Primary Squamous Cell Carcinoma of the Gallbladder with Hepatic Invasion: A Case Report

The aim of this study is to analyze and compare the immunohistochemical expression of cathepsin B in primary oral squamous cell carcinoma (OSCC) and recurrent OSCC. A total of 50 cases were studied immunohistochemically for rabbit polyclonal antihuman cathepsin D expression. A total of 10 cases of breast carcinoma were taken as positive controls. Immunohistochemical staining was performed using labeled streptavidin-biotin technique. All the 45 cases of OSCC, both primary and recurrent cases included, showed varying grades of cathepsin D immu-noreactivity. Statistical significance at 5% level was observed in cathepsin D expression between the different grades of well, moderate, and poorly differentiated primary squamous cell carcinomas. In the comparison of cathepsin D staining intensity among primary squamous cell carcinomas with and without recurrence, a statistical significance between the groups was observed when the p-value was at 10%, but the same comparison was not significant when the p-value was at 5%. Cathepsin D expression in primary squamous cell carcinomas with recurrences was very variable as compared with primary squamous cell carcinomas without recurrences. Comparison of cathepsin D expression in primary with their recurrent counterparts showed mostly similar intensity of expression in recurrent carcinomas, thus suggesting its limited usefulness in predicting recurrence. Although cathepsin D might have shown limited usefulness in predicting cancer recurrence, it, however, is a proven valuable tool to detect the aggressiveness of various other tumors, and if corroborated with a larger sample may hold the key to early, more effective, and more specific treatment modalities for cases of oral cancer also.

Primary intracystic squamous cell carcinoma (SCC) of the breast is an extremely rare entity and has a low incidence in comparison with other breast cancers. We report a rare case of primary intracystic SCC in a 45-year-old woman who presented with a cystic lump in the right breast. Cytological smears of the fluid aspirated from the breast tumor revealed malignant squamous cells dispersed in single and occasional groups along with numerous cyst macrophages, suggesting cystic SCC. Histological study of the mastectomy specimen confirmed the diagnosis of primary intracystic SCC. Although the presence of abundant foamy macrophages in the background of fine needle aspiration cytology smears of the breast suggest benign breast lesion, when associated with malignant squamous cells, these suggest cystic primary SCC or metastatic SCC. The primary SCC should not be confused with metaplastic change in other breast carcinomas.

