Low Molecular Weight Cytokeratin Research Articles

Cytokeratin 13 (CK13) expression in cancer: a tissue microarray study on 10,439 tumors.

Cytokeratin 13 (CK13) is a type I acidic low molecular weight cytokeratin, which is mainly expressed in urothelium and in the squamous epithelium of various sites of origin. Loss of CK13 has been implicated in the development and progression of squamous epithelial neoplasms. To comprehensively determine CK13 expression in normal and neoplastic tissues, a tissue microarray containing 10,439 samples from 131 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. CK13 immunostaining was detectable in 42 (32.1%) of the 131 tumor categories including 24 (18.3%) tumor types with at least one strongly positive case. The highest rate of positive staining was found in various urothelial neoplasms (52.1-92.3%) including Brenner tumor of the ovary (86.8%) and in squamous cell carcinomas from various sites of origin (39.1-77.6%), Warthin tumors of parotid glands (66.7%), adenosquamous carcinomas of the cervix (33.3%), thymomas (16.0%), and endometroid carcinomas of the ovary (15.3%). Twenty other epithelial or germ cell neoplasms showed - a usually weak - CK13 positivity in less than 15% of the cases. In bladder cancer, reduced CK13 expression was linked to high grade and advanced stage (p < 0.0001 each). In squamous cell carcinoma of the cervix, reduced CK13 immunostaining was related to high grade (p=0.0295) and shortened recurrence-free (p=0.0094) and overall survival (p=0.0274). In a combined analysis of 1,151 squamous cell carcinomas from 11 different sites of origin, reduced CK13 staining was linked to high grade (p=0.0050). Our data provide a comprehensive overview on CK13 expression in normal and neoplastic human tissues. CK13 expression predominates in urothelial neoplasms and in squamous cell carcinomas of different organs, and a loss of CK13 expression is associated with aggressive disease in these tumors.

Cytokeratin 10 (CK10) expression in cancer: A tissue microarray study on 11,021 tumors

Cytokeratin 10 (CK10) is a type I acidic low molecular weight cytokeratin which is mainly expressed in keratinizing squamous epithelium of the skin. Variable levels of CK10 protein have been described in squamous carcinomas of different sites and in some other epithelial neoplasms. To comprehensively determine the prevalence of CK10 expression in normal and neoplastic tissues, a tissue microarray containing 11,021 samples from 131 different tumor types and subtypes was analyzed by immunohistochemistry. CK10 immunostaining was detectable in 41 (31.3 %) of 131 tumor categories, including 18 (13.7 %) tumor types with at least one strongly positive case. The highest rate of positive staining was found in squamous cell carcinomas from various sites of origin (positive in 18.6 %–66.1 %) and in Warthin tumors of salivary glands (47.8 %), followed by various tumor entities known to potentially exhibit areas with squamous cell differentiation such as teratomas (33.3 %), basal cell carcinomas of the skin (14.3 %), adenosquamous carcinomas of the cervix (11.1 %), and several categories of urothelial neoplasms (3.1 %–16.8 %). In a combined analysis of 956 squamous cell carcinomas from 11 different sites of origin, reduced CK10 staining was linked to high grade (p < 0.0001) and advanced stage (p = 0.0015) but unrelated to HPV infection. However, CK10 staining was not statistically related to grade (p = 0.1509) and recurrence-free (p = 0.5247) or overall survival (p = 0.5082) in 176 cervical squamous cell carcinomas. In the urinary bladder, CK10 staining occurred more commonly in muscle-invasive (17.7 %) than in non-invasive urothelial carcinomas (4.0 %–6.0 %; p < 0.0001). In summary, our data corroborate a role of CK10 as a suitable marker for mature, keratinizing squamous cell differentiation in epithelial tissues. CK10 immunohistochemistry may thus be instrumental for a more objective evaluation of the clinical significance of focal squamous differentiation in cancer.

