Wide-spectrum Keratin Research Articles

Spindle Cell Atypical Fibroxanthoma: Myofibroblastic Differentiation Represents a Diagnostic Pitfall in This Variant of AFX.

Atypical fibroxanthoma (AFX) is a low-grade, dermal, mesenchymal neoplasm, which lacks a specific lineage of differentiation. The classical histologic appearance of AFX is that of a pleomorphic and spindle cell neoplasm with marked nuclear pleomorphism, mitotic figures, and often prominent storiform pattern that superficially resembles a pleomorphic high-grade sarcoma ("malignant fibrous histiocytoma"). Many histologic variants have been described. We have reviewed 15 cases of AFX characterized by a pure spindle cell morphology that could be easily mistaken for other spindle cell dermal neoplasms. All of our cases were stained with CD68, CD163, CD10, S-100p, p63, wide-spectrum keratin, CD31, CD34, smooth muscle actin (SMA), desmin, calponin, and h-caldesmon. All 15 cases showed an immunoprofile consistent with AFX. In 9 cases, SMA was also strongly expressed; this finding, coupled with the malignant spindle cell histomorphology, can lead to an erroneous diagnosis of cutaneous leiomyosarcoma with potential clinical consequences. Awareness of this pattern of immunoreactivity in this unusual variant of AFX is of importance for avoiding diagnostic misinterpretation. This study intends to characterize the nature and frequency of SMA immunoreactivity in AFX and to discuss the potential diagnostic pitfalls of immunohistochemical markers in distinguishing this entity from other malignant spindle cell neoplasms.

Role of CD10, Wide-Spectrum Keratin, p63, and Podoplanin in the Distinction of Epithelioid and Spindle Cell Tumors of the Skin

Cutaneous epithelioid and spindle cell neoplasms occasionally pose a significant diagnostic challenge on purely histologic grounds. Given the substantial clinicopathologic overlap between these lesions, especially in small biopsies, the use of immunohistochemical studies are essential. We evaluated the utility of a battery of immunohistochemical markers, including podoplanin (D2-40), CD10, p63, and wide-spectrum cytokeratin, for distinguishing cutaneous epithelioid and spindle cell tumors. A total of 81 cases, including 42 atypical fibroxanthoma (AFX), 13 spindle cell melanoma, 10 sarcomatoid carcinoma, 9 leiomyosarcoma (LMS), and 7 leiomyoma, formed the basis of our study. Immunohistochemical results were as follows-AFX: CD10 (35 of 42), p63 (1 of 42), CK (1 of 42), and podoplanin (19 of 42); spindle cell melanoma: CD10 (7 of 13), p63 (0 of 13), CK (0 of 13), and podoplanin (2 of 13); sarcomatoid carcinoma: CD10 (5 of 10), p63 (7 of 10), CK (4 of 10), and podoplanin (7 of 10); LMS: CD10 (4 of 9), p63 (0 of 9), CK (2 of 9), and podoplanin (1 of 9); and leiomyoma: CD10 (0 of 7), p63 (0 of 7), CK (0 of 7), and podoplanin (1 of 7). Our findings showed that the combination of certain immunohistochemical markers may be a useful adjunct in the evaluation of epithelioid and spindle cell tumors of the skin. In this study, we found that a combination of wide-spectrum cytokeratin and p63 are most helpful in the distinction of sarcomatoid carcinomas from other tumors; however, there remains a substantial minority of cases of sarcomatoid carcinoma that will consistently demonstrate negative staining for these markers. We also found that CD10 and podoplanin (D2-40) have limited diagnostic utility in epithelioid and spindle cell tumors of the skin; however, a strong and diffuse pattern of staining will favor the diagnosis of AFX. Caution should also be observed in the diagnosis of spindle cell malignant melanoma because some cases may express CD10, p63, and podoplanin while being nonreactive to S100 protein. Awareness of the limitations of the use of these stains and familiarity with their staining patterns in spindle and epithelioid cell tumors of the skin are extremely important because the prognostic and therapeutic implications for such neoplasms may be quite different.