Carcinomas are malignant tumours of epithelial origin. Cutaneous carcinomas are primarily of keratinocytic origin (epidermal or follicular keratinocytes) or of adnexal glandular origin. Keratinocytic carcinomas include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (SCC). BCC and SCC are by far the most common forms of cancer in humans. Paradoxically, as they are not generally recorded in cancer registers, their importance in terms of public health and their economic impact on healthcare systems are widely underestimated. The relative incidences of BCC and SCC differ according to whether SCC is grouped among lesions with the same oncogenesis or not, namely actinic keratosis (AK) and Bowen's disease (BD) (see below). If AK is included in this group, SCC is the most common form of human cancer. If it is excluded, while being responsible for the majority of deaths attributable to non-melanoma skin cancers (NMSC), SCC is the second most important form of cancer in terms of frequency. Although the majority of SCC cases are not life-threatening, this carcinoma is likely to metastasize, particularly if initial treatment was inadequate. The SFD has drawn up guidelines for the treatment of BCC (2004) and melanoma (2005). The present work is the logical continuation of this initiative. It aims to provide practitioners treating skin cancer patients with a series of recommendations based on scientific evidence or, when this was not available, on expert consensus. Medical textbooks refer to a wide array of clinical and histological forms of SCC. The prognosis for these different forms varies according to whether therapy has been specifically codified or not. In addition, the terminology used to describe these lesions varies, which may lead to confusion and prevent use of a clear decision-making tree. The TNM classification, developed by AJCC/IUAC/UICC, which is used for all skin cancers except melanoma, is not suitable for SCC. It does not take into account the multiple prognostic criteria identified in the literature. Many treatments are currently available, in particular, for SCC precursor lesions, but the criteria of choice and the methods of application are generally far from clear for practitioners. This results in major disparities in terms of therapeutic management. The present guidelines deal with the treatment of SCC and precursor lesions in immunocompetent adults in France, in both ambulatory and hospital settings. The aims are as follows: to clarify the terminology used to describe the different forms of SCC and of their precursors AK and BD; to propose a prognostic classification of SCC that takes into account various clinical and histological factors; to recommend diagnostic and therapeutic measures for SCC based on previously identified prognostic factors; to optimize diagnostic and therapeutic management of AK and BD in accordance with recent data in the literature; to provide an overview of the principles for primary prevention of SCC and precursor lesions (based on the same methods), and for screening of subjects identified as at risk for SCC (other than genodermatosis and immunosuppression). Due consideration has been given to the fact that patients with SCC, AK or BD are generally (very) elderly. This creates problems in terms of screening for lesions, and for amenability to care and treatment (poor compliance to certain treatments, difficulty in carrying out sequential physical treatments, refusal of onerous surgery, or surgery requiring multiple operations). The oncogeriatric dimension of therapy has thus been taken into account. These guidelines do not address the following issues: SCC of the nails or the genital and anal mucosa; SCC in immunosuppressed patients, particularly transplanted patients; SCC in the context of certain genodermatoses. The levels of evidence and grades used are those defined by the HAS [French Health Authority] (Annex 1). The literature on SCC generally carries low levels of evidence and, except where otherwise stated, the recommendations included in these guidelines are of grade C. These guidelines have been created in the form of Recommendations for Clinical Practice in accordance with the ADAPTE method.2 As its name suggests, this method advocates the adaptation to a particular situation – in this case, medical practice in France in 2008 – of one or more guidelines on the same theme, drawn up previously or in other countries. Medical societies concerned with SCC were consulted on the initiative of the French Dermatology Society (SFD), the sponsor, to define the scope of the guidelines, identify work performed on the subject and recommend professional members for the organizing committee (OC), the working group (WG) and the reading group (RG). Mention must be made of the difficulty of recruiting general practitioners to these groups, despite the fact that, in view of the subject, their assistance is vital. In the Spring of 2007, the Dermatology Recommendations Association (aRED), a subgroup of the SFD, created a multidisciplinary OC on behalf of the SFD, comprising doctors in private and public practice, both university and non-university practitioners, from a variety of geographic origins. The OC then set up a WG using the same criteria of professional diversity. Members of the OC and WG were asked to complete a form indicating any conflict of interest regarding management of SCC (Annex 2). The members of the RG were recommended by medical societies, once again with the aim of reflecting the diversity of professional practice. The overall arguments, key points and recommendations were drafted by the WG following the identification and selection of previous guidelines on SCC, contextualization (occasionally critical) of recommendations contained therein and a synthetic update of the literature. Practitioners in the reading group were sent a letter asking for their opinion on the topic, including presentation of the key points and recommendations, in particular, regarding clarity and applicability. The comments made by the RG were analysed by the WG and, whenever possible, taken into consideration in the final draft. Lastly, on the 11 December 2008, the main recommendations were presented and discussed publicly in the presence of practitioners to whom the guidelines were addressed during the Journées Dermatologiques de Paris, the main French national dermatology congress. The low level of evidence in the existing literature underscores the continuing lack of knowledge about optimal management of patients with SCC. These areas represent subjects for future work by the OC and WG (see Perspectives section). I.2.1. ADAPTE method This rigorous and explicit method, recently described and published by an international group,2,3 is designed to enable the adaptation of existing guidelines, and to reduce the time, effort and cost required to create a fresh set of guidelines. Methodological guidelines concerning the use of this method were published online by HAS in March 2007.3 I.2.2. Choice of method for drafting guidelines In the spring of 2007, the SFD Bureau and the aRED decided that the ADAPTE method could be used to draft French guidelines for the management of SCC. Foreign guidelines on this topic, some of them fairly old, were already known, and ADAPTE contextualization was entirely possible, as these guidelines had been published by agencies or medical societies for populations and levels of health infrastructure and organization comparable with those in France. However, as the literature used for the drafting of these guidelines was deemed to be of mediocre quality, the ADAPTE method presented a number of limitations. In addition to this, several questions that have subsequently come to the fore (e.g. the nature of AK or the place of new medical treatments) occupied little or no place in the existing guidelines. Therefore, in addition to adaptation, updating of the literature proved necessary. I.2.3. Definition of the scope of the guidelines The limits of the SCC topic were discussed in conference calls between members of the OC in July 2007. The PIPOH checklist3 used to define the scope and target audience of the guidelines was as follows: P (patient population) = French population of both sexes; I (interventions) = prevention, screening, diagnosis, treatment and monitoring; P (professionals) = specialists responsible for diagnostic and therapeutic management of SCC, general practitioners (GPs), occupational therapists as well as specialists involved in the screening and follow-up; O (outcomes, the evaluation criteria used for the recommendations) = levels of treatment response in terms of remission, local relapse, remote metastasis and mortality, when these parameters were available; H (healthcare setting) = ambulatory or hospital. In addition to diagnosis and curative treatment of SCC, it was decided to include: screening of subjects identified as at risk for SCC (excluding genodermatosis and immunodepression); cutaneous or cutaneous-mucosal sites on the borderline of dermatology: eyelids and vermilion border of the lips; lesions considered precancerous and keratoacanthoma. These lesions are histogenetically related to SCC and have been dealt with in several recent studies of medical and surgical therapies. However, genital and anal sites in both genders were ruled out as these are normally dealt with by gynaecological surgeons, urologists, gastroenterologists or digestive surgeons. Ungual sites were similarly ruled out. In addition, it was decided not to include SCC observed in immunosuppressed organ transplant recipients, as guidelines for the management of these patients were being drawn up under the auspices of the HAS.4 I.2.4. Documentary research In late June to early July 2007, Mrs J. Brugneaux performed a literature search for practical guidelines on SCC and precursor lesions using systematic surveys of medical bibliography databanks (Annex 3) and looking out for guidelines, consensus conferences, articles on decision-making process, systematic reviews, meta-analyses and other national and international evaluation studies. Relevant websites (government agencies, medical societies, etc.) were also explored. Documents not accessible by the standard diffusion circuits ('grey literature') were consulted using every available means. Legal and regulatory texts on this subject were also consulted. Only English- and French-language articles were considered eligible. Initially, the selected references were screened by L. Martin and J.-J. Bonerandi to eliminate all texts unrelated to the subject on the basis of their titles, (e.g. non-cutaneous CE of the head and neck; genital CE) and irrelevant literature (guidelines currently at project level, etc.). The remaining texts (n = 58) were submitted to all CO members in July 2007 to ensure that they were authentic guidelines, didactic articles or authors' opinions. I.2.5. Determination of questions to be covered in the guidelines At a plenary session of the OC held on 19 September 2007, the scope of the guidelines was definitively agreed upon, as were the various topics to be covered therein: clinical, pathological and epidemiological forms of SCC and precursor lesions; prognostic factors for SCC; treatment methods for SCC and precursor lesions; patient management. At 19 September 2007 meeting, a list with the following documents, theoretically amenable to adaptation, was established: Non-melanoma skin cancer: guidelines for treatment and management in Australia. National Health and Medical Research Council. 2002 (NHMRC, Australia). Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma. British Association of Dermatologists/British Association of Plastic Surgeons. 2002 (BAD/BAPS, UK) Guidelines for management of Bowen's disease: 2006 update. British Association of Dermatologists. 2006 (BAD, UK). Guidelines for the management of actinic keratosis. British Association of Dermatologists. 2007 (BAD, UK). Basal cell and squamous cell skin cancers. National Comprehensive Cancer Network. 