E-ISSN:2456-1487
P-ISSN:2456-9887
RNI:MPENG/2017/70771

Research Article

Bone Marrow

Tropical Journal of Pathology and Microbiology

2015 Volume 1 Number 1 JUL-DEC
Publisherwww.medresearch.in

Bone Marrow Metastasis- Morphology, Molecular features and Diagnosis: A Study from a regional cancer Centre in India

Namrata NR1*
DOI:10.17511/jopm.2015.i1.08

1* Namrata N Rajakumar , Associate Professor, Pathology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India.

Objective: bone marrow biopsies are frequently done for histologically documented malignancies for staging and also in suspected malignancies Bone marrow involvement by solid tumours implicates advanced disease and a bad prognosis..It is important to rule out bone marrow involvement before planning for any definitive, curative treatment hence diligent and exhaustive search for metastatic cells in Bone marrow which aids in accurate staging treatment and prognosis was done.

Materials and Methods: This was a retrospective observational study of bone marrow involvement by solid tumours and their haematological manifestation

Results: Evaluation of Bone marrow evaluation during the past 7 years, in solid malignancies, revealed Out of 772, 342 were pediatric cases and 430 were adult cases. Bone marrow was involved in 82 patients, In adults, bone marrow involvement was diagnosed in 40 cases. Neuroblastoma was the most common malignancy, which involved the bone marrow in pediatric cases. In adults common was neuroendocrine carcinoma metastasis to bone marrow followed by carcinoma breast in women and carcinoma prostate in men.

Conclusion: A diligent and exhaustive search for metastatic cells in Bonemarrow helps in accurate staging treatment and prognosis, morphological examination is still the gold standard for suspected marrow involvement, Use of immunohistochemistry markers on bone marrow biopsies results in a higher detection rate, also aids in picking very few neoplastic cells, thereby helps in detecting early metastasis. Immunohistochemistry may be useful in recognizing some tumors in the marrow and confirming primary tumor origin.

Keywords: Bone Marrow,.Metastasis. IHC, solid malignancies

Corresponding Author How to Cite this Article To Browse
Namrata N Rajakumar , Associate Professor, Pathology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India.
Email:
Namrata NR, Bone Marrow Metastasis- Morphology, Molecular features and Diagnosis: A Study from a regional cancer Centre in India. Trop J Pathol Microbiol. 2015;1(1):36-41.
Available From
https://pathology.medresearch.in/index.php/jopm/article/view/668

Manuscript Received Review Round 1 Review Round 2 Review Round 3 Accepted
2015-09-04 2015-09-11 2015-09-17 2015-09-23 2015-09-30
Conflict of Interest Funding Ethical Approval Plagiarism X-checker Note
None Nil Yes 13.36

© 2015by Namrata NRand Published by Siddharth Health Research and Social Welfare Society. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ unported [CC BY 4.0].

Introduction

Bone marrow biopsies are frequently done for histologically documented malignancies for staging and also in suspected malignancies Bone marrow involvement by solid tumor implicates advanced disease and bad prognosis [1 ]. The tumours most frequently detected in bone marrow biopsies in adults are carcinoma of the breast, lung, prostate stomach colon, kidney and thyroid gland.[2],[3]. Among adult solid tumours, involving bone marrow, breast carcinoma is common in women and prostatic carcinoma in men [3],[4]. The Metastases of solid tumours in the bone marrow are rarely reported, and laboratory findings and clinical presentations are not characteristic [4].

Marrow involvement by Sarcomas is relatively low and tumour cells are invariably seen in groups or clusters. They are generally sharply demarcated, and look alien to the marrow environment [3], [5]. Sometimes marrow involvement is focal and the yield of marrow biopsies is increased by the amount of tissue obtained. [4]

The final step in cancer progression is metastasis and most cancer patients die from metastasis and not from primary disease. [5],[6],[7]. In this study, we attempted to study the haematological picture and clinical picture morphological /IHC in patients with metastasis. This is the study of solid tumors, and metastasis to bone marrow, The period of study was 7 years (2006-2013), from a regional cancer center in India.