Immunohistological changes in skin wounds during the early periods of healing in a rat model

The complexity of the wound healing process, which is still poorly understood, prompted us to perform an immunohistochemical investigation using rat skin as an in vivo model. Fifteen Sprague-Dawley rats were included in the experiment. Two round full thickness wounds, 4 mm in diameter, were made on the backs of all rats. Haematoxylin and eosin basic staining as well as antibodies against wide spectrum keratin, keratin 10, keratin 14, α-smooth muscle actin, vimentin, fibronectin, collagens Type 1 and 3, and the transcription factor Sox-2 were applied to paraffin and frozen sections of skin wound specimens two, six and fourteen days after surgery, respectively. New hair follicles with Sox-2-positive cells were present after fourteen days; keratin/vimentin positivity was restricted to specimens of day two. Collagen-3 expression prevailed over collagen-1 expression at all evaluated time intervals, except in the uninjured part of the dermis. In conclusion, rat skin wound healing is a dynamic process which can serve as a model for studying phenomena such as cell-cell interactions and transitions in vivo.

Adenohibernoma of the breast

Dear Sir, Brown fat is mainly found in infants and children and gradually disappears from most sites of the body with increasing age. During adulthood, deposits of brown fat persist around kidneys, adrenal glands, and aorta and within the mediastinum and neck. Tumors composed of brown fat (hibernomas) are rare in breast [1, 2, 4, 5]. A rare case of hamartoma containing brown fat has been reported by Garijo et al. [5]. Adenohibernoma, hibernoma-containing glands, is also a very rare lesion as one case only has been described until now [2]. Here, we are reporting a second case. The patient, a 57-year-old lady, underwent excisional biopsy 2 cm across due to right breast lesion detected mammographically. The family history was unremarkable. Histologically, in addition to tubular carcinoma, an incidental lesion was detected nearby which had not been detected on mammograms. This latter lesion was well circumscribed and measuring 3 mm. It was formed partly by a fibroepithelial proliferation reminiscent of fibroadenoma with myxoid stroma (Fig. 1). Nuclear atypia and epithelial proliferation were not present. The remaining part of the nodular lesion showed dilated glands immersed within fat tissue, which showed uniform, normochromatic, and centrally located nuclei with vacuolated granular eosinophilic cytoplasms consistent with brown fat (Fig. 2). Accordingly, the vacuolated granular brown fat cells were positive with avidin–biotin complex peroxidase for S-100 protein (Dako, polyclonal, 1:1500; Fig. 3) and negative for wide spectrum keratin (Dako, MNF116, 1:200) and cluster of differentiation (CD)68 (Neomarkers, monoclonal, MAC387, 1:200). There was no residual lesion within the re-excision specimen which consisted of fibrofatty tissue measuring 4 cm. Seven lymph nodes from lower axillary level were reactive. There is no evidence of disease after a 6-year follow-up. Adenolipomas are lesions composed of glands immersed in adult classical adipous tissue and are closely associated with hamartomas. Both lesions are fibroglandular and are well circumscribed [3] and the amount of fat is by definition conspicuous in adenolipomas compared with hamartomas. Hamartomas are lesions that result from faulty development in an organ, composed of an abnormal mixture of normally occurring tissue elements or an abnormal proportion of a single element normally present at that site. Brown fat is not a normal constituent of adult breast tissue and in this respect adenohibernomas cannot be regarded as hamartomas. Damiani and Panarelli [2] suggested a hamartomatous origin from remnants of fetal brown adipose tissue or, alternatively, the possibility of de novo mixed proliferation showing brown fat differentiation in its mesenchymal component for adenohibernomas. In addition, the focus that the granular cells are associated to a fibroadenoma is a further proof that the adenohibernoma is not a hamartoma. This situation was favored by Fisher et al. [3] who believed that fibroadenomas and hamartomas were Virchows Arch (2008) 452:351–352 DOI 10.1007/s00428-007-0553-x

Malignant mixed epithelial and stromal tumor of the kidney with rhabdoid features: report of a case including immunohistochemical, molecular genetic studies and comparison to morphologically similar renal tumors