2007 (NCCN, US). Multiprofessional guidelines for the management of the patient with primary squamous cell carcinoma. National Guideline Clearinghouse. 2007 (NGC, US). Green A, Marks R. Squamous cell carcinoma of the skin (non-metastatic). Clin Evid 2005; 4: 2086–2090. I.2.6. Selection of guidelines for adaptation The suitability of these seven guidelines for adaptation in different areas of practice was assessed by five WG, using the simplified AGREE appraisal instrument5 (Annex 4). The NGC guidelines and the Clinical Evidence article were not used, as the former is a retranscription of the BAD 2002 guidelines, whereas the latter gives no indication of the method used for the bibliography search, and was thus deemed inconsistent with the scope of the present guidelines. The following three SCC guidelines were ultimately selected: Basal cell and squamous cell skin cancers, 2007 (NCCN); Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma, 2002 (BAD 2002); Non-melanoma skin cancer: guidelines for treatment and management in Australia, 2002 (NHMRC), together with Guidelines for the management of actinic keratoses, 2007 (BAD 2007) and Guidelines for management of Bowen's disease: 2006 (BAD 2006). I.2.7. Layout of the guidelines, key points and recommendations Each section was divided into 'items', some of which contained one or more 'key points' or 'recommendations'. An item was comprised of a topic concerning epidemiology, diagnosis or treatment amenable to targeted documentary research (e.g. prevalence of SCC among the French population; use of imiquimod in the treatment of AK). Each item was assigned to a group comprising two or three WG members, based on their experience or interest in the topic. Individual items were either identified as existing in one or more adapted guidelines, or were created anew by the WG. Items are summarized at the end of this section in a summary table showing the adapted guideline(s), where they are also discussed (Table 1). Key points comprise information items of cultural relevance which are possibly not directly related to day-to-day practice. Recommendations refer to the diagnostic or therapeutic management of patients. Key points and, wherever possible, recommendations were graded using the HAS method (Annex 1). In accordance with the ADAPTE method,6 items identified in previous guidelines were evaluated by WG members to determine the degree of concordance between the data analysed and the conclusions set out in the arguments, and between these conclusions and the recommendations proposed. Any divergence with regard to prior guidelines is indicated at the start of the paragraph. In most cases, updating of bibliographical references proved necessary, and this was carried out by Mrs J. Brugneaux (January 2008) (Annex 3). Finally, actual adaptation (drafting of the arguments, key points and recommendations) involved summarizing the proposals set out in the various guidelines and drafting the arguments suitable for medical practice in France in 2008. An initial version of the arguments and the proposed recommendations was reread and discussed in plenary sessions by the WG on 11 March 2008 and by the OC on 25 March 2008. Updating of the bibliography was suspended at this point. Opinions differed within the WG regarding a number of relevant items (prognostic classification of primary SCC, value of routine histological analysis of excision margins and hierarchical classification of therapeutic choices for precancerous lesions). In the absence of consensus within the adapted guidelines and of literature providing an adequate level of evidence, these divergent opinions gave rise to numerous e-mail exchanges and meetings until a pragmatic consensus was reached within the WG and the CO. The successive versions of the arguments attest to changes in viewpoints regarding these items. The WG stressed the need for clinical trials designed to obtain factual information which would settle these divergences. A complete argumentation framework and an initial version of the short text comprising the key points and recommendations were sent to readers during summer 2008. Final versions of the documents and of a highly synthetic pocket-sized flyer were prepared in autumn 2008. The CO and the WG are well aware that their editorial choices simply reflect medical and scientific knowledge concerning SCC and precursor lesions up to spring 2008. Follow-up on bibliography data and annual meetings of the WG are scheduled to ensure prompt modification of the guidelines following the publication of relevant diagnostic, prognostic or therapeutic information regarding SCC and precursor lesions (see Perspectives). The term squamous cell carcinoma encompasses all malignant epithelial tumours with predominantly malpighian differentiation. SCCs include primary malignant skin tumours with malpighian differentiation, and are distinct from other primary epithelial skin tumours such as BCC. The term thus covers a number of different clinico-anatomical entities, some of which only differ in terms of clinical presentation or degree of aggressiveness. The inclusion of AK and keratoacanthoma under SCC by some authors and in certain reference works is currently disputed.6 The adapted guidelines, i.e. the three guidelines dedicated to SCC (NHMRC,7 NCCN8 and BAD9) and those specifically focused on AK and BD,10,11 restrict themselves to a summary description of these entities without discussing clinico-anatomical forms and nomenclature. The WG felt it was necessary to adopt a position on this subject and therefore, the ADAPTE method was not used in drafting this chapter, for which a specific bibliographical analysis was performed. This chapter contains epidemiological overviews and proposals with regard to terminology and classification. It also describes the populations targeted by these guidelines. II.1.1. Environmental factors Exposure to sun Sunlight is the principal environmental factor, and evidence for its role in SCC relies on the appearance of lesions on the areas of skin most exposed to sun, a greater prevalence of lesions among fair-skinned subjects, a latitude gradient for populations with the same skin phototype and a higher incidence of the disease among patients working outdoors.12 The occurrence of SCC is associated with total cumulative lifetime UV dose. The most commonly affected sites include the face, back of the hands and forearms. In a Spanish study, more than 92% of SCC cases occurred in these areas.13 UVB (290–320 nm) and UVA (320–400 nm) play a role in carcinogenesis. For most SCC, UV-induced mutations are observed in the P53 gene.14 Artificial sources of UV have also been incriminated.15 PUVA therapy in excess of 200 sessions is associated with the onset of SCC. Sources of this type of radiation in tanning salons are not harmless and must be added to other risk factors.16 According to the 2005 report by the French Environmental Health Safety Agency (AFSSE), 'Evaluation of risks associated with exposure to UV radiation', the risk of skin cancer (carcinoma or melanoma) is increased by a factor 1.10 with 30 sessions per year over a 10-year period and by 1.39 with 100 sessions. Other exogenous risk factors include arsenic, pesticides, hydrocarbons, tobacco (lower lip), ionizing radiation, local factors The main factor is the skin which is The risk is higher in patients with a for In a a in that to is associated with a risk of SCC, AK and keratoacanthoma. Other risk factors The following factors are involved in than of and have been particularly in the genital and anal but also in in the of in areas that are both exposed and to and in and immunocompetent patients However, the presence of is to risk factors are in organ sun and Squamous cell carcinoma a number of malignant primary epithelial skin tumours with malpighian differentiation, and is distinct from BCC. The key factor onset of SCC, Bowen's disease (BD) or actinic keratosis (AK) is the total lifetime of UV whether or The risk of BD or SCC is affected by skin which is A number of which may be specific to particular have been such as tobacco for actinic and SCC of the as well as for genital or anal SCC. medical also to and keratosis of common lesions, particularly among subjects, in areas exposed to the sun such as the face, the back of the hands and the in subjects, and is associated with other of (e.g. etc.). is based on the clinical and is by lesions of more to the than to the with a of or with of and or In practice, AK or of AK are from multiple which come together to form the actinic is the of This particular is by the presence of tobacco as a second factor and by the of SCC in this is no histological of may be or of the The is to and is or An on with the and is a is based on the presence of various keratinocytic of by changes in the or In these in and do not the or the skin The term carcinoma in is only used when these together in a and the reference works of and The WG that these are simply of the same and, as do not classification as distinct These are not for France. The published prevalence for adults over between and in populations of the but between and in populations of the In of between and and of patients over have at one If AK may or to SCC. The of of such lesions over a period has been to be between and of A in this particular that a patient with AK has a risk of one of these AK into SCC within According to several from to of AK to SCC within of the genital form a group of AK to their and the role of in their A of gynaecological literature has the of subsequently and as well as cases observed are under the term or or according to whether they the or more than of the epithelial the is the term SCC or Bowen's disease is the between AK and lesions and that the of lesions and be in the same as their in the genital or using the term keratinocytic The WG felt that was little value in to criteria for entities with divergent and clinical It considered that were no for the clinical name of by the medical with a name that is clear to practitioners. may to grade the level of epithelial in their This to be were it not for its impact in terms of treatment and health etc.). of a that all forms of AK are in fact SCC, together with carcinoma, keratoacanthoma and other these entities are by the of mutations in However, a number of epidemiological studies have that the of AK may take three different or to SCC. The for AK is In the by Marks in the the over a period was than per The guidelines AK as precancerous However, the and BAD guidelines do not adopt a position concerning the nature of simply that most SCC to but that the risk of of AK to SCC is thus the choice of therapy for most AK described in to carcinomas of the a a and and mutations the of new primary tumours and of local the it has been that UV radiation is associated with the and of carcinogenesis. have been to be more common in areas than in have been at AK excision These clinical namely the of SCC and and only on and the of of AK in certain areas (e.g. In practice, these could treatment of the of the affected than treatment of However, no studies as the value of such an Bowen's disease Bowen's disease is an SCC. The prevalence and incidence of this disease in France and are most affected by the disease in published cases are in the of and are predominantly of the cutaneous as a which is generally or with a It is generally in areas of covered lesions In the and BD may be or and of the or forms are associated with The is with a and of and present at all by they do not the basal of BD with or have been and may be required to determine whether they are In the diagnosis with 3) is based primarily on of clinical medical presence of histological of and, in certain cases, identification of any associated This risk of has been in a and based on several studies. The risk to be between and for cutaneous and for and clinical presentation the appearance on the of an The risk to be greater than that of the common SCC AK is an of AK is associated with exposure to

