An 86-Year-Old Woman With Gastric Outlet Obstruction

An 86-year-old woman was admitted to the hospital with a 2-month history of right upper quadrant pain, early satiety with vomiting, and weight loss. An endoscopy several days prior to her presentation had shown a gastric outlet obstruction; mucosal biopsies were negative for malignancy. Her medical history was significant for breast cancer on her left side, which had been treated by breast-conserving surgery and extended field irradiation. She had been clinically free of disease for 7 years. A computed tomographic scan of the abdomen and pelvis, upon her admission to the hospital, noted marked antral thickening. Endoscopie ultrasound showed a gastric outlet obstruction and diffuse gastric wall thickening within the antrum, observations that produced concern about a possible infiltrating malignant process. A small pocket of perihepatic ascites was visualized by endoscopie ultrasound, and 4 mL of serosanguinous fluid was aspirated and sent for cytologie examination. Repeat mucosal biopsies revealed chronic gastritis.

The smears prepared from the peritoneal fluid showed a poorly cohesive, monomorphic population of small-tomedium cells, predominantly single, admixed with scattered erythrocytes (Figure 1). The cells had scant, ill-defined cytoplasm and an increased nuclear-to-cytoplasm ratio. The nuclei were round and centrally located, with a fine chromatin pattern and occasional small nucleoli. Anisonucleosis was minimal (Figure 2). The cells were strongly immunoreactive for cytokeratin 7 (results not shown) and estrogen receptor (Figure 3), and mucicarmine stain highlighted occasional punched-out vacuoles in the cytoplasm (see arrow, Figure 4). Immunohistochemical stains for calretinin, Wilms tumor 1, gross cystic disease fluid protein, cytokeratin 20, SlOO, and leukocyte common antigen were negative.

What is your diagnosis?

Pathologic Diagnosis: Metastatic Lobular Carcinoma of the Breast With lntraperitoneal Carcinomatosis

Abstract

The cytologie diagnosis of metastatic carcinomas in body fluids is challenging when the malignant cells occur singly, have bland morphologic features, and represent the predominant population of cells. We present the case of a metastatic lobular carcinoma of the breast, identified in the ascites fluid in a patient without clinical signs of a recurrent neoplasm. Differential diagnoses range from benign to malignant entities and include neoplasms of diverse origins. Clinical history and immunohistochemical workup play important roles in the characterization of these cells. Their identification is of extreme importance, especially for patients without a personal history of a well-documented malignancy.

This case reflects the difficulty in distinguishing reactive mesothelial cells from other neoplastic cells in fluids. The single-cell pattern and the bland cytologie features present in this case are commonly found in benign processes, as well as in mesotheliomas, adenocarcinomas, lymphomas, and even some malignant melanomas. The interpretation of this effusion specimen is a challenge, because of the tremendous degree of cytologie overlap that can be present, not only between benign and reactive processes but also between malignancies of diverse origins.

Reactive changes in mesothelial cells can be observed in cirrhosis, radiation, chemotherapy, traumatic irritation, and chronic inflammation. Mesothelial cells can assume a highly variable appearance in both their nuclear and cytoplasmic morphology. They can present as a single population of cells with abundant, optically dense cytoplasm, with or without small perinuclear vacuoles. The nucleus is central or paracentral, and occasional multinucleation and significant variability in nuclear size and morphology may be encountered. Although characteristic of mesothelial cells, the appearance of slitlike spaces (so-called windows) between the cells is not specific and can be observed in other pathologic processes as the result of cellto-cell apposition with trapped secretions or because of fluid trapped between the cells (eg, malignant melanoma, adenocarcinoma).1

Mesotheliomas can present in effusions as highly cellular, bloody specimens, with cells maintaining the mesothelial morphology. Distinguishing benign cytologie atypia from malignant mesothelial proliferation can be a dilemma, because mesotheliomas can be bland, while reactive processes can be markedly atypical. The cells in mesothelioma present as uniform populations of cells arranged singly or in large aggregates, forming proliferative cell balls with scalloped edges or true papillary clusters. Variations in size, multinucleation, prominent nucleoli, and cell-in-cell arrangements ("cannibalism") are features that suggest malignancy. The use of a panel of antibody markers is of utmost importance when attempts are made to reliably distinguish mesothelioma from adenocarcinoma. The absence of immunohistochemical marking for calretinin and Wilms tumor 1 in our case suggests that the cells present in this effusion were not mesothelial cells.

Gastric carcinoma, especially the diffuse form, is an important clinical consideration. Signet-ring cell carcinomas are infiltrative, can metastasize to the peritoneum, and can be present in the ascites fluid as large signet-ring cells, with prominent intracytoplasmic vacuoles that compress the nucleus to the periphery. The small-to-medium cells present in this case, as well as the strong positive staining for estrogen receptor and the 2 negative gastric biopsies, argue against a gastric origin for these cells.

Effusions developing secondary to malignant melanoma are uncommon, with melanoma found in only 2% to 3% of malignant effusions.2 The morphologic diagnosis of melanoma in effusions might be difficult because of the wide variety of different cellular patterns and the absence of the principal identifying features, such as macronucleoli and melanin pigment, which are not always present.

Serous effusions are a common complication of lymphomas, and the malignant cells do not exhibit true cohesion on smear preparations. Lymphoma seldom presents with effusions without a known history of malignancy, and because of this, an initial diagnosis of malignant lymphoma by effusion cytology is uncommon, with the literature containing only a few reported cases.3 Although malignant melanoma and lymphoma are differential considerations, in our case, the results of the immunostains argue against these diagnoses.

Compared with other invasive breast carcinomas, lobular carcinomas have a different metastatic pattern, with a high tendency to involve serosal, meningeal, skeletal, and visceral areas.4,5 Metastatic lobular carcinoma has been associated with diffuse infiltration of the uterus, Knitis plastica-like involvement of the stomach wall,5 duodenal obstruction,6 and findings suggestive of ovarian cancer.7 Because of their diffuse growth pattern, infiltrative lobular carcinomas characteristically fail to produce a well-defined mass and therefore are difficult to detect clinically. Involvement of the gastrointestinal tract can present only with a bowel wall thickening on computed tomography.8 The distinction between breast carcinoma and mesothelial cells may be extremely difficult, especially when the malignant cells occur singly and constitute the predominant population of cells in the effusion. The individual cancer cells are relatively small and fairly uniform in size and shape. Spaces resembling windows are present, and intracytoplasmic lumina are not always visible. Infiltrating lobular carcinomas are often hormone-receptor positive, and various sensitivities have been reported for gross cystic disease fluid protein that range from 55% to 90%,9 depending on the histologie subtype.

Categorizing the malignant cells in an effusion can be easy when an obvious population of abnormal cells, discrete from mesothelial cells, is observed or when the cells are present in large tridimensional aggregates. The challenge arises when a single monotonous population of cells with a bland cytology is present. The distinction between neoplasia and reactive mesothelial cells on purely morphologic grounds may be difficult, if not impossible, and ancillary techniques such as immunohistochemistry are valuable tools to the cytopathologist. This is usually not a problem for patients with a history of well-documented neoplasms in which the effusion heralds the progression of disease. However, the cytologie characterization of an effusion can be of paramount importance for the patient in whom the effusion is the presenting symptom of an unknown underlying malignancy.

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