Mixed epithelial stromal tumor of the kidney (MEST)/adult cystic nephroma (CN) is a lesion characterized by epithelial lined tubular or cystic structures interspersed within a variably prominent, distinctive spindle-cell stroma. Although typically benign, cases with malignant features have been reported. Herein, we report a MEST/CN with malignant stromal features and rhabdoid differentiation arising in the left kidney of an 84-year-old woman. Histologically, the tumor displayed multiple tubules and variably sized cystic structures lined by benign epithelium with an intervening malignant-appearing spindle-cell stroma. The malignant stroma displayed condensation in the regions surrounding the epithelial component consistent with the ovarian-like stroma typically observed in MEST/CN. In addition, the stromal cells displayed extensive rhabdoid differentiation. Immunohistochemical analysis revealed strong expression of cytokeratin 7, CAM 5.2, AE1/AE3, wide-spectrum keratin, and epithelial membrane antigen by the epithelial component. The stromal component displayed strong immunohistochemical expression of WT-1, CD-99, CD-56, INI1, and estrogen receptor; focal actin positivity; and was negative for desmin, myogenin, and progesterone receptor. Analysis by reverse transcriptase polymerase chain reaction failed to identify the SYT-SSX1 or SYT-SSX2 fusion transcripts characteristic of synovial sarcoma. To our knowledge, this represents the first report in the literature of malignant MEST with rhabdoid features and suggests that this entity should be considered in the diagnosis of renal stromal malignancies with prominent rhabdoid features.

Spindle and giant cell type undifferentiated carcinoma arising in the common bile duct: A case report

We report on a 61-year-old Japanese male with a pedunculated tumor in the common bile duct. The tumor consisted of two types of neoplastic cells. The majority showed atypical spindle- and giant-shaped features and proliferated densely in an inflammatory stroma, revealing a sarcomatous pattern. They expressed vimentin, KL-1, and CAM5.2. The remaining minority showed glandular and tubular features, occupied only less than 5%, located only in the tumor surface, and expressed wide spectrum keratin, KL-1, CAM5.2, epithelial membrane antigen, AE1/AE3, and carcinoembryonic antigen. CD68-positive osteoclast-like giant cells were also observed. Therefore, the patient was diagnosed as having an undifferentiated carcinoma, spindle and giant cell type.

Spindle cell carcinoma arising in the pharynx, with granulocytosis and high serum granulocyte colony stimulating factor titre

We report the case of a 67-year-old man with a left pharyngeal tumour, whose peripheral blood showed granulocytosis (white blood cell count, 58,300/microl) and a high serum granulocyte colony stimulating factor titre (184 pg/ml). The tumour showed pleomorphic proliferation of atypical spindle cells in a myxomatous stroma, revealing a sarcomatous pattern. The spindle-shaped neoplastic cells had irregularly shaped nuclei, a thick nuclear membrane, prominent eosinophilic nucleoli and abundant cytoplasm. They strongly expressed wide-spectrum keratin, cytokeratins (CAM5.2, MNF116), vimentin and vascular endothelial growth factor. A few neoplastic cells expressed granulocyte colony stimulating factor. A spindle cell carcinoma was diagnosed. This may be the first documented case of a granulocyte colony stimulating factor producing cancer arising in the pharynx. The patient died four months after the initial symptoms appeared.

Primary germ cell tumors of the mediastinum: II. Mediastinal seminomas--a clinicopathologic and immunohistochemical study of 120 cases.

