[Invasive lobular carcinoma of basal-like subtype of breast: a clinicopathologic analysis].

OBJECTIVE: To investigate the clinicopathologic features, clinical progress and prognosis of the basal-like subtype of invasive lobular carcinoma (ILC) of the breast. METHODS: Four cases of ILC were analyzed by detailed histopathologic observation and immunohistochemical staining for E-cadherin, p120 catenin, ER, PR, HER2, CK5/6, EGFR, p63, p53, Ki-67 using MaxVision method. The follow-up and clinical data were analyzed. RESULTS: Morphologically, one case was mixed ILC and three cases were pleomorphic ILC. The tumor cells were negative for E-cadherin except one case with focal membrane positivity, and all showed p120 catenin cytoplasmic positivity except one case with focal membrane positivity. All cases were negative for ER, PR and HER2 (triple negative), and positive for EGFR and CK5/6. Two cases were positive for p63. The cases were partly and weakly positive for p53, and the Ki-67 positive rate was between 30% and 75%. Follow-up data showed that two cases developed chest wall metastases, and in one case, there was progression to liver and abdominal metastases. CONCLUSIONS: ILC of the breast are ER, PR and HER2 "triple negative", CK5/6 and EGFR positive, indicative of basal-like characteristics. Basal-like subtype of ILC are peculiarly prone to metastasis and poor response to chemotherapy, suggesting that it is associated with poor prognosis.

[Morphologic evaluation of papillary carcinoma of the breast featuring expansile invasion].

OBJECTIVE: To study the pathology, diagnosis and differential diagnosis of papillary carcinoma of the breast featuring expansile invasion. METHODS: Morphologic analysis and immunohistochemical study using MaxVision method were carried out in 25 cases of papillary carcinoma of the breast featuring expansile type of invasion. RESULTS: All the 25 cases were female, and ranged from 26 to 84 years old in age with median of 69. The diameters of the neoplasms were from 1 cm to 5 cm, among which those of two cases were 4 cm and 5 cm respectively and the others were less than 2.5 cm. The tumor appeared solid and well-demarcated on gross examination. Histologically, the tumor was non-encapsulated. In some cases, the tumor tissue was separated by fibrous septa or intervening native breast tissue. The tumor was composed of arborizing papillae with fibrovascular cores, associated glandular fusion and cribriform pattern. The fibrovascular cores were covered by cuboidal to columnar cells. In 3 of the cases studied, focal transition with micropapillary ductal carcinoma-in-situ was demonstrated. The tumor cells showed mild or moderate degree of nuclear pleomorphism and contained amphophilic to eosinophilic cytoplasm. Mitotic figures were not frequently seen. One case displayed squamous metaplasia and 4 cases showed apocrine metaplasia. Dimorphic features were identified in 2 cases. The stromal tissue within the tumor was often scanty and sometimes sclerotic, associated with various degrees of inflammatory infiltrate and hemosiderin deposition. Immunohistochemical study for smooth muscle actin, p63, CD10 and CK5/6 showed negative staining in all of the 25 cases studied, including the 2 cases with dimorphic features. Seven cases had breast cancer marker study performed. Six cases were positive for estrogen receptor and progesterone receptor. HER2 oncoprotein was not over-expressed in 6 cases. Nine patients underwent axillary dissection and 2 of them showed axillary nodal metastasis. CONCLUSIONS: Diagnosis of papillary carcinoma of the breast is one of the most difficult areas in breast pathology. Demonstration of expansile type of invasion, when coupled with complex papillary fusion, cribriform pattern and absence of myoepithelial cells on immunohistochemistry, is helpful in arriving at a correct diagnosis.

Is mammary not otherwise specified-type sarcoma with CD10 expression a distinct entity? A rare case report with immunohistochemical and ultrastructural study.

Mammary sarcoma is extremely rare and the diagnosis is established only after metaplastic carcinomas and malignant phyllodes tumours are excluded. A rare case of not otherwise specified-type sarcoma with CD10 expression in the left breast in a 45-year-old female was presented. It was a high-grade tumour composed of spindle cells histologically. The immunohistochemical results showed that CD10, vimentin and EGFR were positive diffusely and SMA presented focally, whereas epithelial markers and other myoepithelial or myogenic markers were all negative. The electron microscope investigation demonstrated fibroblast-like features. The exact entity of the tumour remains to be studied because it resembles undifferentiated sarcoma or sarcomatoid metaplastic carcinoma to some degree, as well as high-grade malignant phyllodes tumour in particular. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9019879588725702.