BackgroundPrimary gastric squamous cell carcinoma (GSCC) is an extremely rare malignancy, accounting for approximately 0.04–0.07% of all gastric malignant tumours. The disease carries a poor prognosis, and there is currently no globally standardised treatment protocol.Case descriptionA 59-year-old female patient with no significant medical history presented with prolonged epigastric pain. Gastroscopy revealed a 5 × 7 cm ulcerated mass along the greater curvature of the gastric body; biopsy confirmed squamous cell carcinoma. Computed tomography (CT) demonstrated tumour invasion through the serosa with perigastric fat infiltration and multiple perigastric lymph nodes >1 cm (the largest node in station 10 measuring 5 cm); tumour marker CA72-4 was elevated at 29.3 U/ml. Comprehensive evaluation revealed no primary lesions at other sites, including esophagogastroduodenoscopy, colonoscopy, chest CT and physical examination. Primary squamous cell carcinoma of the gastric body, cT4N2M0. The patient underwent total gastrectomy, distal pancreatectomy, splenectomy and D2+ lymphadenectomy (including stations 12b, 12p, 13). Histopathological examination confirmed poorly differentiated squamous cell carcinoma with serosal invasion, invasion into the greater omentum, lymphovascular invasion (LVI+) and perineural invasion (PNI+), with 7/25 lymph nodes positive for metastasis. Immunohistochemistry showed diffuse positivity for p63, CK5/6 and CK7; p16 was negative. Post-operative staging: pT4bN3aM0, LVI+, PNI+. The patient received adjuvant chemotherapy with eight cycles of the XELOX regimen.ConclusionGSCC is a rare disease entity with a poor prognosis. Radical resection combined with adjuvant chemotherapy represents a reasonable approach for resectable disease. Multicentre studies and clinical trials are needed to establish optimal treatment protocols for this rare malignancy.LEARNING POINTSDiagnosis requires systematically excluding other primary squamous cell carcinoma sites (oesophagus, lung, head and neck) before confirming primary gastric squamous cell carcinoma (GSCC).Radical resection (R0) combined with aggressive adjuvant chemotherapy is the optimal treatment strategy, offering the best survival chance even in advanced disease (pT4bN3aM0, LVI+/PNI+).Treatment must be individualised due to a lack of standardised protocols: for this extremely rare malignancy, the decision between upfront surgery versus neoadjuvant chemotherapy should be based on tumour resect ability, biological characteristics and multidisciplinary tumour board discussion.

