Chapter 36 Metastatic Carcinoma of the Skin Cutaneous metastases are of diagnostic importance because they may be the first manifestation of an undiscovered internal malignancy or the first indication of metastasis of a supposedly adequately treated malignancy. The cutaneous metastases in men revealed the following incidences of primary carcinoma: lungs, 24%; large intestine, 19%; oral cavity, 12%; and kidney and stomach, each 6%. Metastatic melanoma was found in 13%. The most common cutaneous metastatic cancer are from the lung, kidney, and ovary. Dissemination may take place through the lymphatics or the bloodstream. Cutaneous metastases are more likely to be found in older individuals.

Metastases tend to occur on cutaneous surfaces near the site of the primary tumor,. Metastasis to the umbilicus is common, and the underlying primary tumor is usually an adenocarcinoma of the stomach, ovaries, endometrium, or breast. In the metastasis of chest wall and abdominal wall, the most frequent site of the primary tumor are the breast, ovary, lung, prostate, bladder, or stomach. Distinction of a primary carcinoma of the skin from a metastatic lesion can be a problem when dealing with a solitary lesion. Some examples include primary mucinous adenocarcinoma of skin, adenocarcinoma of the mammary-like glands of the vulva , cutaneous signet-ring carcinoma, primary carcinoids, and adnexal carcinomas.

To establish a diagnosis of a primary mucinous carcinoma of the skin, the presence of a peripheral myoepithelial layer, if present, is helpful. Immunoperoxidase positivity with CD15, CK5/6, and 34BE12 (22) favor a primary lesion. P63 staining of a tumor favors a primary tumor over a metastatic lesion. Although metastatic lesions can occur at any site, the scalp, head, and umbilicus are more frequent. Finding of the primary tumor or the presence of serum chromogranin would indicate a metastatic carcinoid Some immunoperoxidase studies that are helpful indistinguishing primary tumors from metastatic lesions.

Some immunoperoxidase studies that are helpful in distinguishing primary tumors from metastatic lesions. FIGURE 36-1. Metastatic carcinoma of stomach origin to the face. Multiple dermal and subcutaneous nodules are seen on the face and neck.

Histopathology :In inflammatory carcinoma, histologic CARCINOMA OF THE BREAST Cutaneous metastases that occur predominantly by lymphatic dissemination include inflammatory carcinoma, carcinoma en cuirasse, telangiectatic and nodular carcinoma, and carcinoma of the inframammary crease. Alopecia neoplastica and mammary carcinoma of the eyelid are probably caused by hematogenous spread. Histopathology :In inflammatory carcinoma, histologic examination of the skin reveals extensive invasion of the dermal and subcutaneous lymphatics by groups of tumor cells.. The tumor cells are atypical in character with large, pleomorphic, hyperchromatic nuclei. Capillary congestion, which is the reason for the clinical appearance of erythema and warmth

IGURE 36-4. Metastatic breast carcinoma IGURE 36-4. Metastatic breast carcinoma. Cords of atypical cells with ill-defined attempts at acinus formation infiltrating between collagen bundles. FIGURE 36-3. Metastatic breast carcinoma. Individual atypical tumor cells and infiltrate are seen between fibrotic collagen bundles

The tumor cells often lie singly, in/single rows between fibrotic and thickened collagen bundles In telangiectatic carcinoma, the tumor cells tend to be located more superficially in the dermis within dilated lymphatic vessels than those in inflammatory carcinoma. In nodular carcinoma, there are variably sized groups of tumor cells in the dermis, and these nodular areas are surrounded by fibrosis. Sometimes, a nodule may be pigmented and clinically suggestive of a melanoma or pigmented basal cell carcinoma. Epidermotropic involvement from metastatic breast carcinoma may mimic malignant melanoma and/or Paget’s disease.

The signet-ring cell histologic pattern of breast carcinoma may also be seen in carcinoma of the gastrointestinal tract and urinary bladder FIGURE 36-5. Metastatic breast carcinoma. This tumor demonstrates a signet-ring cell pattern.

Immunoperoxidase Studies: Cutaneous metastases are positive with most cytokeratins, except for CK20 , and often are positive with epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). CK7 is positive in the majority of cases of carcinoma, with the exception of those arising from the colon, prostate, kidney, thymus, carcinoid tumors of the lung and gastrointestinal tract, and Merkel cell tumors of the skin. CARCINOMA OF THE LUNG: Metastasis to the skin is more common in men , than in women. Metastases may occur on any cutaneous surface, but the most common sites are the chest wall and posterior abdomen . Oat cell carcinoma shows predilection for the skin of the back

Histopathology: Cutaneous metastases were undifferentiated in approximately 40% and adenocarcinoma and squamous cell carcinoma in approximately 30% each FIGURE 36-6. Metastatic carcinoid tumor from the lung. Uniform small cells without high-grade atypia, forming nests in a typical pattern of a carcinoid tumor.

