Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.     

HER-2/neu expression in extramammary Paget disease: a clinicopathologic and immunohistochemistry study of 47 cases with and without underlying malignancy

Extramammary Paget disease (EMPD) is an infrequent skin cancer sometimes representing a secondary event caused by extension of an underlying carcinoma. Her-2/neu overexpression in breast cancer is correlated with a more aggressive behavior, but anti-Her-2/neu therapy improves survival in these patients. We investigated Her-2/neu expression by immunohistochemistry in cases of EMPD with and without underlying malignancy to try to correlate with tumor recurrence, progression and possible targeted therapy. Forty-seven cases were analyzed (6 from the scrotum, 7 perianal region, 1 axilla and 33 vulva). Two cases had invasive EMPD (one from vulva and one from scrotum). The overall Her-2/neu expression was 31.9%. Of the noninvasive EMPD of the vulva (32 cases), Her-2/neu was shown in 38%. The case of invasive vulvar EMPD was negative. All six scrotal EMPD lacked Her2/neu expression. Her-2/neu was expressed in two of seven perianal cases (33.3%). The EMPD on the axilla (one case) was negative. Eighteen cases had recurrence, and of these, 44.4% expressed Her-2/neu in the initial lesion. A high proportion of EMPD showed Her-2/neu expression (31.9%), indicating that these patients may benefit from targeted therapy. The proportion of positive cases was higher in lesions that had recurred at last follow up (44.4%), suggesting a more aggressive behavior.     

Sister Mary Joseph nodule: a case report

A metastatic malignancy of the umbilicus is commonly termed Sister Mary Joseph nodule (SMJN). It is a rare occurrence but may represent the first sign of a visceral malignancy and therefore should prompt a thorough search for the primary tumor. Typically, the most common origin of an umbilical metastasis is an adenocarcinoma from a gastrointestinal or gynecologic primary malignancy. The presence of SMJN carries a poor prognosis with the average survival time at the appearance of an umbilical metastasis being 10 months. We report a case of a 66-year-old man who was referred for evaluation of an enlarging umbilical lesion. Histopathology revealed adenocarcinoma. After a full metastatic workup, the tumor of origin was identified as adenocarcinoma of the sigmoid colon. Benign tumors of the umbilicus are uncommon. This case report serves to emphasize the importance of obtaining a histologic diagnosis when any new lesion presents in the umbilical region.     

A case of Sister Mary Joseph's nodule from prostatic cancer

The metastasis of a visceral malignancy to the umbilicus is known as "Sister Mary Joseph's nodule" (SMJN). We recently encountered an 80-year-old man in whom umbilical metastasis of prostatic cancer was revealed during the course of treatment. The lesion was a red, firm, elastic nodule, 2.5 cm in diameter, with a bumpy, irregular surface, but without subjective symptoms. In histopathological examination, atypical cells with intensely stained, small quasi-circular nuclei and weakly eosinophilic cytoplasm were found in all layers of the dermis. In some parts of these tumor cells, a gland-like structure was observed. Immunohistochemical investigation of the invading tumor cells disclosed immunoreactivity for prostate specific antigen and prostatic acid phosphatase, supporting a diagnosis of SMJN from prostatic cancer. His general condition gradually deteriorated, and he died 2 months later. Prostate cancer often metastasizes to bones and lymph nodes, but rarely to the skin. Of all the cases of cutaneous metastasis of prostate cancer reported in Japan, only three metastases have occurred to the umbilical region. The present case is therefore an example of a very rare condition.     

Trastuzumab/docetaxel-induced nail dystrophy

Combination of trastuzumab, an antibody directed against the Her-2/neu receptor, with chemotherapy is increasingly used for the treatment of metastatic breast cancer, and currently is being explored in the adjuvant setting. We report the case of a 55-year-old woman with metastatic breast cancer, who developed nail dystrophic changes comprising Beau's lines, subungual hyperkeratosis, dyschromia and onycholysis early in the treatment with trastuzumab/docetaxel. Nail alterations advanced with the continuation of therapy. This combination of nail changes, and its progressive course, are extremely rarely encountered with the use of taxanes alone. The cellular mechanisms of action of trastuzumab and docetaxel are discussed in regards to their potential synergy, which may explain the particularities and severity of nail alterations in this patient.     