[Granulomatous lobular mastitis associated with mammary duct ectasia: a clinicopathologic study of 32 cases with review of literature].

OBJECTIVE: To study the clinicopathologic features of granulomatous lobular mastitis and mammary duct ectasia. METHODS: The clinicopathologic data from August 2005 to May 2013 of 32 cases of granulomatous lobular mastitis and mammary duct ectasia were retrospectively reviewed. RESULTS: The age of patients ranged from 26 to 45 years. Two patients had no history of delivery. Fourteen patients had no history of lactation or lactational disorder in the lesional side. Most of the remaining patients had history of breast feeding. Gross examination showed that the lesions were poorly circumscribed and varied from 3 to 12 cm in greatest dimension. Tiny abscess cavities, ranging from 0.1 to 0.5 cm in diameter and containing light yellowish to greyish secretion, were demonstrated. Histologic examination showed granuloma formation and ductal dilatation. Eleven patients had received antibiotic treatment. Twelve cases were complicated by sinus formation related to skin incision and drainage. The duration of follow-up ranged from 5 to 90 months. Three cases showed ipsilateral recurrence and 3 cases had similar pathology in the contralateral breast. Four patients defaulted follow-up. CONCLUSIONS: Granulomatous lobular mastitis is associated with mammary duct ectasia. Accurate pathologic diagnosis is prudent for clinical management and control of local recurrence.

[Clinicopathologic features of collagenous spherulosis of the breast].

OBJECTIVE: To investigate the morphological features, immunohistochemical phenotype, diagnosis and differential diagnosis of collagenous spherulosis of the breast. METHODS: Clinicopathologic observation, immunohistochemistry using EnVision method and histochemical staining were applied in 33 cases of collagenous spherulosis of the breast. RESULTS: Collagenous spherulosis of the breast was a benign lesion, consisting of proliferative myoepithelial and ductal epithelial cells. These cells were arranged in a cribriform pattern with esinophilic, round, oval or star-shaped fibrillary spherules in the lumen.SMA, calponin and p63 by immunohistochemistry identified the proliferative myoepithelium, while E-cadherin identified the proliferative ductal epithelial cells. The esinophilic spherules were stained with collagen type IV, AB-PAS and reticulin. Collagenous spherulosis was often found in sclerosing adenosis. CONCLUSIONS: Collagenous spherulosis of the breast is often associated with other diseases. It has special morphological presentation and is easily confused with malignant tumors such as adenoid cystic carcinoma or cribriform carcinoma in situ, and needs to be differentiated from these disease entities.

[Clinicopathologic features of micropapillary variant of pure mucinous carcinoma of breast].

OBJECTIVE: To study the clinicopathologic features of pure mucinous carcinomas of the breast with diffuse micropapillary pattern. METHODS: Twenty-six cases of micropapillary variant of pure mucinous carcinoma of the breast were retrospectively reviewed by light microscopy, immunohistochemistry and clinical data analyses. RESULTS: The age of 26 female patients ranged from 30 to 77 years old, of which 12 cases with clinical details available were mean 54 years old. The tumor diameter ranged from 0.8 to 9.0 cm (mean 3.2 cm). Ipsilateral axillary nodal metastases were identified in 3 cases. Cutaneous involvement was also found in 2 cases. The tumor cells showed the similar architectural arrangement as in invasive micropapillary carcinoma, with peripheral borders of the cell clusters highlighted by epithelial membrane antigen. Various amount of mucin occupied the retraction spaces around the tumor cells. Compared with conventional pure mucinous carcinoma of the breast, mucinous carcinomas with micropapillary pattern showed different nuclear grades (19 cases of grade I, 2 cases of grade II, 5 cases of grade III). The micropapillary cell clusters varied in size (22 cases of big micropapillary and 4 cases of small). Intraductal carcinoma was observed in 12 cases. Calcification and psammoma bodies were observed in 8 cases. Immunophenotyping, the tumor cells were with higher expression of hormone receptors, but HER2 were negative. Ki-67 positive index was 1% ∼ 70%. Neuroendocrine differentiation was observed in 6 cases. CONCLUSIONS: The micropapillary variant of pure mucinous carcinoma of the breast, which mainly occurs in younger women, may carry the similar propensity for angioinvasion and nodal metastasis as infiltrating micropapillary carcinoma at least in cases with high nuclear grade. This morphologic subtype needs to be distinguished from conventional pure mucinous carcinoma of the breast and treated properly.