Malignant Glomus Tumor of the Kidney: A Case Report and Review of the Literature

Abstract Introduction/Objective Glomus tumors are rare neoplasms arising from the glomus body which is a specialized arteriovenous anastomosis that has a role in temperature regulation of the skin. They account for less than 2% of soft tissue tumors and typically manifest as painful nodules in the extremities, most commonly in the subungual region of the fingers and dermis of the wrist, forearm, and foot. They rarely arise in visceral organs as they lack glomus bodies. There are rare case reports of benign glomus tumors arising in the kidney, and malignant renal glomus tumors are exceedingly rare. Methods/Case Report We present a case of a 32-year-old man who was found to have a right renal mass incidentally after being involved in a motor vehicle accident. Computed tomography of the abdomen revealed a 5.3 cm enhancing mass in the posterior aspect of the inferior pole of the right kidney. Histological examination revealed a solid neoplasm composed of a pleomorphic population of cells with densely eosinophilic to pale cytoplasm, centrally located round to oval nuclei with fine nuclear chromatin and relatively inconspicuous nucleoli. Prominent lymphovascular invasion and 1 mitotic figure per 10 high power fields were also present. Areas composed of necrosis, sclerosis, hemosiderin deposition and calcification were identified. Immunohistochemical stains revealed the neoplastic cells to be positive for CD34, vimentin, smooth muscle actin, caldesmon, with focal reticulin staining around the tumor cells. Cells were negative for desmin, high and low molecular weight cytokeratins, synaptophysin, chromogranin, PAX8, and GATA3. The morphology and immunoprofile of the mass are consistent with the diagnosis of glomus tumor. Results (if a Case Study enter NA) NA Conclusion Although very rare, the presence of prominent vascular invasion, increased mitotic activity as well as necrosis are consistent with malignant behavior and support the classification as a malignant glomus tumor.

Low Molecular Weight Cytokeratin Immunohistochemistry Reveals That Most Salivary Gland Warthin Tumors and Lymphadenomas Arise in Intraparotid Lymph Nodes

The nature of the lymphoid stromal component in Warthin tumor and lymphadenoma of the parotid gland has been a controversial topic in salivary gland pathology for decades. Two theories exist: first, that these tumors arise from salivary gland inclusions within intraparotid lymph nodes; and second, that they arise within salivary gland parenchyma and induce tumor-associated lymphoid proliferation (TALP). A recent study demonstrated that low molecular weight cytokeratin is effective in distinguishing salivary gland tumors within lymph nodes from those inducing TALP via identification of extrafollicular reticulum cells, which are only found in true lymph nodes. Twenty-one Warthin tumors and 4 lymphadenomas were retrieved from the archives of the Department of Pathology at University of Texas Southwestern Medical Center.Cam5.2 immunohistochemistry was performed on each case and independently evaluated by two pathologists. Extrafollicular reticulum cells were identified by Cam5.2 immunostaining in 21 of 21 Warthin tumors (100%), and 3 of 4 lymphadenomas (75%). Extrafollicular reticulum cells were consistently localized to the perisinusoidal and paracortical areas of the lesions studied. Extrafollicular reticulum cells were identified via low molecular weight cytokeratin Cam5.2 immunohistochemistry in all of the Warthin tumors and most of the lymphadenomas evaluated.This finding strongly supports the notion that these most if not all of these tumors arise within intraparotid lymph nodes, presumably from salivary gland inclusions entrapped during embryonic development.

Low Molecular Weight Cytokeratin Immunostaining for Extrafollicular Reticulum Cells is an Effective Means of Separating Salivary Gland Tumor-Associated Lymphoid Proliferation from True Lymph Node Involvement