Cutaneous metastasis to the chest wall from prostate cancer

Prostate cancer is the most common malignancy in men in the United States. However, skin metastasis from prostate carcinoma is extremely uncommon. Here, we present a 75-year-old Caucasian man with a history of metastatic prostate cancer developing multiple subcutaneous, erythematous nodules over the left anterior chest over a 3-month period. A fine needle aspiration of a subcutaneous nodule showed neoplastic cells consistent with metastatic prostate cancer. This case represents only the fourth reported case of cutaneous metastasis from prostate cancer to the chest wall and the ninth case outside the inguinal area.     

Primary signet ring cell carcinoma of the eyelid: report of a case demonstrating further analogy to lobular carcinoma of the breast with a literature review.

Primary signet ring cell carcinoma of the eyelid is a rare neoplasm with less than ten cases described. This report details another case, which shows further parallels to lobular carcinoma of the breast, and reviews the literature on this subject. A 73-year-old white female presented with diffuse induration of her left eyelids. Histopathology revealed a delicate infiltrate of epithelial cells scattered throughout the lid stroma in a non-destructive pattern. The cells were relatively monomorphous and showed only mild atypia and rare mitotic figures. Many had slightly granular amphophilic cytoplasms, others showed distinct signet ring cell morphology, and all were strongly positive for epithelial mucin. Immunomicroscopy showed strong reactivity for estrogen receptor (ER), progesterone receptor (PR) and gross cystic disease fluid protein-15 (GCDFP-15), and was negative for Her-2/neu (erb-2) and cytokeratin 20. An extensive workup for other primary sites was negative. Orbital exenteration showed extensive involvement of both lids and soft tissue, including diffuse muscle and lacrimal gland infiltration. In the breast, signet ring cell carcinoma is considered a variant of lobular carcinoma. The delicate infiltrating pattern in our case and the ER+, PR+, GCDFP-15+, Her-2/neu-phenotype further strengthen this analogy. Together, these data also support apocrine differentiation of primary eyelid signet ring cell carcinoma.     

Sister Mary Joseph's nodule: a clue to finding pancreatic cancer in a patient previously affected by gastric cancer

An 82-year-old man with Sister Mary Joseph's nodule (SMJN) is reported. He had a past history of gastric cancer, which had been removed in its early stage. Histopathological findings, in which CA19-9 and other markers, such as PCNA and p53, were strongly positive in SMJN but negative in specimens from the gastric cancer, suggested that the nodule had derived from another internal malignancy and a detailed search led to the discovery of a pancreatic cancer.     

Umbilical metastasis from carcinoma of the stomach. Sister Joseph's nodule.

A patient had umbilical metastasis from a carcinoma of the stomach. The umbilical lesion (Sister Joseph's nodule) is a characteristic sign of metastatic tumor, and the diagnosis was confirmed by biopsy. The cutaneous metastasis was associated with visceral metastases.     

Sister Mary Joseph结节一例

患者,男,52岁。脐部结节8个月。脐部皮损组织病理诊断为皮肤转移性腺癌(Sister Mary Joseph结节),免疫组化染色：细胞角蛋白(CK)20阳性、CK7阴性、尾型同源框转录因子-2(CDX2)阳性。肺部CT示肺转移癌。诊断：Sister Mary Joseph结节。     

Sister Joseph's Nodule: A Case Report and Review of the Japanese Literature

We report a case of metastatic carcinoma on the umbilicus, which is known as Sister Joseph's nodule. A 65-year-old man with the chief complaint of a painful nodule on the umbilicus was refered to our hospital. Histopathological examination revealed moderately differentiated tubular adenocarcinoma in the dermis. Endoscopic examination found gastric cancer of Borrmann type IV. The umbilical lesion represented a metastasis from the gastric cancer. We reviewed 80 cases of metastatic carcinomas to the umbilicus that have been reported in the Japanese literature.     

