Cutaneous Metastasis from Signet-ring Gastric Adenocarcinoma in a Carcinoma En Cuirasse Pattern: An Unusual Clinical-diagnostic Sequence.

Cutaneous metastasis (CM) of gastric adenocarcinoma (ADC) is rare and usually presents late in the course of the disease. We report a rare case of carcinoma en cuirasse (CEC) pattern of CM secondary to gastric malignancy in a 55-year-old male patient-the interesting part being that CM was the first-presenting sign, which on further histopathological and immunohistochemical evaluation led to the diagnosis of hidden gastric carcinoma. The finding of signet ring cells (SRCs) on cutaneous biopsy further added a differential of the rare possibility of primary cutaneous tumors.

What was known?

CMs of internal malignancies are a well-known entity. They most commonly arise from lung, colon, melanoma, and breast cancer. They can present in one of the three main forms: Nodular; sclerodermoid [carcinoma en cuirasse (CEC)]; and inflammatory (carcinoma erysipeloides) cancer. CEC is a rare presentation, secondary to breast cancer in the majority of the cases. Signet-ring cell (SRC) appearance is a characteristic histopathological finding, which in skin can imply which in skin can imply either, a primary or a secondary.

Introduction

Cutaneous metastasis (CM) of internal malignancies is an uncommon manifestation, estimated to present in 0.6-10.4% of patients and representing 2% of all skin tumors.[1] The most common origins of CM in males; are reported from lung, colon, melanoma, squamous cell carcinoma of the oral cavity, and renal cell carcinoma and in females; breast, colon, melanoma and ovarian cancer.[2] They usually occur late in the course of the disease. Rarely, in about 0.5-1% cases, they may be the first indication of an internal neoplasm, and in such cases the most common sources are from the kidney, lung, thyroid, and ovary.[2] CM from gastric carcinoma is rare, with a reported frequency of 6% and 1% of all skin metastases in males and females, respectively.[3] This sort of rarity can lead to misdiagnosis of skin lesions, especially when CM predates the diagnosis of visceral malignancy.

We report an unusual clinical-diagnostic sequence of a patient presenting with a very rare carcinoma en cuirasse (CEC) pattern of CM over the abdominal skin. The lesions showed signet-ring cell (SRC) infiltration on histopathology, bringing to the forefront a previously undiagnosed gastric carcinoma.

Case Report

A 55-year-old man presented with a 3-month history of redness and thickening of the skin around the umblicus. The patient gave a history of vague gastrointestinal symptoms including nausea and anorexia for 4 months before the appearance of skin lesions, and a recent, unquantified weight loss and fatigue. There were no complaints of dysphagia, hematemesis, or melena. A history of difficulty in micturition was also elicited. Clinical examination revealed two well-defined erythematous to brown leathery plaques measuring approximately 15×20 cm and 15×8 cm over the right and left abdominal flanks, respectively. A pink-colored polypoidal growth was present over the right indurated plaque [Figure 1]. On palpation, the skin was unpinchable and a nontender, woody, hard induration was present. The systemic examination was normal. No mass was palpable per abdomen. Tender bilateral inguinal lymphadenopathy was present.

Figure 1

CM over the abdomen in a CEC pattern

Routine hematological and biochemical investigations were within normal limits except for a low hemoglobin level of 7.4 g/dL and a raised erythrocyte sedimentation rate of 42 mm/h.

The skin biopsy showed a normal epidermis and infiltration of the dermis by inflammatory cells along with small mononuclear cells (SRCs) with a monocytoid appearance, at places present in the “Indian filing” pattern [Figure 2a]. The appearance was that of a mucin-producing adenocarcinoma (ADC), metastatic to skin. The mucin-producing SRCs were diastase-resistant periodic acid-Schiff (PAS)- and mucicarmine-positive, suggesting gastric origin. On immunohistochemistry, tumoral cells were positive for cytokeratins [Figure 2b] and epithelial membrane antigen (EMA) [Figure 2c], and negative for estrogen and progesterone receptor (ER/PR), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), leukocyte common antigen (LCA), and the melanocytic markers S100 and HMB45.