[Pathologic diagnosis and differential diagnosis of low-grade adenosquamous carcinoma of breast and syringomatous adenoma of nipple].

OBJECTIVE: To investigate the pathologic and immunohistochemical features, diagnosis and differential diagnosis of low-grade adenosquamous carcinoma of the breast and syringomatous adenoma of the nipple. METHODS: Six cases of low-grade adenosquamous carcinoma of the breast and four cases of syringomatous adenoma of the nipple were examined histologically and immunohistochemically (MaxVision method), and the literature was reviewed. RESULTS: The two types of tumors were similar in morphology, but located in different regions with low-grade adenosquamous carcinoma being present in the deep parenchyma and syringomatous adenoma in nipple. Both types of tumors were composed mainly of well-differentiated glands with angulated, comma shaped or polliwog appearance in a disordered infiltrative pattern. The tumor cells also formed solid tubules, strips or nests, with frequent areas of squamoid differentiation. Mitosis was rare. The interstitial tissue showed abundant spindle cells or sclerotic fibrosis with mixed inflammatory cells infiltration. One case of low-grade adenosquamous carcinoma showed a concomitant malignant adenomyoepithelioma, and another case showed concomitant spindle cell metaplastic carcinoma. One case of syringomatous adenoma involved the deep parenchyma. Immunohistochemistry of low-grade adenosquamous carcinoma showed that CK5/6 and p63 were positive in the outer layer of the glands and the squamoid epithelium, and CD10 was also positive in the outer layer of the glands. ER and HER2 were negative, and PR was also negative except for one case in which the spindle cells were positive for CK5/6, AE1/AE3 and PR focally. Immunostaining of syringomatous adenoma demonstrated that p63 and CK5/6 were positive in the outer layer of the glands and the squamoid epithelium. Calponin, SMA, ER, PR and HER2 were all negative. CONCLUSIONS: Low-grade adenosquamous carcinoma of the breast and syringomatous adenoma of the nipple are similar in morphology and immunohistochemical phenotype, while the biological features are opposite due to different locations. The differential diagnoses include tubular carcinoma, adenosquamous carcinoma, radial sclerosing lesions and others.

[Neuroendocrine carcinoma of breast: a study of tumor morphology and subtyping].

OBJECTIVE: To study the clinical features and histopathology of the neuroendocrine carcinoma (NEC) of the breast. METHODS: Twenty-two cases of NEC of the breast were analysed by morphology and immunohistochemistry using synaptophysin, chromogranin A, NSE, CD56, estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, CK5/6, CK14, p63, E-cadherin, p120, p53 and Ki-67 staining. HER2 gene amplification was detected by fluorescence in situ hybridization (FISH) for cases with HER2 protein expression 2+. The diagnosis of breast NEC relies on the expression of neuroendocrine markers expression in more than 50% of tumor cells, and no evidence of neuroendocrine carcinoma in any other parts of the body at the same time. RESULTS: The patients aged from 31 to 96 years (mean 65.2 years), and all were female but one. Amongst the 22 patients studied, the NECs were in the left breast in 15 cases (68.2%) and in the right breast in seven cases (31.8%); the tumor size was 0.5 to 5.5 cm (mean 2.7 cm). Lymph node metastasis was found in six cases. Basing on the morphologic features, these 22 cases were categorized into six subtypes including nine cases of solid cohesive, six of mucinous, three of solid papillary, two of small cell, one of large cell and one of alveolar variants. Immunohistochemically, the expression rate of markers was 100% (22/22) for synaptophysin, 12/13 for NSE, 54.5% (12/22) for chromogranin A, and 5/16 for CD56. Also, 90.5% (19 of 21) of cases expressed ER, 81.0% (17 of 21) of cases expressed PR, and none expressed EGFR, CK5/6, CK14 and p63. HER2 protein over-expression (3+) and gene amplification was not detected in any case. All cases (19/19) were positive for membrane staining for E-cadherin and p120. p53 expression was seen in 6 of 17 cases. Ki-67 labeling index was less than 3% in 9.5% (2/21) of the cases, 3% to 20% in 66.7% (14/21) of the cases and more than 20% in 23.8% (5/21) of the cases. Both cases of HER2 (2+) did not show gene amplification by FISH. On the basis of immunophenotypes, most of the breast NECs were of the luminal molecular subtype, but not HER2-overexpression or basal-like subtypes. CONCLUSIONS: NEC of breast more likely occurs in elderly patients and in the left breast than the right breast. The most common morphology is the solid cohesive subtype, followed by the mucinous variant.

