in our case.     

Squamous cell carcinoma arising within verrucous carcinoma of the oral cavity: a case report

The author herein reports a case of squamous cell carcinoma (SCC) arising within verrucous carcinoma (VC) of the hard palate. An 84-year-old woman was admitted to our hospital complaining of oral discomfort. Oral examination revealed a pedunculated verrucous tumor (15 x 15 mm) in the hard palate. A biopsy revealed verrucous tumor. Resection of the lesion with wide margins was performed. Grossly, the palate tumor was pedunculated and verrucous, but a depressed area (8 x 7 mm) was recognized. Microscopically, the verrucous ares showed verrucous proliferation of squamous epithelium with little cellular atypia, and was interpreted as VC without invasion. The depressed lesion was obvious SCC with invasion. There were direct transitions between the VC and SCC. Immunohistochemically, the VC and SCC tumor cells were negative for human papilloma virus antigens. P53 protein was expressed in both VC and SCC, though the expression in SCC was much more strong and broad than that in VC. The Ki-67 antigen was also expressed in the VC and SCC, and Ki-67 labeling index ranged was 12% in VC and 64% in SCC. These findings indicate that SCC may arise within VC.     

Squamous cell carcinoma of the esophagus with cartilaginous metaplasia at metastatic lesions.

Subdermal metastatic nodules in a 62-year old male patient with esophageal carcinoma contained both carcinomatous and chondroid areas. The carcinomatous areas showed the histology of poorly differentiated squamous cell carcinoma, and light microscopically an apparent transition could be traced from carcinomatous cells to chondroid cells. In the chondroid cells, the characteristics of chondrocytes were demonstrated by light microscopic, electron microscopic, histochemical and immunohistochemical studies, although nuclear atypism was evident, suggesting their malignancy. Furthermore, immunohistochemical studies showed that some chondroid cells contained both keratin proteins and squamous cell carcinoma antigen, which were also found in the carcinomatous cells. These findings together with the light microscopic observations suggest that chondroid cells are derived from squamous cell carcinoma cells.     

Squamous Cell Carcinoma of the Esophagus with Cartilaginous Metaplasia at Metastatic Lesions

Subdermal metastatic nodules in a 62 year old male patient with esophageal carcinoma contained both car-cinomatous and chondroid areas. The carcinomatous areas showed the histology of poorly differentiated squamous cell carcinoma, and light microscopically an apparent transition could be traced from carcinomatous cells to chondroid cells. In the chondroid cells, the characteristics of chondrocytes were demonstrated by light microscopic, electron microscopic, histochemical and immunohistochemical studies, although nuclear atypism was evident, suggesting their malignancy. Furthermore, immunohistochemical studies showed that some chondroid cells contained both keratin proteins and squamous cell carcinoma antigen, which were also found in the carcinomatous cells. These findings together with the light microscopic observations suggest that chondroid cells are derived from squamous cell carcinoma cells.     

Small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone.

We report a case of primary small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone, which is unique in that the patient has remained free of tumor recurrence for 36 months after the surgery without adjuvant chemotherapy or radiotherapy. A 60-yr-old man presented himself with a right flank pain. Computed tomography revealed an ill-defined mass and a stone in the lower one third of the right ureter, and hydronephroureterosis above the stone-impacted site. The patient underwent right nephroureterectomy and stone removal. Upon gross examination, a 3.8 x 1.8 x 1.2 cm white and partly yellow mass was noted in the anterior part of the ureter, resulting in indentation of the ureteral lumen on the posterior side. Light microscopic examination revealed that the mass was mainly composed of small cell carcinoma, and partly squamous cell and transitional cell carcinomatous components. The overlying ureteral mucosa and renal pelvis also contained multifocal dysplastic transitional epithelium and transitional cell carcinoma in situ. There was no vascular invasion, and the surgical margins were free of tumor. The small cell carcinomatous component was positive for chromogranin, neuron specific enolase, synaptophysin, and pancytokeratin but negative for high molecular-weight cytokeratin (K-903) by immunohistochemistry.     

Basaloid squamous carcinoma of the larynx. A potential diagnostic pitfall

Basaloid squamous carcinoma is a rare variant of squamous cell carcinoma. It is frequently diagnosed at an advanced stage with metastases. Histologically, it is identical to basaloid carcinoma at other anatomical sites. Some authors suggest that it may be associated with second primary tumors. Others implicate the Epstein-Barr and human papilloma viruses. All reports but one warn of its aggressive biological behavior. Our case concerns a 52-year-old man who had a small lesion in his right cord. Biopsy of the lesion was performed twice, and conventional squamous cell carcinoma was diagnosed; the patient returned 2 months later with progressed metastatic disease. The patient underwent a laryngectomy and a complete clinical and immunohistochemical investigation. Basaloid squamous carcinoma is a totipotential neoplasm with a grave prognosis. It can be misdiagnosed; therefore, the authors would like to emphasize the significance of this condition in comparison to conventional squamous cell carcinoma, and we provide a review of the relevant recent literature.