Squamous cell carcinoma (SCC) is one of the most common malignancies involving the parotid gland, but it has been recognized that the vast majority of parotid SCC represents metastases, especially from the ipsilateral facial skin. Bona fide primary SCC of the parotid is so rare that it is unclear whether it truly exists at all. We sought to molecularly characterize cases diagnosed as primary parotid gland SCC to see if they possess a unique genetic makeup.We identified cases in our archives which had been diagnosed as primary SCC of the parotid gland. In all cases, metastatic disease was excluded by a thorough history and physical examination. Cases with histologic evidence of a precursor neoplasm (e.g., carcinoma ex-pleomorphic adenoma) were also excluded. Targeted next-generation sequencing (NGS) was attempted on all cases.Six cases diagnosed as primary parotid SCC were identified, arising in 4 males and 2 females ranging from 8 to 73 years (mean, 51.8 years). All cases exhibited keratinization and unequivocal invasion. Four of 6 appeared to be arising from cystically dilated ducts. Five of 6 exhibited well-developed cellular atypia; the remaining case, while cytologically bland, demonstrated perineural invasion. Targeted NGS was successful in 5 of 6 cases. Two SCC harbored several mutations in a mutational profile reminiscent of SCCs seen in other organs. One case harbored YAP1::MAML2, a fusion previously reported in porocarcinoma and other neoplasms. One case harbored IRF2BP2::RUNX2, and presumably represents keratocystoma or SCC ex-keratocystoma. Finally, one case an increase of C > T mutations consistent with ultraviolet damage, suggesting that this case represented a cryptic metastasis from cutaneous SCC.Our analysis did not confirm a unifying genetic signature for purported primary parotid SCC. Indeed, our findings suggest that true primary parotid gland SCC is even rarer than already believed. In our 5 cases with results, NGS findings demonstrated that one was likely a keratocystoma, one a cryptic metastasis from a cutaneous SCC, and one a porocarcinoma, either metastatic or primary. The two remaining cases had complex genotypes reminiscent of SCCs from other sites. This may be the signature of genuine parotid primary SCC, but metastasis from an SCC from another organ cannot be excluded. Accordingly, a diagnosis of primary parotid gland SCC should be viewed with skepticism.