[Expression of E-cadherin, p120catenin and 34ßE12 in invasive lobular carcinoma of breast and their roles in diagnosis].

OBJECTIVE: To investigate expressions of E-cadherin (E-cad), p120catenin (p120), 34ßE12 in invasive lobular carcinomas of the breast and their roles of diagnoses. METHODS: The 81 cases of ILC, including 67 cases of pure type and 14 cases of ductal-lobular mixed type, which had been diagnosed in our department were collected and immunohistochemistry of E-cad, p120 and 34ßE12 were performed. All the cases were diagnosed again according to morphology and immunophenotypes (MaxVision method), and difference of diagnoses and expressions of the three indexes were analysed. RESULTS: Sixty four of 81 cases were permantly diagnosed of ILC. In the 61 cases of pure type, 54 cases displayed E-cad negative and p120 cytoplastic positive, 1 case displayed E-cad negative and p120 atypical positive, 3 cases displayed E-cad membrane positive and p120 cytoplastic positive, and 3 cases displayed both atypical positive. Fifty two of 61 cases displayed 34ßE12 positive. The 3 cases of mixed type displayed p120 cytoplastic positive, and 2 cases displayed E-cad negative and 1 case displayed atypical positive. All the 3 cases displayed 34ßE12 positive. CONCLUSIONS: The diagnosis of ILC is one of the most difficult problems in breast pathology, and combination of E-cad and p120 immunostaining is an effective method for assistance. It needs further studies for invasive ductal carcinomas with morphological features of lobular carcinomas.

[Granulomatous lobular mastitis: a clinicopathologic study of 68 cases].

OBJECTIVE: To study the clinical and pathologic features of granulomatous lobular mastitis (GLM). METHODS: Sixty-eight cases of GLM were retrieved from the archival file. The clinical data and histologic features were retrospectively reviewed. RESULTS: Sixty-eight patients presented with breast mass. Ulceration in overlying breast skin was seen in 9 cases. Most of the patients had history of breast feeding. None of them had evidence of specific infections involving the breast. The clinical and radiologic features mimicked malignancy. Histologically, GLM was characterized by the presence of non-necrotizing granulomas, usually admixed with neutrophils and associated with benign ductolobular units. The ductolobular architecture was still preserved. The duration of follow up ranged from 6 to 36 months. Four patients suffered from disease recurrence. CONCLUSIONS: GLM shows clinical and radiologic features reminiscent of breast cancer. Correct diagnosis requires histologic examination of the biopsy specimens.

[Pathological study of radial sclerosing lesions].

OBJECTIVE: To investigate the pathological diagnostic features and the differential diagnosis of radial sclerosing lesions of the breast. METHODS: Morphological observation and immunohistochemistry were applied to forty-four cases of radial sclerosing lesions of the breast. RESULTS: All forty-four patients were females, the mean age was 40.3 years (range 17 to 54 years). In the 31 consultation cases, 13 were misdiagnosed as carcinoma. The lesions had a radiating outline, and a central scar area where squeezed or pressed irregular shaped tubules were frequently seen. Dilated tubules and proliferated ducts or lobules were seen radically arranged at the periphery accompanied sometimes with the apocrine glands or columnar cell metaplasia and hyperplasia. Aside, there were 14 cases displaying necroses and 8 cases showing atypical ductal hyperplasia. Immunostaining showed myoepithelial cells around the pseudo-infiltrating tubules, and the florid proliferating epithelial cells were positive for CK5/6. CONCLUSIONS: Radial sclerosing lesions of the breast possess characteristic histological features, and may be misdiagnosed as carcinoma. The lesions should be differentiated from ductal carcinoma in situ, lobular neoplasia, tubular carcinoma and invasive ductal carcinoma.