Primary seminomas of the mediastinum are unusual neoplasms that are morphologically indistinguishable from their gonadal counterparts but may have different biologic behavior because they arise at this particular location. The clinical and pathologic features in 120 cases of primary mediastinal seminoma were reviewed, and the immunohistochemical staining patterns in 50 of these tumors were also analyzed. The patients were all men between the ages of 14 and 79 years (mean age, 46.5 years). Their clinical symptoms included cough, chest pain, and dyspnea. In some patients, the lesions were asymptomatic and discovered incidentally on routine chest radiographs. None of the patients had a previous history of testicular neoplasm or tumor elsewhere. Macroscopically, the tumors were described as soft and tan, with a slightly lobulated cut surface, and measured up to 16 cm in greatest dimension. Histologically, the morphologic features were similar to those of tumors occurring in the gonads, namely, a neoplastic proliferation of round-to-polygonal cells with indistinct cell borders, clear-to-lightly-eosinophilic cytoplasm with round-to-oval nuclei and prominent nucleoli, associated with a prominent inflammatory background composed mainly of mature lymphocytes. Necrosis, hemorrhage, multinucleated giant cells, granulomatous reaction, and remnants of thymic tissue were observed in a variable number of cases; mitoses were rare. Immunohistochemical studies in 50 cases showed cytoplasmic staining with placental alkaline phosphatase in 80% of the tumors, focal dotlike positivity for CAM 5.2 low-molecular-weight keratins in 75%, focal cytoplasmic staining for wide-spectrum keratin in 70%, focal positive reaction with vimentin in 70%, and focal positivity with HCG in singly scattered cells in 5%. Immunostains for carcinoembryonic antigen, epithelial membrane antigen, and alpha-fetoprotein were negative in all the cases studied. Fifty patients were Stage I, 3 patients were Stage II, and 12 patients were Stage III. Clinical follow-up information was obtained for 65 cases (54%). Forty-nine patients were alive and disease free after a period ranging from 1 to 19 years (mean follow-up, 10 years). Sixteen patients died within the same period and were found to have metastases to distant organs. Of the 16 patients who died, 6 showed extension of the tumor outside of the mediastinal compartment at the time of initial diagnosis (Stage III lesions). Aside from clinical staging, the authors' findings also suggest that patients >37 years have worse outcomes than younger individuals. The authors were unable to find any correlation between histopathologic features and clinical behavior in any of these cases. Clinical and pathologic staging of mediastinal seminomas are important parameters that can be useful in determining the clinical outcomes of patients with these tumors. Tumor invasion into adjacent organs represents a marker of increased morbidity and mortality. The authors' findings suggest that patients with mediastinal seminomas may have a very good prognosis when the diagnosis is made early; patients with more advanced lesions may require more aggressive therapy for improved local control and prevention of distant metastases.

Metastatic adenocarcinoma to the brain: An immunohistochemical approach

The diagnosis of metastatic adenocarcinoma to the brain of unknown primary is problematic, and the role of immunohistochemistry in identifying a source has not been fully characterized. Sixty-eight metastatic adenocarcinomas of the brain with known primaries were immunostained with antibodies to cytokeratin 7 (CK7), cytokeratin 20 (CK20), CAM 5.2, wide-spectrum keratin (WSK), gross cystic disease fluid protein-15 (GCDFP-15), glial fibrillary acidic protein (GFAP), estrogen receptor (ER), and progesterone receptor (PR). True positive staining was defined as CK7 in lung or breast; CK20 in gastrointestinal; and GCDFP-15, ER, and PR in breast carcinomas. CK7 immunoreactivity was present in all 27 lung carcinomas and 14 of 15 breast carcinomas with a sensitivity of 98% and specificity of 78%. CK20 stained 15 of 16 GI carcinomas with a sensitivity and specificity of 94%. None of the cytokeratins stained surrounding brain tissue. GCDFP-15, ER, and PR had sensitivities of 33% 33%, and 87%, with specificities of 92%, 84%, and 28%, respectively. PR often stained nuclei of normal brain tissue and was accentuated in areas of necrosis or cautery artifact. CK7 and CK20 are highly sensitive and specific in patients with metastatic adenocarcinoma to the brain of unknown primary. GCDFP-15 and ER are relatively specific, but insensitive markers, and PR is nonspecific and difficult to interpret.

HBcAg and HBsAg expression in ductular cells in chronic hepatitis B.

The possible involvement of bile duct epithelium (BDE) in chronic hepatitis B was examined by immunohistochemical investigation of HBcAg and HBsAg expression in biliary cells in 47 liver biopsies with both viral antigens detectable in hepatocytes. HBcAg- and HBsAg-positive cells were identified in nine and five cases, respectively, in atypical and occasionally in typical ductules in cases of acute exacerbation, chronic active hepatitis and active cirrhosis. Atypical ductules were usually located in areas of periportal fibrosis and in cirrhotic septa. Liver cell plates expressing viral markers and undergoing ductular transformation (positive reaction of hepatocytes to BDE-specific, wide-spectrum keratin) were also observed in acinar zone 1, at the periphery and within parenchymal nodules in a number of cases. The presence of both viral antigens in atypical ductules in cases of advanced chronic liver disease most probably expresses the persistence of the virus in cells deriving from biliary metaplasia of infected hepatocytes. However, the detection of the virus in a few typical ductules is indicative of a direct viral infection. According to these findings, ductular cells seem to serve as a suitable host for HBV, their genotype permitting viral replication and antigen production.