Figure 2

(a) [Hematoxylin and eosin (H and E), ×20]. Skin biopsy specimen showed infiltration of the dermis by inflammatory cells along with scattered signet ring-shaped tumor cells (b) (H and E, ×20). Immunohistochemically: SRCs presented positivity for cytokeratin (c) (H and E, ×10). Immunohistochemically: SRCs presented positivity for EMA

Abdominal ultrasonography showed a mural thickening of the stomach of size 12 mm and a cystic focus 15×17 mm in the prostrate. Endoscopic findings revealed an ulcerative growth of size 15×20 mm on the lesser curvature of the stomach. On the basis of immunohistochemical findings, gastric biopsy was planned, which unexpectedly revealed monocytoid cells similar to the findings observed on cutaneous biopsy, suggesting a moderately differentiated SRC carcinoma. Computed tomography of the abdomen showed an extensive edema of the subcutaneous tissue, periumbilically in the midabdomen, consistent with a carcinomatous lymphangitis. It also revealed the presence of metastatic nodules in the prostrate, bladder, mesentery, and retroperitoneal and peripancreatic lymph nodes.

The patient was referred to oncologists for the management of metastatic cancer of gastric origin and started on chemotherapy.

Discussion

The presence of SRCs in skin can imply either a primary or a secondary malignancy. These cells are so named because an inclusion or accumulation crescentically distorts the nucleus to the cellular border, resulting in a signet-ring appearance.[4] Cutaneous neoplasms that may contain SRCs include squamous cell carcinoma, basal cell carcinoma, primary cutaneous SRC carcinoma of eccrine or apocrine origin, melanocytic tumors (nevi or melanomas), liposarcomas, hydradenomas, cylindromas, lymphomas, and the atrophic variant of mycosis fungoides.[4] However, before diagnosing a primary tumor, it is very important to rule out any primary visceral malignancy with SRC differentiation that has metastasized to the skin. The most probable origins for this are the mucous-producing carcinomas of the gastrointestinal tract (stomach, colon, rectum, cecal, appendix) and breast, and, less frequently, lung, bladder, prostate, endometrium, and esophagus.[5] The metastatic lesions can be distinguished from primary cutaneous neoplasms consisting of SRCs by the cytoplasmic accumulation of mucin in the former. The mucin-producing SRCs from gastric carcinoma characteristically stain with PAS and PAS-diastase.[4] Appropriate immunohistochemical staining further assists in making a definitive diagnosis.[4] Gastric carcinomas are classified histopathologically into papillary, tubular, mucinous, and SRC carcinomas (8.7%).[6] They usually metastasize to the regional lymph nodes, peritoneum, liver, pancreas, colon, lung, ovary, and bones, but metastasis to the skin is not commonly seen, occurring only in 0.8% of all gastric cancers.[78] CM can occur as a result of lymphatic or hematogenous dissemination of a tumor, or by direct infiltration. The preferential ability of certain cancer cells to metastasize to the skin may involve skin homing by chemokine receptors CCR10 and CXCR4.[9] CMs usually appear several months or years after the diagnosis of the primary tumor, and only in exceptional cases are they a presenting sign of the neoplastic process.[10]

CM can have a wide spectrum of presentations and is broadly divided into three groups: Nodular; sclerodermoid (CEC); and inflammatory (carcinoma erysipeloides).[10] Among the three types, subcutaneous or intradermal nodules represent the typical cutaneous manifestation of metastasized gastric cancer.[3] CEC was first described by Velpeau in 1838, as an “encasement of armor” because of its resemblance to the metal breastplate of a cuirassier (cavalry soldier).[11] It is characterized by extensive thickening, edema, and fibrosis of the dermis and subcutis, giving a sclerodermoid appearance.[12] It is a dramatic presentation of CM seen in only 0.7-9% of cases of breast cancer.[11] Very rarely it can be seen from carcinoma stomach, with only a few cases reported in the world literature.[13]

The occurrence of CM is usually an indicator of disseminated disease. However, with advancement in novel therapies that prolong survival, the prompt recognition of CM can help greatly in decreasing morbidity and mortality.

Conclusion

Our case was remarkable because of the rarity of CM (with CEC) of signet-ring gastric ADC and CM being the initial manifestation of the internal malignancy. Noting the distinction between primary and metastatic tumors of skin is highly important, due to the distinct management approaches needed for the two entities. Suspected patients should be subjected to histopathological and immunohistochemical studies. In a previously diagnosed tumor, the detection of CM can change the staging, prognosis, and treatment of the patient. CM can also herald a cancer recurrence after treatment of a primary tumor. In this scenario, the dermatologist plays a fundamental role and should always be attentive to such a diagnostic possibility.

What is new?

The carcinoma en cuirasse (CEC) pattern of cutaneous metastasis (CM) can very rarely be seen secondary to carcinoma stomach, with only a few cases reported in the world literature. Also, the histopathological finding of signet ring cells (SRCs) in association with this pattern has not been reported earlier.