[Nipple adenoma: report of 18 cases with review of literatures].

OBJECTIVE: To investigate the clinicopathological and immunohistochemical features, diagnosis and differential diagnosis of nipple adenoma of the breast. METHODS: Morphological observation and immunohistochemistry were applied to 18 cases of nipple adenoma with a review of the related literatures. RESULTS: The neoplasms were localized at nipples or under the areola of breast, adherent to the epidermis, mainly composed of dilated ducts in a tubular appearance associated with fibrotic matrix. The glandular epithelium showed various type of proliferation, forming thick layers or complex structures such as papillae, micropapillae, tufts, fronds, arcades or bridges accompanying with solid or cribriform cell nests. The tumor cells were crowding, lack of an uniform morphology and polarity with intact myoepithelial cells around the ducts. By immunostaining, the glandular epithelium was diffusely positive for 34betaE12, patchily positive for CK5/6, and negative for p53 and c-erbB-2. The myoepithelium, positive for p63, smooth muscle actin and Calponin, was well preserved and outlining the ducts. CONCLUSIONS: Nipple adenoma is an infrequent type of benign breast neoplasm, presenting as sclerosing papilloma, papillomatosis or florid sclerosing adenosis. It is easily confused with atypical ductal hyperplasia/low grade ductal carcinoma in situ, invasive ductal carcinoma or low grade adenosquamous carcinoma. A correct diagnosis is based on the peculiar location and morphology of the tumor, and immunohistochemistry is helpful in some cases.

Localized malignant myxoid anaplastic mesothelioma of the pericardium.

UNLABELLED: Primary malignant mesothelioma of the pericardium is a rare cardiac neoplasm. Most are diffuse and have poor prognosis with median survival of six months. In the paper, we describe a young male patient having no exposure history of asbestos with localized malignant myxoid mesothelioma of the pericardium. The tumor displayed significant myxoid change in stroma, and anaplastic cytology, including pleomorphy, poor cohesion, prominent nuclei, with high mitoses, which led to difficulty in diagnosis. The tumor showed typical immunohistochemical phenotypes of mesothelioma, positive for WT-1, calretinin and CK5/6. Ki-67 labeling index was about 50% in general and nearly 80% in the most active areas. The patient showed better outcome. The report suggests the diagnosis of myxoid mesothelioma is supposed to rely on clinical data, and immunohistochemistry is assumed to be for differentiation. KEYWORDS: Myxoid mesothelioma; Anaplastic; Diagnosis; Immunohistochemistry; Prognosis.

[Morphological features of basal-like subtype invasive carcinoma of breast].

OBJECTIVE: To summarize the morphological features of basal-like subtype of invasive breast carcinoma (BLSIBC), and to look for diagnostic clues for its recognition. METHODS: Immunohistochemistry was performed in 109 cases of invasive ductal carcinoma, with CK5/6, CK14, CK8/ 18, 34betaE12, calponin, p63, CD10, ER, PR and c-erbB-2 monoclonal antibodies. Five subtypes were classified according to immunophenotypes: luminal A subtype (ER+/HER2-), luminal B subtype (ER+/ HER2+), normal breast-like subtype (ER/HER2-), HER2-overexpressing subtype and BLSIBC which was identified with at least one kind of basal-like cytokeratins or markers of myoepithelium and ER/HER2. The microscopic features of basal-like subtype were also analyzed. RESULTS: The number of luminal A case was 48 (44.0%), luminal B 15 (13.8%), HER2 over-expressing 15 (13.6%), normal breast-like 10 (9.1%), basal-like subtype 19 (17.4%). Besides, the other two cases expressed c-erbB-2 or/and ER plus markers for myoepithelium, thus were excluded from all the five mentioned subtypes. Of the 19 basal-like subtype, CK5/6 was expressed in 16 cases, CK8/18 in 17 cases, CK14 in 11 cases, 34betaE12 in 18 cases, p63 in 5 cases, CD10 in 6 cases, and calponin in 1 case. The diameter of the BLSIBC cases was 1.2-7 cm (averagely 3.9 cm) , and in 6 cases, the tumor diameter was >5 cm. Only one case displayed extensive in situ component, 9 cases were grade 2, and 9 cases were grade 3. Compared to non basal subtype, there were significantly more high grade cases (P <0.01). The morphological features of basal-like subtype were summarized as the followings: pushing margin (13 cases), lymphocytic tissue hyperplasia (18 cases), nest or sheet arrangement (18 cases), nucleus grade 3 and scattered giant or bizarre nuclei (17 cases), syncytial growth (7 cases), and comedo-like necrosis (17 cases). The frequency of these features were significantly more common than non basal subtype (P <0.01). CONCLUSION: The morphologic diagnostic features of BLSIBC are pushing margins, lymphocyte infiltration, comedo-like necrosis, gigantic cell and syncytial growth.