Tumor-associated lymphoid proliferation (TALP) is a well-recognized lymphocytic reaction that is commonly associated with certain salivary gland tumors. A salivary carcinoma with TALP may be confused for true lymph node involvement by that tumor, constituting a potential pitfall in tumor staging that may result in unnecessary therapeutic intervention or erroneous prognostication for patients. True lymph nodes harbor populations of extrafollicular reticulum cells (ERCs), which can be highlighted by low molecular weight cytokeratin immunohistochemistry. We sought to determine whether low molecular weightcytokeratin Cam5.2 immunostaining may be utilized to differentiate true lymph node involvement by salivary gland tumors from TALP. The surgical pathology archives of the University of Texas Southwestern Medical Center was searched forcases of salivary gland neoplasms exhibiting either TALP or true lymph node involvement. Hematoxylin and eosin-stained sections were examined. Cases were classified on the basis of a definitive lymph node capsule and subcapsular sinus, as seen on routine histologic evaluation. Low molecular weight cytokeratin Cam5.2 immunostaining was performed and evaluated on all cases. Twenty-three salivary gland carcinomas with TALP and 16 carcinomas involving a lymph node (14 carcinomas metastatic to regional lymph nodes and 2 carcinomas arising from benign lymph node inclusions) were identified. Numerous Cam5.2-positive ERCs were identified within the nodal tissue of all true lymph nodes involved by carcinoma (16 of 16 cases), while Cam5.2-positive ERCs were completely absent in all cases of salivary gland lesions with TALP (0 of 23 cases) (100% vs. 0%, p < .0001, Fisher's Exact). Utilization of low molecular weight cytokeratin Cam 5.2 immunostaining for ERCs is a highly useful tool for distinguishing true lymph node involvement by salivary gland carcinomas from TALP. This strategy may be useful in identifying genuine nodal metastasis in histologically ambiguous cases, and to avoid erroneously upstaging tumor with TALP as nodal metastasis with the resulting prognostic and therapeutic implications. Moreover, low molecular weight cytokeratin immunostaining may be useful in confirming the rare examples of salivary gland tumors arising from intranodal salivary gland inclusions.

GATA3 immunoreactivity expands the transcription factor profile of pituitary neuroendocrine tumors

The modern classification of pituitary neuroendocrine tumors relies mainly on immunohistochemistry for pituitary transcription factors, hormones, and other biomarkers, including low molecular weight cytokeratins. The transcription factor GATA2 is required for development of gonadotrophs and thyrotrophs but has not been used for classification of pituitary tumors. Because of genomic paralogy of GATA2 and GATA3, we postulated that GATA3 immunohistochemistry may detect GATA2 in the adenohypophysis. We examined 151 tumors originating from Ondokuz Mayis University, Turkey (n = 83) and University Health Network, Canada (n = 68). Initially, 83 tumors (26 gonadotroph, 24 somatotroph, 17 corticotroph, 12 lactotroph, 2 poorly differentiated Pit-1 lineage tumors that expressed TSH and 2 null cell tumors) from Ondokuz Mayis University were investigated with the GATA3 monoclonal antibody L50-823. Retrospective review of the files of University Health Network identified 68 tumors (43 gonadotroph, 3 somatotroph, 2 lactotroph, 1 mammosomatotroph, 9 corticotroph, 7 poorly differentiated Pit-1 lineage tumors with TSH expression, 2 plurihormonal tumors with TSH expression and 1 null cell tumor) that were examined with the same GATA3 antibody and served as a validation cohort. All somatotroph, lactotroph and mammosomatotroph tumors and the null cell tumors were negative for GATA3. Sixty-eight (98.5%) gonadotroph tumors were positive for GATA3; 64 had diffuse reactivity. Two plurihormonal tumors with TSH expression and eight (88.8%) poorly differentiated Pit-1 lineage tumors with variable TSH expression were positive for GATA3. One of 26 (3.8%) corticotroph tumors was diffusely positive for GATA3. This study shows that GATA3 immunoreactivity is characteristic of pituitary gonadotroph and TSH-producing tumors. This finding expands the pattern of transcription factors that are used to classify adenohypophysial tumors and is important in the differential diagnosis of sellar tumors, as GATA3 expression is also a feature of primary sellar paragangliomas as well as carcinomas that may metastasize to the sella.

Spatial Mapping of Myeloid Cells and Macrophages by Multiplexed Tissue Staining.

