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CASE REPORT Table of Contents  
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Liver metastasis of breast carcinoma: An unusual presentation and growth pattern

1 Department of Pathology, Uludag University Faculty of Medicine, Bursa, Turkey
2 Department of Medical Oncology, Uludag University Faculty of Medicine, Bursa, Turkey

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Date of Submission21-Dec-2021
Date of Acceptance09-Jan-2022
Date of Web Publication13-Jan-2023


Breast carcinoma is one of the tumors that frequently metastasize to the liver. Extramedullary hematopoiesis (EMH) usually occurs due to insufficient medullary hematopoiesis. In this case report, we present a female patient with sinusoidal breast carcinoma metastasis and extramedullary hematopoiesis in liver biopsy. A 63-year-old female patient with history of breast carcinoma was admitted to our center with respiratory distress. Pleural effusion was detected and thoracentesis was planned. Treatment was given after detection of non-mycobacterial tuberculosis bacillus in the thoracentesis fluid. Antibiotherapy was terminated due to elevation of liver enzymes and bilirubin. The patient's clinical status was evaluated and treatment was re-initiated. The patient did not have any mass lesion in the liver. Tru-cut biopsy was performed to evaluate a possible tuberculosis involvement in the liver. The diagnosis of metastatic breast carcinoma located in the sinusoidal area and cholestatic liver with extramedullary hematopoiesis foci was given using the histomorphological, immunohistochemical and histochemical findings. Radiological evaluation has an important role in staging of malignancies. However, it should be kept in mind that hepatic metastases may present without formation of a mass lesion, and unexpected laboratory results of cases without abnormal radiological features should raise the suspicion of a metastasis. Such materials should be evaluated in detail by making multiple serial sections in the pathology laboratory. Rare metastatic tumor growth patterns not causing a mass lesion such as sinusoidal or portal pattern, should also be kept in mind.

Keywords: Cholestasis, extramedullary, hematopoiesis, liver, metastasis

How to cite this URL:
Özşen M, Uğraş N, Yerci &, Deligönül A. Liver metastasis of breast carcinoma: An unusual presentation and growth pattern. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Nov 30]. Available from:

   Introduction Top

Although different prognostic biomarkers for malignancies, both at the histomorphological and molecular level, continue to be investigated, distant organ metastases still is the most important parameter determining prognosis.[1]

Metastases to the liver are frequent due to the organ's dual circulatory system. Among the secondary liver tumors, carcinoma metastases are the most common and breast carcinoma metastasis is one of the leading ones. Distant organ metastasis is detected in approximately 5% of breast carcinomas at the time of diagnosis, and in 10–15% of them within the first 3 years after diagnosis.[2],[3] Clinical and radiological findings are usually sufficient in the diagnosis of secondary tumors that form mass lesions.[4]

Here, we present a female patient who presented with liver test abnormality and was diagnosed with sinusoidal breast carcinoma metastasis and extramedullary hematopoiesis (EMH). We aim to discuss the clinical and histopathological findings of this rare association with the relevant literature.

   Case Report Top

A 63-year-old female patient, who was diagnosed with invasive breast carcinoma, no special type 4 years ago, applied to the emergency department with respiratory distress and was hospitalized for further diagnosis and treatment. Patient's history revealed that she received adjuvant chemoradiotherapy. During routine follow-up, metastases in the cervical, axillary, mediastinal lymph nodes, bone, and recurrence in the right breast were detected.

Physical examination and radiological evaluations in the emergency department revealed pleural effusion and the patient underwent thoracentesis. Treatment with isoniazid and ethambutol was given after detection of non-mycobacterial tuberculosis bacillus in the thoracentesis fluid. Increase in serum AST, ALT, GGT (41, 39 and 321 U/L, respectively; normal value: 11–25, 7–28, and 9–36 U/L), and elevation in serum total and direct bilirubin values (1 73 and 0.95 mg/dL, respectively; normal value: 0.2–1.2 and 0.00–0.50 mg/dL, respectively) were detected during treatment. Liver ultrasonography showed normal-sized liver, regular contours, and homogeneous echogenicity of the parenchyma. No lesion or dilatation in the intrahepatic bile ducts was detected. The antibiotherapy was terminated and the liver enzymes and bilirubin values were followed up. After decrease in liver enzyme and bilirubin values in 2 weeks, treatment was restarted with close liver function follow-up. When the patient had reincreased values, tru-cut biopsy of the liver was performed in order to evaluate hepatic involvement of an infectious agent.