[Clinicopathological features of the mucocele-like lesions in the breast].

OBJECTIVE: To study the clinical and pathological features of mucocele-like lesions in the breast. METHODS: Nine cases of mucocele-like lesions in the breast were reported for the morphological and immunohistochemical features, the differential diagnosis, and a literature review. RESULTS: All nine cases were from female patients, aged 23 to 43 years (mean 34 years), clinically presented with palpable breast masses. Grossly, the lesions were multi-cystic with colloidal appearances. Histologically, the lesions consisted of multiple cysts filled with colloid, these cysts were lined with tubular, cuboidal or columnar epithelium. There were superimposed papillary epithelial hyperplasia in three cases and atypical ductal hyperplasia in one. Extravasated mucinous lakes were seen in the stroma, but without cellular component. CONCLUSION: Mucocele-like lesions of the breast is a group of mostly benign disease, and the differential diagnosis should include mucinous carcinoma.

[Spindle cell carcinoma of breast with neuroendocrine differentiation].

OBJECTIVE: To describe the morphologic features and immunohistochemistry of spindle cell carcinoma of breast with neuroendocrine differentiation. METHODS: Retrospective review of 2500 cases of breast carcinoma showed 5 cases (0.2%) with a predominance (> 80%) of spindle cell component. Amongst the 5 cases studied, 2 represented intraductal spindle cell carcinoma and 3 represented invasive spindle cell carcinoma. The paraffin sections were stained with hematoxylin and eosin, alcian blue, periodic acid-Schiff and reticulin stain. Immunohistochemical studies for AE1/AE3, CEA, EMA, CK7, 34betaE12, NSE, synaptophysin, chromogranin A, Leu-7, vimentin, S-100, SMA, calponin, estrogen receptor, progesterone receptor, c-erbB2, E-cadherin, Ki-67 and p53 were also carried out. Follow-up information was available in 4 of the 5 cases. RESULTS: The mean age of the patients was 68 years. Histologically, all tumors were predominantly composed of elongated spindle cells. Three of these cases also contained tumor cells with vacuolated cytoplasm, alcian blue-positive tumor cells were observed in 4 cases. Immunohistochemically, the spindle tumor cells in all cases expressed AE1/AE3, CEA, EMA, E-cadherin and synaptophysin. CK7 was positive in 4 cases, NSE in 3 cases, chromogranin A and Leu-7 in 2 cases. Estrogen receptor was expressed in 4 cases and progesterone receptor in 2 cases. Overexpression of c-erbB2 oncoprotein was detected in only 1 case. Vimentin was focally positive in 1 case. Two cases of intraductal spindle cell carcinoma and 1 of the 3 cases of invasive spindle cell carcinoma were classified as neuroendocrine carcinoma of spindle cell type, while the remaining 2 cases of invasive spindle cell carcinoma were considered as metaplastic carcinoma with neuroendocrine differentiation. Amongst the 4 patients with follow-up information available, 3 were still alive 24 to 58 months after the initial diagnosis. One patient died within 27 months of diagnosis. CONCLUSIONS: The presence of spindle tumor cells and sometimes intracytoplasmic mucin are useful morphologic clues in diagnosing spindle cell carcinoma of the breast with neuroendocrine differentiation. Intraductal neuroendocrine spindle cell carcinoma needs to be distinguished from usual ductal hyperplasia and intraductal papilloma. On the other hand, invasive spindle cell carcinoma with neuroendocrine differentiation needs to be distinguished from spindle cell myoepithelioma, malignant melanoma and sometimes soft tissue neoplasm.