An array of phenotypically diverse myeloid cells and macrophages (MC&M) resides in the tumor microenvironment, requiring multiplexed detection systems for visualization. Here we report an automated, multiplexed staining approach, named PLEXODY, that consists of five MC&M-related fluorescently-tagged antibodies (anti - CD68, - CD163, - CD206, - CD11b, and - CD11c), and three chromogenic antibodies, reactive with high- and low-molecular weight cytokeratins and CD3, highlighting tumor regions, benign glands and T cells. The staining prototype and image analysis methods which include a pixel/area-based quantification were developed using tissues from inflamed colon and tonsil and revealed a unique tissue-specific composition of 14 MC&M-associated pixel classes. As a proof-of-principle, PLEXODY was applied to three cases of pancreatic, prostate and renal cancers. Across digital images from these cancer types we observed 10 MC&M-associated pixel classes at frequencies greater than 3%. Cases revealed higher frequencies of single positive compared to multi-color pixels and a high abundance of CD68+/CD163+ and CD68+/CD163+/CD206+ pixels. Significantly more CD68+ and CD163+ vs. CD11b+ and CD11c+ pixels were in direct contact with tumor cells and T cells. While the greatest percentage (~70%) of CD68+ and CD163+ pixels was 0–20 microns away from tumor and T cell borders, CD11b+ and CD11c+ pixels were detected up to 240 microns away from tumor/T cell masks. Together, these data demonstrate significant differences in densities and spatial organization of MC&M-associated pixel classes, but surprising similarities between the three cancer types.

Primary Cutaneous Adenoid Cystic Carcinoma Connecting to the Epidermis

Primary Cutaneous Adenoid Cystic Carcinoma Connecting to the Epidermis

EXPRESSION OF MMP-9 AS A PROGNOSTIC FACTOR OF UTERINE SARCOMA

Uterine sarcoma is a highly aggressive mesenchymal neoplasm with an extremely unfavorable prognosis. Up today there are still relevant issues concerning search for clinical-morphological and biomolecular criteria for prognosis relapse-free survival of uterine sarcoma patients. It is well-known, the increase of the expression level of MMP-9 in primary tumor or metastatic foci correlates with a low differentiation of tumor cells, high ability for invasiveness, high metastatic activity, and shortened life expectancy. It’s still unknown, whether it is possible to consider the expression of MMP-9 in uterine sarcoma cells as a convincing prognostic factor. For many types of epithelial malignant neoplasms, high metastatic rate is associated with an increase level of MMP-9 both in plasma and in tumor tissue. The purpose of this study is to investigate the features of MMP-9 expression in uterine sarcoma cells for development of the model for individual prediction of the disease course. The study of the surgical material of selected 54 cases of uterine sarcoma of stage I-II (according to FIGO criteria) with a known prognosis of the disease, which were distributed depending on the morphological type done: leiomyosarcoma (LMS) – 18 cases, endometrial stromal sarcoma (ESS) - 22 cases, undifferentiated sarcoma (US) – 14 (according to the classification of tumors of the uterus of the WHO). For histological examination, pieces of tissue were cut from different parts of the tumor nodes – central, peripheral, parts of the adjacent intact tissue of myometrium (total of 6-8 bits). The tumor cell phenotype was determined using low molecular weight cytokeratins (Cytokeratin PAN, AE1 / AE3), smooth muscle actin (Smooth Muscle Actin, 1A4), myogenin (Myogenin (F5D)), CD 10 and vimentin (Vimentin, V9). The histochemical label was evaluated in two parameters: the degree of prevalence and intensity of coloration. To assess the color intensity, a qualitative scale was used: 0 – no reaction, 1+ – weak cytoplasmic coloration to 30.0% of tumor cells, 2+ – moderate reaction, 30.0 to 60.0% of stained cells, 3+ – pronounced cytoplasmic reaction in 60,0-100,0% of tumor cells. Statistical processing of the data was performed using the “STATISTICA 10.0” program package. The conducted study has showed, the negative (0) and weak (1+) expression of matrix metalloproteinase-9 were observed in the most part of ESS and only partially in US. Despite the stage of the disease, with such a status of MMP-9, there was observed no signs of relapsed disease. The moderate (2+) and high (3+) expression of MMP-9 was detected in 44.5 % of uterine sarcoma, in the most part in LMS patients. However, if in LMS cases the progressive disease was observed only in one third of them (4 of 12 cases), in case of ESS and US, in all the patients with such tumors status there was observed relapsed disease. Such a reaction may be indicative for invasive and metastatic potential of ESS and US and cause of the hematogenous metastases.