Primary squamous cell carcinoma (SqCC) of the breast, which represents <0.1% of all breast cancers, is rare and diagnostically challenging, possibly having high mortality due to its large size, distant metastasis, and rapid progression. Bagged silicone possibly induces primary breast SqCC. Liquid silicone gel was replaced with bagged silicone breast implants; however, this was warned about by the FDA on March 8, 2023. This case details primary SqCC of the breast in an 81-year-old postmenopausal Asian woman with a history of bilateral liquid silicone gel injections in her 20s. She exhibited local heat, swelling, and mild erythema in the left breast. Chest computed tomography (CT) showed a 10.3 cm left breast tumor with lymph node and bilateral lung metastases, significant calcifications around the silicone injection sites, and pathological findings of squamous cell carcinoma with keratinization. (Figure 1) Tumor markers revealed elevated serum SqCC antigen at 28.0 ng/mL, with normal CEA and CA15-3 levels. Treatment included a left modified radical mastectomy and sentinel lymph node biopsy, with negative estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and GATA Binding Protein 3, and a Ki-67 index of 15%. Primary SqCC of the breast, representing less than 0.1% of all breast cancers, is rare and diagnostically challenging. The 2003 WHO classification mandates three criteria for diagnosing breast SqCC: (1) Exclusive presence of SqCC without other neoplastic changes, (2) Absence of SqCC at any other primary site, and (3) No overlying skin or nipple involvement. Literature indicates that early-stage breast SqCC typically has a favorable prognosis, yet lacks specific diagnostic and management guidelines.1 These tumors are often hormone and HER2 receptor negative, as seen in our case.2 Our case, with the largest reported primary breast SqCC (10.3 cm), underscores the lack of standardized treatment protocols. Despite the absence of formal guidelines, our patient underwent surgical treatment without subsequent chemotherapy, radiation, or hormone therapy. However, Aparicio et al. reported no survival advantage for SqCC patients receiving neoadjuvant or adjuvant chemotherapy, in comparison to those who did not receive chemotherapy, highlighting the need for tailored treatment strategies.3 However, silicone gel injections, once popular in Taiwan, have been associated with complications like mastitis, sarcoma, and systemic issues such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA) also called human adjuvant disease (HAD) indicate liquid silicone dissemination may lead chronic inflammatory status due to silicone spread.4 Our case reveals long-term risks including significant calcification and chronic inflammation surrounding the injected silicone gel parcels on CT scans, which induces squamous cell metaplasia in future (Figure 1). This case supports the notion that breast SqCC can occur following silicone injections. Microscopically, the breast tissue was infiltrated by invasive carcinoma with squamous differentiation, exhibiting varying degrees of nuclear atypia and prominent keratinization. These neoplastic cells were interspersed with numerous vacuolated cavities and empty spaces of different sizes. In the surrounding mammary tissue, an exuberant foreign body reaction was observed, characterized by the presence of multinucleated giant cells and lymphocytic infiltration. Based on the patient's clinical history and the morphological findings, it is suggested that the occurrence of squamous cell carcinoma in the breast is associated with the silicone injection (Figure 1).5 This report highlights a case of SqCC linked to silicone gel injections and the largest SqCC currently reported; however, the latent population numbers who received silicone gel injection was unclear, when the injection was popular in Taiwan, the part of population may had received silicone gel injection by non-authorized medical professional, thus not officially recorded. Owing to the benign appearance on mammograms and ultrasounds, individuals who received silicone gel injections may require additional screening methods such as SqCC tumor marker assessment and magnetic resonance imaging/CT studies and guided biopsy to suspicious lesion. In conclusion, this case of primary breast SqCC following silicone gel injection emphasizes the urgent need for research on the link between silicone gel, implants, and SqCC development in the breast. This highlights the carcinogenic risk associated with liquid silicone gel injections, as evidenced by the high occurrence of SqCC. This case report responds to a recent FDA warning and emphasizes the need for heightened awareness and screening of individuals with past silicone gel injections. All authors declare no conflict of interest.