In the microscopic evaluation of the liver biopsy, hepatocanalicular pure cholestasis was present and two different types of cells were observed in the sinusoidal area. The first group of cells was cytologically atypical with normochromatic nuclei, basophilic cytoplasm, and inconspicuous nucleoli. Atypical cells were forming groups in some areas and some of them included intracytoplasmic mucin. The second cell type showed hyperchromatic nucleus, high nuclear/cytoplasmic ratio, and varying cell size [Figure 1].
Figure 1: (a) Two different types of cells were observed in the sinusoidal area. The first group of cells (marked with asterix) was cytologically atypical and the second cell type (marked with arrow) showed hyperchromatic nucleus, high nuclear/cytoplasmic ratio, and varying cell size (H&E ×400). (b) The first atypical cells (marked with asterix) were forming groups in some areas and some of them included intracytoplasmic mucin (H&E ×400)

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Immunohistochemically, the formerly identified atypical cells showed expression of pancytokeratin (CK), cytokeratin 7 (CK 7), GATA3, and mammoglobulin. CK 20, estrogen receptor (ER), progesterone receptor (PR), caudal-related homeobox 2 (CDX2), thyroid transcription factor 1 (TTF-1), and carbohydrate antigen 19-9 (CA19-9) were not expressed in these cells. Intracytoplasmic mucin was shown histochemically. The second cell population with the hyperchromatic nuclei did not express CK, CK 7, GATA3, or mammoglobulin [Figure 2]. With the morphological and immunohistochemical findings at hand, atypical cells were evaluated as metastatic breast carcinoma while the second cell population was considered to be compatible with EMH foci containing precursors of erythroid and myeloid series. The case was diagnosed with sinusoidal metastatic breast carcinoma and cholestatic liver with EMH.
Figure 2: The finding of immunochemistry and histochemistry of the first atypical group (marked with asterix). (a) Cytoplasmic positivity to histochemical staining with musicarmen (×400), (b) strong positivity to immunohistochemical staining with CK 7 (×200), (c) mammoglobulin (×400), and (d) GATA 3 (×400)

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The patient died due to poor general condition and respiratory distress following the liver biopsy procedure.

   Discussion Top

Several different histopathological growth patterns of hepatic metastases have been described in various studies. These are desmoplastic, replacement, pushing, sinusoidal, and portal-type growth patterns. While desmoplastic, replacement, and pushing growth patterns are commonly seen in metastases, sinusoidal and portal patterns are rarely observed.[1]

The determination of histopathological growth patterns and their effects on treatment and survival have been investigated in various researches. In their study, Frentzas et al.[5] observed that tumors with more than 50% replacement growth pattern responded worse to treatment compared to tumors with more than 50% desmoplastic growth pattern. In several studies, it has been shown that histopathological growth pattern of various tumors, such as colorectal cancer, uveal melanoma, malignant melanoma, breast carcinoma, and hepatocellular carcinoma, is effective on patient survival.[6] In Nielsen et al.'s[7] research investigating the effect of growth patterns of colorectal liver metastases on overall survival, the best survival rate, with 61%, was observed in cases with a desmoplastic growth pattern, while the poorer prognosis was seen in cases with the replacement growth pattern.

