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Abstract
Phyllodes tumors (PTs) are uncommon biphasic breast neoplasms constituting 0.5 to 1.0% of all breast tumors. Malignant PTs form a very small proportion of these and may metastasize, especially to the lungs and bones. Aggression and metastatic potential are accentuated in tumors exhibiting heterologous differentiation. Metastases to the gastrointestinal tract (GIT) have seldom been reported and are often confined to a segment of the digestive tract. In the absence of relevant clinical history, such patients presenting with gastrointestinal symptoms can lead to diagnostic perplexities. We report a unique case of a malignant PT with extensive osteosarcomatous differentiation and widespread metastases to the GIT.
Keywords: Breast, malignant phyllodes tumor, phyllodes tumor, gastrointestinal metastases, heterologous differentiation
How to cite this article: Introduction 
Phyllodes tumor (PT) is an example of a biphasic breast neoplasm, constituting 0.5 to 1.0% of all breast tumors.[1] On the basis of gross (expansile or permeative borders) and histological characteristics (stromal hypercellularity, overgrowth, atypia, and mitosis), PTs are classified into benign, borderline, and malignant sub-types; around 75% of these are benign.[2] Although all types of PTs have a propensity to recur locally, only the malignant sub-type has a metastatic potential, targeting the lungs and bones.[2] Additionally, malignant PTs with heterologous differentiation are also known to be associated with an aggressive behavior and a greater metastatic potential. Metastasis to the gastrointestinal tract (GIT) is very unusual with only sporadic reports. We report a case of malignant PT with osteosarcomatous differentiation that had widespread metastases to the different parts of the GIT. To the best of our knowledge, a similar case has never been reported in the literature.
Case Report A 55-year-old woman, with a past history of right mastectomy, was brought to the emergency department with 2-day complaints of severe abdominal pain, distension, and constipation. On clinical examination, the patient was in poor general condition and unconscious. There was moderate abdominal distension. Hematological investigations revealed anemia (Hb: 9.0 g/dL), leukopenia (total leukocyte count: 2,200/cmm), and prolonged prothrombin time of 21.3 seconds (control of 13.0 seconds). Routine biochemical investigations were normal. Based on the above findings, a clinical impression of perforative peritonitis was made. However, before the patient could be taken for surgical exploration, her condition deteriorated rapidly and she succumbed.
A complete autopsy was performed. External examination revealed a 12-cm long, healed mastectomy scar on the right anterior chest wall, medially extending from the fifth intercostal cartilage and running obliquely toward the axilla [Figure 1]. Nodular, hard swellings were noted on the right arm [6 cm in diameter, [Figure 1]] and forearm (2 cm in diameter). On in situ and systemic examinations, the most remarkable feature was extensive metastases of the GIT. There was a large (12 × 10 × 6 cm), fungating, intraluminal jejunal mass with infiltration of its wall. The mass was firm to feel with a gray-white glistening lobulated cut surface with foci of necroses and hemorrhage [Figure 2]a. The overlying serosa was bosselated, markedly congested, and covered with exudate [Figure 2]b. The stomach and rest of the intestines (including the duodenum) showed multiple mucosal nodules ranging in sizes from 0.8 to 1.8 cm with similar appearances. One such small bowel nodule showed a perforation, covered by greenish exudate, leading to peritonitis [Figure 2]c and [Figure 2]d. The mesentery revealed two large [8 cm and 5 cm in diameter, [Figure 3]a] tumor deposits. Large deposits were also seen in the lingula and left lower lobe [Figure 3]b and [Figure 3]c.
Figure 1: Right-sided mastectomy scar (white arrow) and a nodular, hard swelling on the right upper limb (black arrow) were seen on general examination
Figure 2: (a) Large, fungating jejunal mass with a gray-white, fleshy cut surface showing necrosis and hemorrhage; (b) the overlying serosa is bosselated, markedly congested, and covered with exudates; (c) mucosal and (d) serosal aspects of the jejunal segment showing a perforated tumor nodule
Figure 3: (a) Metastatic tumor nodule in the mesentery; (b) left hilar metastatic mass; (c) lobulated gray-white on cut surface with additional intra-parenchymal deposit in the lower lobeThe histological examination of all the mass lesions revealed similar morphology. The lesions were composed of atypical, mitotically active polygonal to spindle-shaped cells arranged in sheets [Figure 4]a. They had moderate pale eosinophilic cytoplasm and pleomorphic vesicular nuclei with prominent nucleoli. Binucleate and multinucleate giant cells and osteoclast-like giant cells were also seen [Figure 4]b. The striking feature was the presence of abundant thin lacy osteoid rimmed by the tumor cells [Figure 4c]. No epithelial component was identified. This histology was suggestive of metastatic osteosarcoma. The thyroid too showed similar microscopic tumor deposits. All the other organs were unremarkable.