This manuscript aims to describe an unusual case of multiple second primary squamous cell carcinomas (SCCs) in several sites of the oral mucosa in a nonsmoker and nondrinker woman and to discuss the diagnostic criteria, clinicopathological aspects and outcome of second primary tumor (SPT). Patients treated for SCC of the head and neck are at high risk for developing SPT arising from the same dysplastic mucosal feld. Currently, there is no reliable method to predict which of the patients will develop SPT. A 64-year-old nonsmoker and nondrinker woman developed several second primary oral SCCs in 7 years of follow-up, most of them being synchronic, treated by surgery without and with chemotherapy and radiotherapy. Patients treated for SCC require a long-term and careful follow-up as the development of SPT contributes with significantly negative impact on the prognosis. This report describes the diagnosis and management of a very unusual case of several SPTs affecting different sites of the oral mucosa in the same patient. Moreover, the patient had no apparent risk factors associated with the development of the oral cancer. Therefore, a brief update concerning SPT and its diagnosis and management is also provided.

Primary Squamous Cell Carcinoma (SCC) of pancreas is a non endocrine tumour showing ductal origin which accounts for approximately 0.5-2% of all malignant pancreatic tumours. Diagnosis is usually made by tissue sampling followed by comprehensive search for primary SCC elsewhere. Hereby, authors report a rare case of primary pancreatic SCC in a young female. A 46-year-old female with history of type 2 diabetes mellitus presented with abdominal pain radiating to back associated with biliary vomiting since five months. Laboratory investigations revealed mild anaemia, neutrophilic leucocytosis and elevated blood glucose. Carcinoembryonic Antigen (CEA) and Cancer Antigen 19-9 (CA 19-9) were within normal limits. Contrast-Enhanced Computed Tomography (CECT) (abdomen and pelvis) showed pancreatic atrophy, multiple stones in head and body along with a pseudocyst in tail of pancreas. Patient underwent triple phase Magnetic Resonance Imaging (MRI) with Magnetic Resonance Cholangiopancreatography (MRCP) which showed chronic pancreatitis with intraductal calculi in the head and distal body region with pseudocyst at tail region. Frey’s procedure was done and tissue sent in multiple pieces. Histopathology revealed features of infiltrating SCC in a background of atrophic pancreas. Immunohistochemistry for CK5/6, P63 and CEA was done for confirmation. It showed strong positivity for CK5/6 and P63, while CEA was negative. Final diagnosis of SCC of pancreas in a background of atrophic pancreas was rendered. Though pancreas is devoid of squamous cells, it is not uncommon to find squamous metaplasia of ductal epithelial cells secondary to chronic inflammation. In the present case, though clinical and radiological features points towards benign lesion, definite diagnosis as SCC is justified by histopathology and immunohistochemistry. Because of the rarity, diagnosis and treatment still remains a challenge.

Pure primary squamous cell carcinoma of the ovary: a case report and review of the literature

Introduction: Primary squamous cell carcinoma (SCC) of the small intestine is an exceptionally rare malignancy, with limited cases reported in the literature. The rarity of this condition, combined with nonspecific clinical manifestations, poses significant diagnostic and therapeutic challenges. Case Presentation: We report the case of a 47-year-old woman who presented with a 2-month history of left lower abdominal pain and discomfort. Imaging studies, including enhanced abdominal CT and PET-CT, revealed a suspicious mass in the jejunum. Comprehensive diagnostic evaluations excluded metastatic origins, and a diagnosis of primary small intestinal SCC was confirmed by histopathology and immunohistochemistry. The patient underwent radical surgical resection, which revealed a poorly differentiated SCC invading the serosa and regional lymph nodes. Postoperative management included infection prevention and fluid rehydration, with recommendations for adjuvant chemotherapy and immunotherapy based on multidisciplinary consultation. Despite the advanced disease stage, the patient recovered well post-surgery and is undergoing regular follow-up. Conclusion: This case underscores the importance of thorough diagnostic evaluation to distinguish primary SCC from metastatic lesions. Early surgical intervention is critical for improving prognosis of this rare malignancy. The findings contribute to the limited knowledge of the primary SCC of the small intestine and emphasize the need for further research to guide optimal management strategies.

Primary squamous cell carcinoma (SCC) of the renal parenchyma is exceedingly rare, with only seven cases reported to date. We report a 72-year-old woman with recurrent cystitis, gross hematuria, and a right renal mass. Imaging studies revealed a necrotic lesion in the renal parenchyma, initially suggestive of an abscess. Despite percutaneous drainage and antibiotic therapy, there was no clinical improvement. Trans-urinary tract fine-needle aspiration (FNA) provided preoperative cytologic evidence of malignancy with features consistent with SCC, and histopathologic examination of the nephrectomy specimen, supported by immunohistochemistry, confirmed primary renal parenchymal SCC. The patient subsequently underwent radical nephrectomy, and histopathological examination confirmed a primary SCC of the renal parenchyma without renal pelvic involvement. Although surgical treatment was performed promptly, metastatic spread to lymph nodes, vertebrae, and lungs was detected within months, and the patient died 18months postoperatively. This case highlights the importance of considering SCC in the differential diagnosis of abscess-like renal lesions, particularly when they fail to respond to antibiotics. In selected patients, trans-urinary tract FNA offers a rapid, minimally invasive means to obtain cytologic material, which can prevent delays and facilitate timely management, potentially improving outcomes in similarly challenging cases. Additional studies will clarify diagnostic and therapeutic strategies.