Study of Merkel cells in the dog through the immunohistochemical expression of five different commercial antibodies: comparative analysis

ABSTRACTMerkel cells (MCs) are cutaneous specialized cells with a wide immunohistochemical profile, including low molecular weight cytokeratins and various endocrine and neural markers. Differences in expression of these markers may be a consequence of contradictory results in studies of MCs in normal and damaged canine tissues. The present study aimed to compare five different commercial available antibodies developed against cytokeratins 8 + 18 and 20, neuron-specific enolase, chromogranin A, and synaptophysin on formalin-fixed paraffin-embedded samples of hard palate, cheek skin including sinus hair follicles or vibrissae, nasal planum, and footpads. The antibodies showed great variability with respect to quality and intensity of immunoreactivity to identify MCs. Anti-Cytokeratin 20 antibody is more effective to recognize MCs in the dog skin followed by the antibodies against neuron-specific enolase, cytokeratins 8 and18, chromogranin A, and synaptophysin. There was also a significant difference in intensity of immunoreaction scores between them depending on the location examined. These results represent a necessary basic background for future studies of the role of these cells in normal and damaged canine tissues.

Uterine Cervix Metastasis of Myxopapillary Ependymoma Originated from the Spinal Cord.

Myxopapillary ependymomas are well differentiated low-grade tumors which have been documented to local or distant metastasis. In the literature, this is a unique case of myxopapillary ependymoma with metastasis to the uterine cervix. Here, we present a rare case of extra neural metastasis of spinal ependymoma that developed over a long period. A 34-year-old woman was referred to our hospital for pelvic mass. A mass (110×100 mm) localized between the sacrococcygeal region and the uterus was detected by magnetic resonance imaging. In 2004, she had been operated upon for myxopapillary ependymoma seated in the sacrococcygeal region for the first time. She underwent tumor resection eight times due to the recurrence of spinal tumor in the same region in nine years. Under the diagnosis of uterine neoplasm, we carried out radical hysterectomy, omentectomy and pelvic lymphadenectomy as the surgical procedure. The pathological findings were reported as myxopapillary ependymoma. Immunohistochemically, the myxopapillary ependymal cells showed strong positivity for glial fibrillary acidic protein, whereas they were negative for low molecular weight cytokeratin. The Ki-67 labeling index was about 2-3%. The patient had an uneventful postoperative period. She has remained free of symptoms in the year since surgery. Extra-spinal myxopapillary ependymoma is very rare, but it must be considered in the differential diagnosis of pelvic mass lesions.

Eccrine porocarcinoma in the face

Investigations Her chest X-ray, complete blood count, renal and liver function tests were all normal. Excisional skin biopsy showed a circumscribed nodular growth in the dermis, composing of anastomising nests and cords of cells separated by fibrous stroma (Figure 2). Focal glandular differentiation with ductal structure was noted. The tumor cell nuclei were round to oval, with coarse chromatin, and small but distinct nucleoli. Mitotic figures were frequently seen. Moderate nuclear atypia and high nucleo-cytoplasmic ratio were noted in places. No perineural or vascular invasion was seen. The overlying epidermis was not involved. The tumor Date: 13 January 1999 Venue: Yaumatei Skin Center Organizer: Social Hygiene Service, DH; Clinico-pathological Seminar extended fairly close to the deep resection margin. Immuno-histochemical studies showed that the tumor cells were positive for CAM5.2 (low molecular weight cytokeratin) and the ductal structure was highlighted by carcinoembryonic antigen (CEA) and AE1/AE3 (high molecular weight cytokeratin) stains. The histopathology was that of eccrine porocarcinoma.

Primary Ewing's sarcoma of the sinonasal tract, eroding the ethmoid and sphenoid sinus with intracranial extension: A rare case report.