Basaloid large cell lung carcinoma presenting as cutaneous metastasis at the colostomy site after abdominoperineal resection for rectal carcinoma

The occurrence of a tumor at the colostomy site after abdominoperineal resection for rectal carcinoma is rare and it may be related to a previously resected carcinoma or another primary tumor. We report a 61‐year‐old man who developed an ulcerated skin nodule at her colostomy site 6 years after resection of a rectal adenocarcinoma. Histopathologically, the skin nodule was composed of atypical large and pleomorphic cells with high mitotic rate and they were arranged in nests and within lymphatic channels in the dermis. The neoplastic cells were immunoreactive for cytokeratin (CK) AE1/3, CK7, CK34ßE12, epithelial membrane antigen and vimentin while detection of human papillomavirus and Epstein–Barr virus DNA was negative. A diagnosis of basaloid large cell carcinoma of pulmonary origin was suggested and it was confirmed by computed tomography‐guided fine needle aspiration of a right subpleural mass. A metastatic tumor at the colostomy site is an exceptional finding and may be the first manifestation of lung cancer, especially if it consist of pleomorphic large cells with high mitotic rate and basaloid immunophenotype.     

Sister Mary Joseph结节

报告1例可能为胃癌转移的Sister Mary Joseph结节1例.患者男,44岁.脐部出现暗红色大小不等的结节7个月.皮损组织病理检查:真皮全层胶原束间散在呈腺样分化的肿瘤细胞,免疫组化染色:癌胚抗原(CEA)阳性、细胞角蛋白(CK)20阳性、CK7阳性、甲状腺转录因子(TIT)-1阴性.糖链抗原(CA)19-9、CA72-4、CA24-2均升高.腹部B超检查示:胃幽门部胃壁增生性病变,肝右叶多发偏强回声结节,腹水.     

Epidermotropic metastatic prostate carcinoma presenting as an umbilical nodule-Sister Mary Joseph nodule

Carcinoma of the prostate accounts for fewer than 1% of all skin metastases. Cutaneous metastases from prostate carcinoma most often involve the penis, the anterior aspect of the thighs, the suprapubic area, and the perineum, but they also have been reported in the scalp, the chest, the back, and even the face. We report an unusual case of metastatic prostate adenocarcinoma that presented as an umbilical nodule (Sister Mary Joseph nodule) and demonstrated significant epidermotropism histologically. A review of the literature has found only one documented case of prostatic carcinoma metastasizing to the umbilicus, and one other documented case of epidermotropic metastatic prostate carcinoma.     

Breast Cancer Cutaneous Metastasis at Core Needle Biopsy Site

Cutaneous metastasis from breast cancer can occur by direct invasion, lymphatic and vascular spread as well as iatrogenic implantation. Metastasis that occurs by iatrogenic implantation after needle biopsy is very rare but the potential risk must be considered. In this report, we describe a case of breast cancer cutaneous metastasis that occurred by iatrogenic implantation following core needle biopsy. A 53-year-old woman presented with a 1×1 cm sized erythematous nodule at the biopsy site after breast conserving surgery for primary cancer. Histopathological findings confirmed cutaneous metastasis. The possibility of this consequence must be considered when performing needle biopsies.     

Skin metastasis in laryngeal carcinoma

Cutaneous metastases from carcinoma of the larynx are very rare. We observed a 64-year-old Japanese patient with squamous cell carcinoma of the larynx who developed a subcutaneous nodule on the abdomen. It was found to be a metastatic tumour from the laryngeal cancer, histopathologically as well as histochemically.     