Carcinoid tumors of the lung are derived from the bronchus and consist of solid islands and nests of uniform cells. Squamous cell carcinomas that are metastatic to skin are usually poorly or moderately differentiated. GASTROINTESTINAL CARCINOMA : Carcinoma of the colon and rectum is the second most common type of primary cancer in men. Histopathology. Most cutaneous metastases from the large intestine and all from the stomach were adenocarcinomas. Signet-ring cell differentiation is not usually seen in lesions from the large intestine but may be present in lesions from the Stomach . Alcian blue positive at pH 2.5 and negative at pH 0.4, and aldehyde-fuchsin positive at pH 1.7 and negative at pH 1.0.

Immunoperoxidase Studies Immunoperoxidase Studies. CK20 positivity in almost all colorectal carcinomas and Merkel cell tumors, pancreatic carcinomas (62%), gastric carcinomas (50%), cholangiocarcinomas (43%), transitional cell carcinomas. FIGURE 36-8. Metastatic carcinoma from colon, cytokeratin-20. A, B: CK20 reactivity, usually studied in coordination with that of CK7, helps to distinguish this lesion from a nongastrointestinal tract adenocarcinoma. Bladder and mucinous ovarian carcinomas may also be positive.

FIGURE 36-7. Metastatic carcinoma from the colon FIGURE 36-7. Metastatic carcinoma from the colon. This tumor shows secondary epidermal involvement (A) and is comprised of somewhat irregular but relatively well-formed glands (A,B).

ORAL CAVITY CARCINOMA Most lesions metastasizing from carcinomas of the oral cavity are spread by lymphatic invasion and are located on the face or neck . They usually appear as multiple or solitary nodules and sometimes are ulcerated. Histopathology. The lesions are almost always squamous cell in type and are usually moderately or well differentiated, located usually in the deeper dermis and subcutaneous tissue with sparing of the superficial cutis. RENAL CELL CARCINOMA In renal cell carcinoma, tumors are most commonly located in the head and neck area. They often present as solitary or a few nodules and may be skin colored, reddish, or violaceous.

The tumor cells show oval nuclei with abundant, clear cytoplasm and often are in a glandular configuration, and extravasated red blood cells are frequent. FIGURE 36-9. Metastatic carcinoma from kidney. A dermal tumor pressing on and elevating the overlying epidermis (A) and comprised of clear cells with prominent capillaries in the stroma (B). Renal cell carcinoma marker (RCC-Ma) is positive

CARCINOMA OF THE OVARY: In carcinoma of the ovary, the most frequent sites involved are the abdomen, including the umbilicus, vulva, or back Histopathology. The features are usually of a moderately or well-differentiated adenocarcinoma, often having a papillary configuration and containing psammoma bodies. Immunoperoxidase Studies. CK7 positive and CK20 negative FIGURE 36-10. Metastatic mucinous ovarian carcinoma. Infiltrating acinar structures with scattered signet cells.

CARCINOID AND NEUROENDOCRINE CARCINOMAS Histopathology CARCINOID AND NEUROENDOCRINE CARCINOMAS Histopathology. Carcinoid metastases in the skin and subcutaneous tissue consist of solid islands, nests, and cords of tumor cells. As a rule, the cells appear quite uniform in size and shape; have small, rounded nuclei; and abundant, clear, or eosinophilic cytoplasm Immunoperoxidase and Electron Microscopy Studies: Immunoperoxidase studies are of great value in distinguishing a primary Merkel cell carcinoma of the skin from a metastatic neuroendocrine carcinoma. Merkel cell carcinomas are usually positive with CK20 and are negative with TTF-1 and CK7

MISCELLANEOUS CARCINOMAS In metastatic carcinoma from the liver, the arrangement of malignant hepatocytes in irregular columns is fairly distinctive, and if there are acinar structures containing bile, the diagnosis is definite In choriocarcinoma, the cutaneous metastases show the two types of cells that arise from the fetal trophoblast: cytotrophoblasts and syncytiotrophoblasts. Metastatic carcinoma of the prostate to the skin is rare, reactivity with prostate-specific antigen establishes the diagnosis. Pancreatic cancer metastatic to the skin is rare,the most common site is the umbilical area. Histologically:, It usually represents an adenocarcinoma. Immunoperoxidase : with a carbohydrate antigen (CA19-9) may be positive

Medullary, follicular, and papillary thyroid carcinomas may retain their histologic patterns in the cutaneous metastases. Immunoperoxidase studies often show a positive reaction to antithyroglobulin antibody and TFF-1 FIGURE 36-11. Metastatic carcinoma from thyroid. In this example of a metastatic follicular carcinoma, comprised of small epithelial cells forming ill-defined follicles containing pink colloid, there is little atypia, and the lesion could not be distinguished from a follicular adenoma except for its metastatic location.