IMMUNOHISTOCHEMISTRY OF ECCRINE POROCARCINOMA

The eccrine porocarcinoma is a rare adnexal tumor of human skin. It has been related to the acrosyringeum of the sweat gland. An immunohistochemical study on paraffin sections of eight porocarcinomas and a control group of 29 poromas was conducted to investigate the differentiation of porocarcinomas. Antibodies against (neuro-) glandular antigens and selected intermediate filaments were used for indirect immunoperoxidase staining with amino ethyl carbazole. Porocarcinomas disclosed variable amounts of cells labeled with CEA, S100A, LS59, NKI/C-3, Cam 5.2, Vim9(1), and wide spectrum keratin. Cellular phenotypes showed greater variability than the benign poromas. The immunostaining patterns of porocarcinomas suggest a differentiation program towards inner duct cells and myoepithelium thereby questioning their classification as acrosyringeal neoplasms.

Simultaneous carcinoma involving the endometrium and the ovary. A clinicopathologic, immunohistochemical, and DNA flow cytometric study of 18 cases

Eighteen carcinomas involving both the endometrium and the ovary were studied. Stage, size, bilaterality and pattern of ovarian involvement, histologic types and grades, presence of endometrial hyperplasia or ovarian endometriosis, myometrial, tubal, lymphatic and blood vessel invasion, and follow-up of the patients were all evaluated. Accordingly, the cases were classified as follows: Group A (nine cases), two separate primary tumors; and Group B (nine cases), uterine primaries with ovarian metastasis or ovarian primaries with uterine metastasis. Immunohistochemical stains (CAM 5.2, wide-spectrum keratin, vimentin, carcinoembryonic antigen (CEA), CA 12.5, CA 19.9) were performed in all cases. Flow cytometric determination of nuclear DNA was done in 13 (seven Group A and six Group B tumors). Of the nine cases with independent primary tumors, seven showed different immunohistochemical profiles in the ovarian and uterine tumors, whereas only four of the nine metastatic ones had similar staining characteristics. Five cases with independent primary tumors, but only one of the metastatic group, exhibited different aneuploid stemlines in the endometrial and ovarian tumors. The other seven (two independent and five metastatic) cases had similar DNA indexes in both tumors. Immunohistochemical and DNA flow cytometric study may be of some value for the distinction between metastatic and independent tumors, but differential diagnosis must presently rely largely upon conventional clinicopathologic criteria.

Rhabdoid tumors of soft tissues: A clinicopathologic study of 26 cases enrolled on the intergroup rhabdomyosarcoma study

Twenty-six cases of malignant soft tissue tumors with features similar to renal rhabdoid tumors were identified among approximately 3,000 childhood sarcomas entered on Intergroup Rhabdomyosarcoma Studies I-III. The tumors consisted of polygonal cells with vesicular nuclei and prominent nucleoli and cytoplasmic intermediate filament inclusions as identified by electron microscopy and immunohistochemistry. The growth pattern was predominantly solid or solid-trabecular. Immunohistochemistry showed vimentin, wide spectrum keratin, and epithelial membrane antigen to be the most consistent antigenic phenotypes. Eleven patients were infants less than 1 year of age. The tumors affected predominantly soft tissues of proximal extremities, trunk, and retroperitoneum/pelvis/ abdomen. Nineteen patients died within 1 to 82 months (median, 6 months) from the start of treatment. Five patients have survived the disease for 2 to 13 years. When compared with the survival analysis of 991 Intergroup Rhabdomyosarcoma Study II patients, it was obvious that this group of tumors fares very poorly ( P < .001). The tumor belongs to the group of soft tissue neoplasms showing mesenchymal and subtle epithelial differentiation, similar to epithelioid sarcoma. Because of its identifiable histology, site and age distribution, and poor outcome, it warrants a status as an independent entity.

Reactivity of Antibody to Wide-Spectrum Keratin

Reactivity of Antibody to Wide-Spectrum Keratin Get access John K. C. Chan, M.B., B.S., John K. C. Chan, M.B., B.S. Institute of Pathology Queen Elizabeth Hospital Wylie Road Kowloon, Hong Kong Search for other works by this author on: Oxford Academic Google Scholar Stephen W. Leung, A.I.M.L.S. Stephen W. Leung, A.I.M.L.S. Institute of Pathology Queen Elizabeth Hospital Wylie Road Kowloon, Hong Kong Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 88, Issue 4, 1 October 1987, Page 535, https://doi.org/10.1093/ajcp/88.4.535 Published: 01 October 1987