Primary squamous cell carcinoma (SCC) of liver is rare, and its prognosis is extremely poor. This study aims at reviewing the clinical data of all pathologically diagnosed liver cancer in our institute, and discussing the clinical presentation, diagnosis, treatment, and prognosis of our cases of SCC and the literatures reported previously.All the patients undergoing liver surgery or biopsy for liver cancers from 2002 to 2013 in our hospital were reviewed, and the liver specimens were examined pathologically. A literature search for case reports of primary SCC of liver published until December 31, 2014, was performed on PubMed, MEDLINE, Scopus Elsevier, Cochrane, and Google Scholar. The primitive data of the case reports were all included and analyzed if available.From January 2002 to October 2013, 2210 cases of liver cancer were diagnosed pathologically in our hospital. Among, 4 cases (0.2%) were diagnosed as primary SCC of liver. All were negative for hepatitis B infection, but present with liver cyst and/or hepatolithiasis. One patient underwent radical resection, but died of tumor recurrence 18 months postoperatively. One patient received transcatheter arterial chemoembolization and 1 patient received laparotomy and alcohol injection, but died 9 and 4 months after surgery, respectively. The last patient received only biopsy and supportive treatment, and finally died of tumor metastasis 6 months later. From 1970 to 2014, 31 cases of primary liver SCC have been published in English previously. Thirty one cases and the 4 cases in the present study were included. The average age of the patients were 54 years (range 18–83), with a male to female ratio of 19:16. Twenty patients had liver cysts, 7 had bile duct stones, and 2 cases had both. Patients undergoing radical surgery had better prognosis than those undergoing palliative treatments (median survival 17 vs 5 months, P = 0.005, log-rank test). Patients with liver cysts seemed to have worse prognosis than those with bile duct stones (median survival 7 vs 18 months, P = 0.090, log-rank test).Primary liver SCC seems to be mostly originated from liver cyst or hepatolithiasis. Radical surgery should be firstly recommended, although the prognosis might be unfavorable.

INTRODUCTION: Pancreatic tumors are typically primary neoplasms, with the majority consisting of ductal adenocarcinomas. Primary squamous cell carcinoma (SCC) of the pancreas is extremely rare, and therefore if found, metastatic disease should be considered. Metastasis to the pancreas is also uncommon with an incidence from 0.7% to 11.1%. Diagnostic evaluation can be challenging as the diagnosis itself can be unreliable based on immunohistochemical staining. We hereby present a case of an esophageal mass found incidentally during workup of a known pancreatic mass, both ultimately proven to be SCC. CASE DESCRIPTION/METHODS: A 64-year old male with past medical history of prior smoking, gastroesophageal reflux disease, esophageal stricture, and prostate cancer presented with 2 months of intermittent periumbilical abdominal pain and nausea. Work-up was noteworthy for CT of the abdomen and pelvis which showed an ill-defined 4.5 × 3.4 cm pancreatic tail mass with peripancreatic stranding, and upper abdominal lymphadenopathy. Serum tumor markers CA 19-9 and CEA were normal. EGD revealed a 2 cm friable, non-obstructing mass in the middle third of the esophagus (Figure 1). On EUS, the mass was noted to invading the muscularis propria. EUS was further notable for a 42 mm by 39 mm hypoechoic mass in the pancreatic tail (Figure 2) and peri-aortic lymphadenopathy. Biopsy and immunohistochemical staining of the esophageal mass, pancreatic mass, and per-aortic lymph nodes are illustrated in Figure 3. The clinical picture was thought to be most likely metastatic SCC of esophageal origin. Palliative chemotherapy with FOLFOX was initiated. DISCUSSION: Primary SCC of the pancreas is extremely rare, and thus requires extensive workup for metastatic disease including CT of the head and chest, upper endoscopy, colonoscopy, pelvic exam with pap smear, and a detailed skin examination. Pancreatic metastasis from another primary site is also rare. Esophageal SCC metastasis to the pancreases is particularly uncommon, with an incidence of 0% to 4.8%. As highlighted by this case, appropriate diagnosis of SCC of a pancreatic mass for treatment guidance remains challenging as metastatic SCC may mimic primary pancreatic malignancy both clinically and cytologically. Therefore, even with tissue diagnosis, primary pancreatic SCC cannot be cytologically distinguished from metastatic SCC through immunohistochemistry and often requires clinical correlation after an extensive workup.Figure 1.: EGD revealed a 2 cm friable, non-obstructing mass in the middle third of the esophagus.Figure 2.: EUS showed a 42 mm by 39 mm hypoechoic mass in the pancreatic tail.Figure 3.: Findings of the biopsies and immunohistochemical staining of the esophageal mass, pancreatic mass, and per-aortic lymph nodes.

Rationale:Primary vaginal squamous cell carcinoma (SCC) is a rare disease. Primary SCC in prolapsed vagina is extremely rare. In the presented case additional bladder involvement was found.Patients concerns:Primary vaginal SCC may be misinterpreted as decubitus in prolapsed vagina and it may delay proper diagnosis and treatment.Diagnoses:Diagnosis was confirmed by the vaginal ulceration biopsy and cystoscopic biopsy of the involved bladder.Interventions:In the case presented percutaneous nephrostomy was the only possible treatment of hydronephrosis.Outcomes:In advanced primary SCC (Figo IVA) with nodal involvement palliative treatment is only option.Lessons:Primary SCC mimicking decubitus which appeared in prolapsed vagina, may be accompanied by bladder involvement.

Primary laryngeal carcinomas comprise approximately 2% to 5% of all malignancies worldwide. Of these laryngeal carcinomas, approximately 99% are primary squamous cell carcinomas. During the past 30 years, about 160 cases of primary small cell carcinoma of the larynx have been reported. Combined primary squamous and small cell carcinoma of the larynx, the so-called composite tumor of the larynx, is even more rare, with only 13 published cases to date. Although the major risk factors for developing these composite tumors of the larynx are thought to be similar to other more common neoplasms of the larynx, such as squamous cell carcinoma, the treatment and prognosis are different. We report an additional case of combined small cell carcinoma of the larynx and discuss the histogenesis of this unusual neoplasm.