Materials and Methods

We at Kidwai Cancer Center retrospectively analysed, medical records of patients with bone marrow metastasis suspected to have non-haematological malignancies and were referred to the Department of Pathology between January 2006 to January 2013, patients records included history, general physical examination, laboratory and radiological data blood and BMA /Biopsy as well as IHC staining. Also, haematological malignancies, lymphoma, and SRCT were excluded in this study. Haemogram details were reviewed. Bone marrow was obtained from the posterior iliac crest by Jamshidi needle. Bone marrow smears and peripheral smears and stained by Romanowsky stains, Bone marrow biopsies were stained with hematoxylin and eosin.

Immunohistochemistry was done to confirm primary tumor site detection in a few cases. The patient’s name, age, gender, diagnosis, and clinical, and radiological findings were noted.

Results

Bone marrow examinations, of solid malignancies patients were evaluated. Out of 772 total cases, 342 were pediatric cases and 430 were adult cases. ( Table 1)

Table 1: Distribution of bone marrow involvement among all patients

number of casesNumber of positive cases
Pediatric cases34242
Adult cases43040
Total77282

Bone marrow was involved in 82 patients.. bone marrow involvement was present in 40 cases, in Adults. The bone marrow was considered to be ‘involved by tumour’ if tumour cells were detected in bone marrow aspirate, biopsy, or both. Female to male ratio was 1;1.5

Table 2: Distribution of bone marrow involvement among Adult patients

Neuroendocrine carcinoma9
Breast cancer8
Prostatic carcinoma7
Colon cancer6
Gastric cancer3
Unknown primary and other7
total40

Anaemia was commonly seen in 28 cases. Leucopenia/neutropenia and thrombocytopenia were seen in 5 cases. Pancytopenia was found in 5 patients 13 patients showed Leuco -erythroblastic anaemia. Bone marrow was normocellular in majority of cases and hypocellular in 2 cases.. in a few cases final diagnosis of solid tumor metastasis was established using IHC markers CK, LCA EMA, PSA, CD99, vimentin, synaptophysin, desmin, etc Among adult solid tumors, involving bone marrow, breast being common in women On H&E 20x Bone marrow Aspiration and Biopsy showed characteristic Metastatic carcinoma breast, atypical cells in clusters with hyperchromatic nucleus and scant cytoplasm. Many cancers especially carcinoma breast and carcinoma prostate are associated with marked desmoplastic reaction, reason for dry tap in a few cases.


patho_668_01.JPG
Figure 1:
On H&E 20x Bone Marrow smears showing Metastatic carcinoma breast

patho_668_02.JPG
Figure 2:
On H&E 20x Bone Marrow smears showing metastatic prostatic carcinoma

We didn’t have any dry tap, carcinoma breast metastatic to marrow had fibrosis. , was a very difficult differential diagnosis of myelofibrosis. There could be difficulty in a few cases which resemble hematopoietic origin because of the giant cells, resembling megakaryocytes.

patho_668_03.JPG
Figure 3:
Metastatic Carcinoma prostate cells in High power

patho_668_04.JPG
Figure 4:
Metastatic Carcinoma prostate cells in low-power, glandular pattern

Discussion

The bone marrow biopsies are frequently done for histologically documented malignancies for staging and also in suspected malignancies Bone marrow involvement by solid tumor implicates advanced disease and bad prognosis [1],[2],[3]. Among adult solid tumors, involving bone marrow, the breast is common in women and prostatic carcinoma in men. Gastric cancer, metastasis was seen in younger patients. Cancer metastasis is the major cause of death in over 90%of patients with solid tumors [3],[4], [5].

Detection increases with bilateral and multiple biopsies [6],[7],[8]. Metastatic marrow morphological diagnosis.IHC is not necessary [8],[9]. The metastatic process is a multi-step cascade including local invasion and migration from the primary tumour, the mechanisms of micrometastasis to the distal tissues are highly regulated and involve numerous intrinsic and extrinsic factors as well as signalling pathways. The factors promoting marrow metastasis are poorly defined. However, this process can be explained by the unique marrow environment that is rich in adhesion molecules, cytokines, chemokines, and growth factors. Cytokines such as IL-6, IL11, and TNF-Seem to contribute to metastasis specifically to the bone and bone marrow [10], [11], [12], [13], [14].