Breast cancer is one of the most common tumors that metastasize to the liver, and replacement growth pattern is present in the majority.[1] This allows secondary breast tumors to be detected as mass lesions by radiological imaging techniques. However, there are rare reported cases with sinusoidal growth pattern. In this type of growth pattern, in which tumor cells do not make cell-to-cell contact with liver parenchyma and spread without forming a mass lesion, no significant radiological findings are found. Patients with these tumors usually present with signs of hepatitis or liver failure. Some cases may progress to fulminant liver failure before the detection of the metastasis. The degree of elevation of liver enzymes is directly proportional to the degree of sinusoidal involvement.[8]

In tumors with a sinusoidal growth pattern, the liver size may be slightly increased or there might be no pathological features in the macroscopic evaluation. The presence of tumor cells in the sinusoidal area causes certain parts of the liver to remain hypoxic, causing infarcts. Infarct areas are macroscopically pale looking or easily dispersible if necrosis has developed. In rare cases where the tumor causes a desmoplastic reaction, the liver may have a cirrhotic appearance.[9] Microscopic evaluation should include careful evaluation of the parenchyma, sinusoidal and portal areas, keeping the histopathological growth patterns in mind. It should be noted that both primary and secondary tumors can show all types of growth patterns. In addition to immunohistochemical and histochemical studies, the patient's history, physical, and radiological examination findings and laboratory results are very helpful in making the correct diagnosis.

EMH is an entity that should be kept in mind in the histopathological evaluation of biopsies, since it is both a mimic and a companion of liver malignancies. To avoid misdiagnosis, it should be kept in mind that megakaryocytes can mimic atypical cells, especially in imprint materials.[10]

Hepatic metastasis in breast cancer is important in its staging. It should be kept in mind that hepatic metastases may present without forming a mass lesion. Unexpected increase in laboratory values in cases without any abnormal radiological findings should be carefully evaluated. Liver biopsy materials from patients with a former diagnosis of any neoplasia need to be histopathologically examined in detail by serial sections.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

van Dam PJ, van der Stok EP, Teuwen LA, Van den Eynden GG, Illemann M, Frentzas S, et al. International consensus guidelines for scoring the histopathological growth patterns of liver metastasis. Br J Cancer 2017;117:1427-41.  Back to cited text no. 1
Park JH, Kim JH. Pathologic differential diagnosis of metastatic carcinoma in the liver. Clin Mol Hepatol 2019;25:12-20.  Back to cited text no. 2
Ellis OV, Hornock SL, Bohan PMK, Dilday JC, Chang SC, Bader JO, et al. Impact of hepatic metastasectomy in the multimodal treatment of metastatic breast cancer. J Surg Res 2021;268:650-9.  Back to cited text no. 3
Vyas M, Jain D. A practical diagnostic approach to hepatic masses. Indian J Pathol Microbiol 2018;61:2-17.  Back to cited text no. 4
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Frentzas S, Simoneau E, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, et al. Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. Nat Med 2016;22:1294-302.  Back to cited text no. 5
Latacz E, Van Dam P, Vanhove C, Llado L, Descamps B, Ruiz N, et al. Can medical imaging identify the histopathological growth patterns of liver metastases? Semin Cancer Biol 2021;71:33-41.  Back to cited text no. 6
Nielsen K, Rolff HC, Eefsen RL, Vainer B. The morphological growth patterns of colorectal liver metastases are prognostic for overall survival. Mod Pathol 2014;27:1641-8.  Back to cited text no. 7
Simone C, Murphy M, Shifrin R, Toro TZ, Reisman D. Rapid liver enlargement and hepatic failure secondary to radiographic occult tumor invasion: Two case reports and review of the literature. J Med Case Rep 2012;6:402.  Back to cited text no. 8
Allison KH, Fligner CL, Parks WT. Radiographically occult, diffuse intrasinusoidal hepatic metastases from primary breast carcinomas: A clinicopathologic study of 3 autopsy cases. Arch Pathol Lab Med 2004;128:1418-23.  Back to cited text no. 9
Prieto-Granada C, Setia N, Otis CN. Lymph node extramedullary hematopoiesis in breast cancer patients receiving neoadjuvant therapy: A potential diagnostic pitfall. Int J Surg Pathol 2013;21:264-6.  Back to cited text no. 10

Correspondence Address:
Mine Özşen,
Department of Pathology, Uludag University Faculty of Medicine, Bursa
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_1235_21


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