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Simple Summary: There have been no analyses of tumor budding (TB) in different margin sections and using the fixation method in HNSCC in the literature. The mean TB (TB rel) of all tumor-positive margin sections (n = 443) of the primary tumor was analyzed in an FFPE-fixed tumor from 66 patients with HNSCC, and they were compared with cryo-fixed sections. TB rel correlates significantly with tumor aggressiveness. TB often varies between the different tumor margins of FFPE sections of the same patient, and they differ depending on the fixation method. Our data show that a randomly selected margin section does not reliably reflect the TB, and thus, it cannot predict the prognostic outcome. TB rel could compensate for the differences in TB score analysis. The determination of the TB score in cryo sections seems to be inaccurate compared with analyses in FFPE. The method shown here is cost effective, easy to integrate into a clinical workflow, and seems useful for future studies. Background: Tumor budding (TB) is a histomorphological characteristic of the tumor invasion front and it has an impact on the tumor outcome prediction for head and neck squamous cell carcinoma (HNSCC) aetiopathology. Patients and methods: The average TB score (TB rel) of all tumor-positive marginal sections (n = 443) in the primary tumor was analyzed in the FFPE-fixed tumor slices of 66 patients with HNSCC, and they were compared with cryo-fixed sections. Results: TB rel correlates with tumor aggressiveness (i.e., lymph node metastasis quantity, lymph node ratio, extra capsular growth, Pn1, pV1, grading). The TB scores often vary between the different tumor margins of FFPE sections in the same patient, and in many cases, they differ depending on the fixation method. Conclusion: Our data show that a randomly selected marginal cut cannot reliably mirror the TB score, and thus, they cannot predict the prognostic outcome. However, TB rel could be a tool that compensates for differences in TB score analysis. TB score determination in cryo sections seems to be inaccurate compared with TB determination in FFPE. [ABSTRACT FROM AUTHOR]

Background: The spread of cervical squamous cell carcinoma to the inner surface of the uterus with replacement of the endometrium is rare. Continuity of the lesion must be demonstrated to confirm superficial spread and rule out concomitant endometrial cancer.Case Presentation: We present the case of a 66-year-old white woman with superficial spreading squamous cell carcinoma of the cervix that involved the endometrium. Her relevant past history included conization of the cervix to treat cervical intraepithelial neoplasia III with positive margins. She subsequently had three negative cervical vaginal cytology results, each with a positive high-risk human papillomavirus test. Transvaginal ultrasound showed occupation of the entire uterine cavity by dense material consistent with pyometra in addition to myometrial thinning due to tension and cervical dilation. The patient presented with greenish vaginal discharge of 3 months' duration. The cervix was not visible during speculum examination. Access for endometrial sampling was not possible, raising suspicion of post-conization cervical stenosis. The patient was treated with laparoscopic hysterectomy with double adnexectomy. Histologic examination showed superficial squamous cell carcinoma invading the cervix to a depth of 2.8 mm; superficial spreading squamous cell carcinoma in situ was also observed in the lower uterine segment and endometrium. The patient was free of symptoms 12 months after surgery.Conclusions: Squamous cell carcinoma of the cervix with superficial spread to the endometrium is not included in the 2020 (fifth edition) World Health Organization Classification of Female Genital Tract Tumors or the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system. More clinical cases are needed to identify other prognostic factors and inform clinical practice guidelines on the management of this disease. [ABSTRACT FROM AUTHOR]

Although the most common gynecologic tumor of the female genital system is endometrial adenocarcinoma, endometrial squamous cell carcinoma (ESCC) is rarely seen. The presence of ESCC is commonly known as a concomitant tumor secondary to cervical squamous cell carcinoma (SCC). However primary endometrial squamous cell carcinoma (PESCC) is a more rare tumor type. In situ carcinoma, defined as the inflammation of entire intraepithelial tissue with dysplastic cells without identifying any concomitant invasion or metastasis, is considered to be among the precancerous lesions of the female genital system. In situ squamous cell carcinoma cases, especially identified in the cervical region, can be rarely observed in the endometrial tissue. In this case report, the authors aimed to discuss a case of cervical and ESCC in situ which is reported for the first time in the literature. [ABSTRACT FROM AUTHOR]

The coexistence of cervical and endometrial surface squamous cell carcinoma (SCC) is extremely rare. A 63-year-old woman was referred to the present hospital because of an abnormal Pap smear indicating SCC. Biopsies from the vagina, ectocervix, and endocervix indicated SCC in situ, and endometrial curettage revealed SCC with stromal invasion. The patient underwent a radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Microscopically, the SCC in situ exhibited extensive spread into the vagina, uterine cervix, endometrium, bilateral fallopian tubes, and left ovary. In addition, extensive stromal invasion into the uterine corpus was identified. Polymerase chain reaction revealed human papilloma virus (HPV) type 16 from biopsies from the uterine cervix, corpus, and vagina. SCC of the endometrium may arise secondarily to HPV infection and may spread, in some cases, superficially into the vagina, cervix, and adnexal organs. Additional studies are required to fully elucidate the precise mechanisms of carcinogenesis and tumor spreading in endometrial SCC. [ABSTRACT FROM AUTHOR]