Kopp et al reported that the presence of erythroblasts in the blood smear is highly suggestive of bonemarrow infiltration in breast cancer [ 13 ] Sometimes marrow involvement is focal and the yield of marrow biopsies is increased by the amount of tissue obtained. [8] The tumors most frequently detected in bone marrow biopsies in adults are carcinoma of the breast, lung, prostate stomach colon, kidney and thyroid gland. [2], [3]. Even in the current study commonest was carcinoma breast and carcinoma prostate. Metastatic tumour cells in bone marrow, are invariably seen in groups or clusters. They are generally sharply demarcated, and look alien to the marrow environment [ 2,3,4 ] This is a characteristic feature as hematopoietic origin cancers do not show cohesive clusters., however with extensive involvement individual cells also can be found. Sometimes entire marrow can be replaced. Tumor cells in marrow can be analysed on bone marrow smears, crush particle smears, trephine imprints or bone marrow biopsy. [3],[4].


In the current study, marrow was said to be involved in any one of these had showed metastatic cells. The clinical and prognostic significance of leucoerythroblastic anemia in patients with metastatic prostatic cancer and general patients with disseminated solid tumors is not understood clearly. Leucoerythroblastic anemia has greater transfusion requirements .breast carcinoma involving marrow, the majority were infiltrating duct carcinoma, and bone marrow metastasis in gastric cancers are generally seen in younger patients and poorly differentiated tumours. The prognosis is worsened with poor histology and pancytopenia. Among adult solid tumors, involving bone marrow, the breast is common in women and prostatic carcinoma in men. Many cancers especially carcinoma breast and carcinoma prostate are associated with marked desmoplastic reaction, the reason for dry tap in a few cases. Also is a very difficult differential diagnosis from myelofibrosis. Some cases marked osteosclerosis.[3],[14 ]

Immunohistochemistry may be useful in recognizing some tumors in the marrow .routine IHC is not necessary for detecting marrow involvement. However, IHC may be required when individual tumour cells are scattered in the marrow, especially in invasive lobular carcinoma. [14],[15]. In the current study, all the cases of carcinoma breast were infiltrating duct carcinoma. It's always better to compare the H&E if the foci of metastasis are very small with the IHC reaction.[14] Many studies have confirmed that Molecular markers increase the detection rate of metastasis [16 ] our study lacked the molecular techniques. Immunological quantification of the metastatic cells in bone marrow also is being done. The coexistence of solid tumors and bone marrow metastasis is associated with a deteriorating clinical course and poor prognosis.[3], [4]. The approach to unknown primary lesions should be the same as metastatic lesion analysis in other sites. [8],[14],[15],[16], due to financial constraints our study couldn’t use extensive IHC panels, however, the possibility of neuroendocrine, carcinoma, breast carcinomas, and cancer prostate was suggested in the limited IHC panel.

Immunohistochemistry was done and it showed Synaptophysin and chromogranin expression. In Neuroendocrine carcinomas, breast carcinoma involving marrow showed CK and ER positivity, and prostatic carcinomas showed positivity for CK and positivity for PSA in a case.

A deeper understanding of metastasis is essential for discovery of more effective therapies[ 17]

Conclusion

A diligent and exhaustive search for metastatic cells in Bonemarrow helps in accurate staging treatment and prognosis, morphological examination is still the gold standard for suspected marrow involvement. The tumors most frequently detected in bone marrow biopsies in adults are carcinoma of the breast and, prostate similar to other studies. Immunohistochemistry may be useful in recognizing some tumors in the marrow. IHC is required when individual tumour cells are scattered in the marrow. It's always better to compare the H&E if the foci of metastasis are very small with the IHC reaction. The present study lacked molecular techniques and immunological quantification of metastatic cells in bone marrow which can identify the high-risk disease at diagnosis and during treatment, future studies could concentrate on detecting metastasis early and also on preventing bone marrow metastasis.

Abbreviations: IHC ;Immuno histochemistry, cytokeratin; CK, PSA; prostatic specific antigen

Permission from Institutional Research Board (IRB): Yes

Funding: Nil

Conflicts of interest: none

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