Figure 4: (a) Polygonal to spindle-shaped tumor cells arranged in sheets (H and E ×100); (b) tumor cells with a moderate amount of cytoplasm, pleomorphic vesicular nuclei, prominent nucleoli, and brisk mitotic activity, and binucleate and multinucleate tumor giant cells also seen (H and E ×250); (c) abundant thin lacy osteoid rimmed by the tumor cells (H and E ×400); (d) mastectomy specimen showing a large fungating growth replacing the entire breast; (e) gray-white, fleshy cut surface with areas of hemorrhage and necrosesWe retrieved the gross images of the previous mastectomy specimen [Figure 4]d and [Figure 4]e along with the histopathology report of a malignant PT showing foci of osteosarcomatous differentiation (vimentin positive, pan-cytokeratin negative, and Ki 67 index of 60 to 70%). Based on all the above findings, we gave the final cause of death as malignant PT with heterologous osteosarcomatous differentiation and disseminated metastases with perforative peritonitis.
Discussion Small intestinal obstruction and subsequent perforation were the important autopsy findings in this report of malignant PT with multi-focal gastrointestinal metastases. Metastatic tumors can involve any part of the gut, but the small intestine is the site of predilection (~70%) where metastatic lesions outnumber the primary neoplasms.[3] This is followed by the colorectum (5–10%), esophagus (2.7%), and stomach (2.6%). Apart from direct extension of intra-abdominal malignancies, the most common cancer to metastasize to the small intestine is the cutaneous melanoma, followed by breast, lung, ovarian, and testicular tumors and they occur as single or multi-focal nodules.[3] Metastases from a sarcoma are extremely rare and their incidence is unknown.[4]
Among the breast primaries, lobular carcinoma has the highest incidence for metastasis to the GIT, whereas PT metastasis is extremely rare, occurring as a late event often preceded by local recurrence and/or metastases to other organs. Only 10 cases of GIT metastases of malignant PT have been reported in the last 10 years [Table 1].[1],[5],[6],[7],[8],[9],[10],[11],[12],[13] The clinical presentation depended on the size and location of the tumor. All the cases involved a single segment of the GIT, most commonly the small intestine (seven patients),[1],[5],[6],[7],[9],[10],[11] where a single large mass caused obstruction or intussusception. The gastric metastases seen in three patients[8],[12],[13] occurred as single or multiple nodules, clinically presenting with upper GI bleed and anemia. Only two cases showed malignant heterologous elements (chondrosarcomatous differentiation[11] and mixed chondrosarcomatous and osteosarcomatous differentiation[5]).
In our case, metastases involved multiple parts of the GIT, namely, the stomach, small bowel (jejunal mass, multiple duodenal, and ileal nodules), large bowel, and the mesentery. Such widespread metastasis involving multiple parts of the GIT is unique and, to the best of our knowledge, has never been reported in the literature. The combination of the past history of a breast malignancy and the fact that bone-forming tumors presenting in the bowel are rarely encountered, the possibilities in our case become relatively limited. Had it been a pure malignant mesenchymal tumor of the breast with the absolute absence of epithelial component, a primary sarcoma of the breast (such as an osteosarcoma) and a metaplastic carcinoma with mesenchymal differentiation would have been considered in the differentials. Primary osteosarcomas of the breast are extremely rare with less than 150 cases reported in the literature.[14] Past history of radiation therapy is an important risk factor, which was absent in our patient. Moreover, a pure breast sarcoma ought to be diagnosed only after thorough sampling and immunohistochemistry revealing p63, broad-spectrum keratin, and high-molecular weight keratin negativity. However, the clinical outcomes of primary breast sarcomas and malignant PTs appear to be similar, raising questions on the significance of this pathologic distinction. A metaplastic carcinoma, on the other hand, is a rare malignant tumor of epithelial origin that exhibits non-glandular morphologies such as squamous, spindle cell, chondroid, and osteoid features. In contrast to the PT, its epithelial component is malignant and the spindled component may be positive for high molecular weight keratin or p63. However, this distinction based on immunohistochemistry is also not absolute and exceptions exist.
Thus, we would like to emphasize on the fact that metastases of malignant PTs can sometimes exhibit such extensive heterologous elements, leading to diagnostic confusion, particularly when the patient presentation is atypical or in the absence of relevant details/report of the primary lesion. In conclusion, this is a very rare and unique case of malignant PT with extensive metastases to the GIT (along with other organs) showing osteosarcomatous differentiation and presenting as small bowel obstruction, and therefore, pathologists should be aware of this possibility, especially in the presence of heterologous elements. This case also highlights the grave prognosis of PT with osteosarcomatous differentiation.
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References 
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CheckDOI: 10.4103/ijpm.ijpm_379_21
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