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Humoral hypercalcemia of malignancy ( HHM) is a paraneoplastic syndrome primarily caused by a tumor-producing parathyroid hormone-related protein ( PTH- rP). We describe the first reported case of a uterine carcinosarcoma causing HHM. A 70-year-old patient was transferred to our hospital for a uterine tumor accompanied by impaired consciousness. The laboratory tests indicated anemia, malnutrition, elevated serum calcium and elevated PTH- rP. Emergency surgery, including abdominal hysterectomy and bilateral salpingo-oophorectomy, was performed due to uncontrollable uterine bleeding. The pathological diagnosis was carcinosarcoma consisting of pure squamous cell carcinoma in its epithelial component. Postoperatively, chemotherapy with paclitaxel and carboplatin was performed. The patient had recurrent tumors at the para-aortic lymph nodes 11 months after the initial surgery and underwent a pelvic and para-aortic lymphadenectomy, which removed all of the recurrent tumors. [ABSTRACT FROM AUTHOR]

Background: Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. Methods: We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. Results: All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. Conclusions: Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract. [ABSTRACT FROM AUTHOR]

Background: Seborrheic keratosis is a common, benign skin tumor. Numerous reports have shown its possibility of malignant transformation. This study was designed to demonstrate the occurrence of concomitant seborrheic keratosis and skin cancers. Materials and Methods: Data was retrospectively reviewed from all patients with a diagnosis of seborrheic keratosis in pathology department of Alzahra Hospital and a private pathology laboratory in Isfahan, Iran over a 4-year period. We classified all demographic data and associated dysplasia or Bowen's disease and analyzed them by student-t or chi-square tests. Results: From all 429 specimens, 5 (1.2%) were found to be associated with Bowen's disease and one (0.2%) with mild dysplasia in squamous epithelium. All cases arose within the clinically, atypical seborrheic keratosis. More men were affected with lesions alone and with malignancy (230/423 (54.4%) and 5/6 (83.3%), respectively) compared to women. The average age of patients suffering from lesions with and without associated malignancy was 57 and 54 years, respectively. The common site of lesion alone was head and neck but lesions with malignancy involved lower extremities. The two lesions were significantly different in site of occurrence (p < 0.001). Conclusion: Generally, although the association between seborrheic keratosis and skin malignancy appears to be accidental, it must always be in mind. Therefore, histopathologic examination of all seborrheic keratosis should be considered, especially when seborrheic keratosis has atypical clinical manifestations. [ABSTRACT FROM AUTHOR]

Primary squamous cell carcinoma of the endometrium (PESCC) is rare and its pathogenesis is unclear. Identification of PESCC and its differentiation from endometrial involvement by squamous cell carcinoma is essential for correct patient management and is based on strict pathological criteria. We present a case of a 71-year-old patient satisfying the proposed diagnostic criteria for PESCC together with a review of the literature. [ABSTRACT FROM AUTHOR]

Purpose: Primary endometrial squamous cell carcinoma (ESCC) are rare but aggressive malignancies. To evaluate therapeutically relevant molecules, ESCC were investigated immunohistochemically. Material and methods: Eight ESCC were stained with antibodies against estrogen and progesterone receptors, HER-2/neu, and COX-2 followed by semiquantitative evaluation of the staining results. Results: Seven out of eight ESCC were negative for estrogen receptor as well as for HER-2/neu. Four tumors showed positivity for progesterone receptor. All ESCC displayed COX-2 overexpression. Conclusions: Primary ESCC are probably not under hormonal control of estrogens and lack HER-2/neu expression. Thus, anti-hormonal or antibody therapy with herceptine is not indicated. The use of COX-2 inhibitores might be a therapeutic alternative in ESCC that requires further investigation. [ABSTRACT FROM AUTHOR]

Background. Primary squamous cell carcinoma of the endometrium is exceedingly rare. It has been described in association with pyometra but its etiology is still unclear.: CaseThe authors report the case of a 75-year-old woman who presented with pelvic pain and pyometra. No gross tumor was identified in the uterus; however, extensive epidermalization of the endometrial mucosa was noted. Microscopic findings were consistent with a primary in situ squamous carcinoma of the endometrium associated with extensive squamous metaplasia and areas of dysplasia. HPV antigen and DNA detection were negative in both the endometrial lesions and the cervix.: ConclusionsThese results support the sequence of change with squamous metaplasia, progressing through dysplasia to carcinoma as a possible pathogenetic process. HPV’s role, however, remains uncertain. [Copyright &y& Elsevier]