A Biopsy Diagnosis? Clinical Clues and Patterns to Help Distinguish Cutaneous Metastases: Part II of II*
*Part I of this review ran in the June 2011 issue.
Specific Cutaneous Metastases
Breast
Breast cancer is the primary cancer for 70 percent of cutaneous metastases in women overall, and cutaneous lesions usually occur on the anterior chest.3 There are several distinct clinicopathologic variants of cutaneous disease, including carcinoma erysipelatoides, en cuirasse, telangiectaticum, alopecia neoplastica and Paget's disease, which have been previously discussed (see "Presentation and Clinical Patterns"). In addition, cutaneous metastatic breast cancer may present as nodular metastatic carcinoma and carcinoma of the inframammary crease. The nodular form may be solitary, but usually presents as multiple smooth, firm lesions. Some nodules may ulcerate, and some may be pigmented and thus mimic melanoma. Carcinoma of the inframammary crease usually occurs in women with pendulous breasts and resembles intertriginous dermatitis.21
Breast cancer is the primary cancer for 70 percent of cutaneous metastases in women overall, and cutaneous lesions usually occur on the anterior chest.3 There are several distinct clinicopathologic variants of cutaneous disease, including carcinoma erysipelatoides, en cuirasse, telangiectaticum, alopecia neoplastica and Paget's disease, which have been previously discussed (see "Presentation and Clinical Patterns"). In addition, cutaneous metastatic breast cancer may present as nodular metastatic carcinoma and carcinoma of the inframammary crease. The nodular form may be solitary, but usually presents as multiple smooth, firm lesions. Some nodules may ulcerate, and some may be pigmented and thus mimic melanoma. Carcinoma of the inframammary crease usually occurs in women with pendulous breasts and resembles intertriginous dermatitis.21
In general, the histopathology of cutaneous metastatic breast cancer is of a poorly differentiated adenocarcinoma with an invasive pattern of growth.10 There is variation with respect to the proportion of tumor cells and stroma, as there may be sheets of tumor cells in the dermis, or fewer cells arranged in a linear fashion between collagen bundles. In some instances, there may be so few tumor cells scattered in the dermis that it is difficult to distinguish carcinoma from an inflammatory infiltrate.1,9,10 When considering subtypes, invasive ductal carcinoma may demonstrate malignant ductal
epithelial cells arranged in sheets, cords or glands, while in lobular carcinoma, the cells are uniform, loosely cohesive and have regular nuclei. Tumor cells may be positive for estrogen
receptors, progesterone receptors, GCDFP-15, and CK7 among other markers.6
Lung
Lung cancer is the most common visceral tumor in men to metastasize to the skin and may be the first sign of an internal malignancy. Lung cancers can be classified into small cell and non-small cell carcinomas, which include squamous cell and adenocarcinoma.6 The latter two types each account for 30 percent of skin metastases from primary lung cancers, and undifferentiated tumors account for 40 percent.10 Squamous cell metastases are usually poorly differentiated with malignant cells arranged in a solid nesting pattern, and can be differentiated from primary squamous cell carcinoma of the skin by the absence of epidermal involvement.6,10 Adenocarcinoma metastases are moderately differentiated and have glandular features resembling primary lesions. Intracytoplasmic mucin can also be present.6,9 Undifferentiated tumors can histologically resemble lymphomas. They are usually derived from small cell lung carcinomas, which are anaplastic and contain cells with scant cytoplasm, hyperchromatic nuclei, dense core granules and clumped chromatin arranged in sheets, clusters or rosettes. This grouping of cells is less likely to occur in lymphoma, making small cell carcinoma the more likely diagnosis in undifferentiated tumors.6,10 Cutaneous lung metastases stain positive for thyroid transcription factor.
Lung cancer is the most common visceral tumor in men to metastasize to the skin and may be the first sign of an internal malignancy. Lung cancers can be classified into small cell and non-small cell carcinomas, which include squamous cell and adenocarcinoma.6 The latter two types each account for 30 percent of skin metastases from primary lung cancers, and undifferentiated tumors account for 40 percent.10 Squamous cell metastases are usually poorly differentiated with malignant cells arranged in a solid nesting pattern, and can be differentiated from primary squamous cell carcinoma of the skin by the absence of epidermal involvement.6,10 Adenocarcinoma metastases are moderately differentiated and have glandular features resembling primary lesions. Intracytoplasmic mucin can also be present.6,9 Undifferentiated tumors can histologically resemble lymphomas. They are usually derived from small cell lung carcinomas, which are anaplastic and contain cells with scant cytoplasm, hyperchromatic nuclei, dense core granules and clumped chromatin arranged in sheets, clusters or rosettes. This grouping of cells is less likely to occur in lymphoma, making small cell carcinoma the more likely diagnosis in undifferentiated tumors.6,10 Cutaneous lung metastases stain positive for thyroid transcription factor.
Gastrointestinal Tract
Esophagus. The frequency of cutaneous metastatis among patients with esophageal cancer varies in the literature, ranging from 1 percent (n=838 patients37) to 8.6 percent (n= 35 patients3). Metastatic lesions present as nodules that involve the head (especially scalp), neck and fingers.1,3 Squamous cell carcinoma, arising from the upper esophagus, is more common, but metastases from adenocarcioma do occur. Lesions are histologically similar to the primary lesions and stain positively for mucin.38
Esophagus. The frequency of cutaneous metastatis among patients with esophageal cancer varies in the literature, ranging from 1 percent (n=838 patients37) to 8.6 percent (n= 35 patients3). Metastatic lesions present as nodules that involve the head (especially scalp), neck and fingers.1,3 Squamous cell carcinoma, arising from the upper esophagus, is more common, but metastases from adenocarcioma do occur. Lesions are histologically similar to the primary lesions and stain positively for mucin.38
Stomach. Cutaneous metastases occur in 2 percent of patients with stomach cancer,3 but the incidence may be higher outside the U.S., particularly in Japan, where primary gastric carcinoma is more frequent.6 The most common sites of involvement include the head, neck, and abdomen, especially the umbilical region.3,16 Metastatic lesions may present as nodules, plaques, zosteriform lesions, carcinoma en cuirasse and carcinoma erysipelatoides.6,16 Epidermotropic metastases have also been reported.33 Cutaneous lesions most commonly arise from gastric adenocarcinoma, but mucinous carcinoma may also produce skin metastases.21 Tumor cells are localized to the middle and lower dermis and are usu-