Ewing's sarcoma (ES) is an aggressive tumour that may present with skeletal and extraskeletal forms. The extraskeletal form is rarely encountered in the head and neck region and is extremely rare in the sinonasal tract. This is the case report of a ES of the ethmoid sinus with intracranial and orbital extension in a 33-year-old male patient who presented with anosmia, epistaxis, reduction of visual acuity in the left eye and headache. On otorhinolaryngological clinical examination and biopsy via flexible endoscope, the lesion was misdiagnosed as ethmoid sinus carcinoma. The subsequent magnetic resonance imaging (MRI) of the brain revealed a large mass (6×7 cm) eroding the ethmoid and sphenoid sinuses, extending beyond the orbits and occupying the anterior cranial fossa with a maximum extension of ~5 cm. The patient underwent surgical resection and the microscopic examination of the specimen established the diagnosis of ES (immunohistochemically positive for CD99, neuron-specific enolase, CD56, synaptophysin, pancytokeratin, low-molecular weight cytokeratins and vimentin. The periodic acid Schiff stain exhibited strong intracytoplasmic block positivity and fluorescence in situ hybridization revealed a t(22;11) translocation. First-line chemotherapy was administered for 3 cycles; however, on restaging MRI, local disease progression was diagnosed. The patient received radiotherapy and second-line chemotherapy for 6 cycles. At 15 months after the diagnosis, the patient remains recurrence-free and maintains a good functional status and quality of life.

Neuroendocrine Carcinoma of the Mammary Gland in a Dog

A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland.

Tissue Expression of Low and High Molecular Weight Cytokeratins in Lung Carcinoma Sections: Its Correlation with Some Clinic-Pathological Features

The tissue expression of low (LMW) and high (HMW) molecular weight cytokeratins and Ber-EP4 antigen in both small (SCLC) and non-small (NSCLC) cell lung carcinomas, as well as its correlation with a variety of clinic-pathological features, was evaluated. In general, 43/52 (82.7%) of NSCLC sections showed the expression of at least one type of cytokeratin while only 7/16 (43.7%) of SCLC were stained with both LMW cytokeratin and pan-cytokeratins antibodies. Remarkably, 18/52 (34.6%) of NSCLC were positive to both types of cytokeratins. However, none of SCLC showed this pattern of expression. In NSCLC patients, the increasing levels of HMW cytokeratins expression, as shown by 34βE12 antibody, correlated with the occurrence of disease recurrence (P=0.0057; Fisher’s exact test). Consequently, the expression of HMW cytokeratins was found to be associated with a poor 4-year overall survival of NSCLC patients (P=0.0315; Log rank test), not taking into account the histopathological classification of tumors. Similar results were obtained when 8-year overall survival was assessed (P=0.0103; Log rank test). Our results could suggest the assessment of HMW cytokeratins in a larger series of NSCLC samples in order to confirm the potential prognostic value of them.

Procurement and cytological features of human fallopian tube fimbrial cells by ex vivo imprinting and washing

Fallopian tube intraepithelial cancer is a postulated precursor of epithelial ovarian carcinomas. As research continues on epithelial ovarian carcinomas' developmental pathways, representative tubal tissue must be procured for diagnostic, biological, and molecular studies without compromising pathological diagnosis. Fallopian tube fimbrial epithelia were harvested from postmenopausal women undergoing surgery for non-neoplastic gynecologic lesions (n = 16) and epithelial ovarian carcinomas (n= 6). Cytological imprints and washings were obtained from each fimbria and stained by Diff-Quik and rapid Papanicolaou for general cytomorphology; by Trypan blue for cell viability; and by rapid immunohistochemistry for evaluation of low molecular weight cytokeratin, MIB-1, p53, and high-mobility group A (HMGA2) expression. Benign and malignant tubal imprints harvests yielded means of 3.5 × 105 and 1.2 × 106 cells/fimbria, respectively, with viabilities higher than 85%. A mean of 2.5 × 105 cells/fimbria was obtained from fimbrial washings. The mean DNA, RNA, and protein contents of benign imprints were 2.4, 1.5, and 67 μg/fimbria, respectively. Benign cell populations contained nearly 97% cytokeratin-positive and p53/HMGA2-negative cells, which were dispersed within a watery to proteinaceous material and rare microcalcifications. Fimbrial imprints from serous carcinomas involving the fimbriae exhibited abnormal p53 and HMGA2 expression, high proliferation, and diagnostic criteria of malignancy, including prominent nucleoli and cell crowding. Exvivo harvest from operative specimens allows for collection of cell populations representative of native fimbrial epithelium and free of significant contaminants. Tubal harvest facilitates triaging of cellular material for basic, clinical, and translational studies on cancer pathobiology and also represents a potential diagnostic adjunct to emerging invivo high-resolution optical technologies.