CUTANEOUS PANCREATIC METASTASIS: A CASE REPORT AND REVIEW OF LITERATURE

Pancreatic cancer is one of the most dangerous human cancers and will continue to be a major unsolved health problem as we enter the 21^st century. This is the case despite advances in imaging technology and surgical management. Indeed, 80% to 90% of pancreatic cancers are diagnosed either at the locally advanced or metastatic stage. Cutaneous metastases originating from pancreatic cancer are relatively rare. The most common site of cutaneous metastasis is the umbilicus, and this is known as the Sister Joseph''s nodule. Very few patients have been reported with cutaneous lesions disclosing a pancreatic carcinoma at sites other than the umbilical area. To the best of our knowledge, there have been no previous reports on cutaneous pancreatic metastasis in Egypt. This is a report on a patient with cutaneous pancreatic metastases at the neck and review of reported non-umbilical cutaneous metastases from pancreatic carcinoma in the literatures.     

Clinical manifestations of cutaneous metastases: a review with special emphasis on cutaneous metastases mimicking keratoacanthoma

Approximately 5% of oncology patients develop cutaneous metastases, with only a small number of these patients (less than 1%) having metastatic skin lesions as the first sign of their visceral cancer. Metastases tend to occur on skin surfaces in the vicinity of the primary tumor. However, any site may be affected by cutaneous metastases. Skin metastases can present with several morphologies including, albeit rarely, keratoacanthoma-like lesions. Keratoacanthoma is a keratinous tumor that morphologically appears as a nodule with a central keratin-filled crater. This article reviews the characteristics of oncology patients whose cutaneous metastases mimicked a keratoacanthoma, including illustrations from our patient, a 53-year-old Caucasian man whose metastatic esophageal adenocarcinoma not only presented with a keratoacanthoma-like tumor on his upper lip but also a forehead macule and a scalp nodule. We also report keratoacanthoma-like presentations from literature cases of breast cancer, chondrosarcoma, and pulmonary malignancies. The lesions were discovered 3-24 months after diagnosis of visceral cancer and led to the discovery of unsuspected lung cancer in two patients. Most of the patients (60%) died within 2 months of discovery of the keratoacanthoma-like cutaneous metastases. We also reviewed the literature and discuss other morphologies of cutaneous metastases in patients whose primary tumors were in the breast, lung, and esophagus. In addition, we review from the literature other examples of tumors that present as metastatic nodules on the scalp. The possibility of cutaneous metastasis should be entertained and pathologic evaluation should be considered in an oncology patient with underlying visceral malignancy who develops a keratoacanthoma-like lesion.     

Papillary thyroid carcinoma metastasis most probably due to fine needle aspiration biopsy. A case report

Implantation of cancer cells from needle biopsy has been reported in a wide range of malignancies. Fine needle aspiration biopsy has become an accepted method for assessment of thyroid nodules. Local reappearance of thyroid cancer from needle track dissemination is a rare complication of thyroid aspiration. A 45-year-old female developed local recurrence of papillary thyroid carcinoma four years after aspiration biopsy and thyroidectomy. Metastatic deposits appeared in the skin and the sternocleidomastoid muscle. The linear array and the site of metastases implied that seeding most probably resulted from the needle biopsy.     

Cutaneous metastases: A great imitator

Neoplastic cells originating from a primary cancer can uncommonly spread to the skin, where they suggest a poor prognosis for the patient. In women, melanoma, breast, ovarian, oral cavity, and lung are the most common primary sources; in men, melanoma, lung, colon, and squamous cell carcinoma of the head and neck predominate. The classic presentation of cutaneous metastases is a firm, painless, flesh-colored to an erythematous dermal nodule (or nodules); however, several other presentations, including inflammatory, cicatricial, and bullous lesions, have been reported. Cutaneous metastases may also mimic benign conditions such as lipomas, hemangiomas, or cellulitis. A high degree of clinical suspicion is necessary, and the diagnosis is confirmed by biopsy, which may also be used to establish the primary malignancy if unknown, as the histopathologic appearance of the metastatic tissue may mimic the primary tumor. Treatments include excision of the metastases, chemotherapy, immunotherapy, radiation, and/or palliative care.