Benign fibrous histiocytoma of the ethmoids in an infant

We performed an immunohistochemical and ultrastructural study on 67 specimens of malignant fibrous histiocytoma (MFH) from 65 patients. Most of the tumors were musculoskeletal in origin and all presented clinically as a primary malignancy. The tumors were high grade and 57 of 67 were the storiform-pleomorphic subtype. Immunohistochemical studies were performed in 34 cases with both fresh-frozen and formalin-fixed tissue; in 33 cases only formalin-fixed tissue was available. The immunohistochemical panel included vimentin, various molecular weight keratins, epithelial membrane antigen (EMA), desmin, α-1-antitrypsin, and α-1-antichymotrypsin. Seventeen of 67 (25.4%) cases stained with one or more keratin antibodies. The low molecular weight cytokeratins demonstrated the most widespread and intense staining and, using fresh-frozen tissue, increased sensitivity. Epithelial membrane antigen was detected in 20.6% of cases and six of these cases also stained with keratin. The EMA staining was more focal and less intense than the keratin reactivity. The keratin- or EMA-positive cases were not distinguished by their light microscopic or ultrastructural features. Desmin staining was focally present in 16.9% of cases. The vast majority of tumors stained with vimentin and α-1-antitrypsin or α-1-antichymotrypsin. There was no staining of tumor cells for S-100. Appropriately fixed tissue was available for electron microscopic evaluation in 15 of 23 MFHs that stained with keratin or EMA. Ultrastructurally, all tumors were composed of an admixture of cells that had the features of fibroblasts, myofibroblasts, and histiocytes; no epithelial structures were identified. This study confirms that MFH may express epithelial markers. It emphasizes the importance of using electron microscopy and clinical findings to distinguish keratin or EMA-positive MFH from carcinoma. This distinction is important because of the significant differences in therapy and prognosis.

Adrenocortical carcinoma: a comprehensive immunohistochemical study of 40 cases.

Adrenocortical carcinomas (ACC) are uncommon tumors of the adrenal cortex that are known to follow an aggressive clinical course. The distinction of these tumors from other neoplasms may sometimes prove difficult due to overlapping clinical, morphologic, and even immunophenotypical features. To this end, we performed a comprehensive immunohistochemical analysis using traditional and novel markers in 40 cases of ACC. An immunohistochemical panel consisting of 10 traditional and novel antibodies was applied to whole tissue sections of ACC including high-molecular weight cytokeratin (HMWCK), low-molecular weight cytokeratin (CAM5.2), inhibin-α, melan A, chromogranin A, synaptophysin, calretinin, steroid receptor coactivator-1 (SRC-1), Pax8, and Ki67. The percentage of positive tumor cells as well as the intensity of staining were evaluated and scored; for Ki67 the percentage of positive tumor cells was recorded. Positive staining was observed for SRC-1 (39/40; 97.5%), inhibin-α (37/40; 92.5%), calretinin (32/40; 80%), synaptophysin (29/40; 72.5%), melan A (26/40; 65%), and CAM5.2 (9/40; 22.5%). Rare cases showed positivity for chromogranin A (2/40; 5%) and Pax8 (1/40; 2.5%). None of the cases showed any reactivity with HMWCK. The Ki67 index ranged from <5% to 20%. We conclude that there is no single specific marker to reliably distinguish ACC from other primary or metastatic neoplasms. However, a combination of immunohistochemical stains in a panel consisting of SRC-1, inhibin-α, calretinin, and HMWCK may be of aid in the differential diagnosis of these tumors. In addition, Pax8 is only rarely positive in ACC, which is a useful tool in their separation from renal neoplasms.

Ugly is not only skin deep: A case of osteogenic melanoma.

e20009 Background: Although the incidence of malignant melanoma is high, the incidence of metaplastic malignant melanoma is low. Within the various subtypes of malignant metaplastic melanoma, the manifestation of osteogenic melanoma remains a rarer event. Current review of the literature reveals only 12 reported cases. Of these reported cases, scant discussion is made on treatment whereas the histopathology is discussed in great detail. Methods: We present the case of a 64 year old Caucasian man that was diagnosed with synchronous tumors of the foot and lung. Initial biopsy of the foot revealed metastatic osteogenic melanoma. As a result of the initial biopsy results and imaging, the patient underwent a right lower lobe resection and lymph node dissection followed by a left lower extremity Pirigoff’s amputation and inguinal lymph node dissection. Results: Immunohistochemical staining of the extirpated tissue from the lung revealed strong reactivity to S100, vimentin, Sox10, diffuse reactivity to low molecular weight cytokeratin and HMB-45/MART-1 and no lymph node involvement. Whereas the IHC of the extirpated tissue of the left foot remained consistent with the initial biopsy of strong reactivity to S100 and MART-1 and negative to pancytokeratins, CD34, Desmin, and SMA. Conclusions: Given the features of the patient’s pathology and resected metastatic disease, he was administered adjuvant alpha interferon therapy.

Sclerosing odontogenic carcinoma – an enigma

We could not agree more with Ide et al. to the suggestion made in their letter that the diagnosis of sclerosing odontogenic carcinoma (SOC) is an exercise in exclusion. Hopefully our case report too amply brings out the fact that this lesion has a histopathology not unique to it. It is the degree of sclerosis seen alongside scant features of malignancy that confuses the so-called SOC with benign odontogenic lesions in small biopsies. Thus to label a lesion as SOC, the whole specimen should be available for demonstrating perineural or intravascular infiltration of odontogenic epithelial cells. The gold standard of diagnosing such lesions seems to lie in the uniform hypercellularity and collagenous sclerosing stroma. Excluding primary intraosseous odontogenic carcinoma is of utmost importance before reporting a case of SOC. Histological evidence of squamous cell carcinoma, either keratinizing or non-keratinizing is one of the diagnostic criteria for PIOC which is not seen in SOC where the cells show uniform cuboidal appearance. Metastatic carcinomas of the jaws being a common occurrence, should be ruled out by a whole body scan. IHC stains do reinforce the origin from odontogenic remnants in the jaws but positivity to low molecular weight cytokeratins to most of these intraosseous jaw malignancies does not provide any specificity. Having said this, it was our experience, that the clinical behavior of the lesion reported here did not follow the known natural progression of intraosseous odontogenic malignancies. A prolonged history of several months suggested an extremely indolent lesion, which was reluctant to metastasize. Thus, if it is a variant of PIOC as the authors of the letter claim, it may need to be included as a separate sub-category. However, as we have stated in our paper, more cases need to be reported before we can attempt to define this lesion's character and subsequently its nosology. Sclerosing odontogenic carcinoma: a morphologic pattern or pathologic entity?Oral Surgery, Oral Medicine, Oral Pathology and Oral RadiologyVol. 115Issue 6PreviewWe enjoyed reading the recent case report of sclerosing odontogenic carcinoma (SOC) by Saxena et al.1 because it aroused our interest again in what has become a controversy in odontogenic tumor pathology, that is, whether SOC exists, and if it does exist, how it should be defined. As hopefully was evident from our previous letter,2 it seems to us illogical to draw any final conclusion that the tumors described by Jones et al.3 and Bennett et al.4 are earlier examples of SOC. The crux of our letter was to select and analyze different types of odontogenic tumors, including our own case, compatible with SOC for discussion. Full-Text PDF