Abstract
Introduction:
Metastatic cancer presents a treatment challenge to clinicians, particularly for patients with bone marrow infiltration. For tumor staging, therapy selection, and prognosis risk stratification, the status of the bone marrow should be known for the presence or absence of metastasis. The study aimed to evaluate the hematological findings and comprehensive analysis of bone marrow in cases of nonhematological malignancies with bone marrow metastasis.
Materials and Methods:
This retrospective study comprised a record retrieval of the departmental archives for the past 6 years. A total of 331 patients with nonhematological malignancies were found, of whom 31.42% (104/331) showed bone marrow metastasis. An integrated clinical approach with bone marrow examination findings and immunohistochemistry whenever necessary was used to achieve a definitive diagnosis of bone marrow metastasis.
Results:
Among the study population, 31.42% (104/331) of patients had nonhematological malignancies that metastasized to the bone marrow. Most of the patients with bone marrow metastasis had anemia, which was found in 77.88% (81/104) of the cases. Leukoerythroblastic reaction was noted in 31.73% (33/104) of the cases, and thrombocytopenia was found in 25% (26/104) of the cases. The most common malignancy with bone marrow metastasis in adults was prostatic adenocarcinoma (28.1%) (9/32) and in pediatric cases, neuroblastoma (53.9%) (52/98).
Conclusions:
It is essential to diagnose nonhematological malignancies that have metastasized to the bone marrow since this necessitates tumor staging, therapy selection, and prognosis risk stratification. To conclude, not a single hematological parameter is predictive of bone marrow metastasis; however, unexplained anemia, a leukoerythroblastic blood picture, and thrombocytopenia in peripheral blood should raise suspicion for bone marrow metastasis in cases of nonhematological malignancies.
Keywords: Bone marrow aspirate, bone marrow biopsy, bone marrow metastasis, hematological findings, immunohistochemistry, nonhematological malignancies, peripheral blood smear
Résumé
Introduction:
Le cancer métastatique présente un défi de traitement pour les cliniciens, en particulier pour les patients présentant une infiltration de moelle osseuse. Pour la stadification tumorale, la sélection du traitement et la stratification du risque de pronostic, l’état de la moelle osseuse doit être connu pour la présence ou l’absence de métastases. L’étude visait à évaluer les résultats hématologiques et l’analyse complète de la moelle osseuse dans les cas de tumeurs malignes non hématologiques avec métastases de la moelle osseuse.
Matériel et méthodes:
Cette étude rétrospective comprenait une récupération des archives ministérielles des 6 dernières années. Un total de patients atteints de tumeurs malignes non hématologiques ont été trouvés, dont 31,42% (104/331) présentaient des osmétastases médullaires. Une approche clinique intégrée avec les résultats de l’examen de la moelle osseuse et l’immunohistochimie chaque fois que nécessairea été utilisé pour établir un diagnostic définitif de métastases médullaires.
Résultats:
Dans la population étudiée, 31,42 % (104/331) des patients présentaient des tumeurs malignes non hématologiques qui se métastasaient à la moelle osseuse. La plupart des patients atteints de métastases de la moelle osseuse présentaient une anémie, qui a été trouvée dans 77,88% (81/104) des cas. Une réaction leucoérythroblastique a été observée dans 31,73 % (33/104) des cas, et une thrombocytopénie a été observée dans 25 % (26/104) des cas. La tumeur maligne la plus fréquente associée aux métastases de la moelle osseuse chez l’adulte était l’adénocarcinome de la prostate (28,1 %) (9/32) et, chez les enfants, le neuroblastome (53,9 %) (52/98).
Conclusions:
Il est essentiel de diagnostiquer les tumeurs malignes non hématologiques qui ontmétastasé à la moelle osseuse car cela nécessite une stadification tumorale, une sélection thérapeutique et une stratification du risque de pronostic. Pour conclure, pas un seul paramètre hématologique n’est prédictif des métastases de la moelle osseuse; Cependant, une anémie inexpliquée, une image sanguine leucoérythroblastique et une thrombocytopénie dans le sang périphérique devraient faire suspecter des métastases de la moelle osseuse en cas de tumeurs malignes non hématologiques.
Mots-clés: Aspiration de moelle osseuse, biopsie de la moelle osseuse, métastases de la moelle osseuse, résultats hématologiques, immunohistochimie, tumeurs malignes non hématologiques, frottis sanguin périphérique
INTRODUCTION
Metastatic cancer presents a treatment challenge to clinicians, particularly for patients with bone marrow infiltration. In cancer patients, the breast, prostate, stomach, and lungs are the principal sites of bone marrow metastasis among adults, and neuroblastoma, followed by Ewing’s sarcoma, are the most common malignancies among the pediatric age group.[1,2] Any tumor that has the potential to spread through the hematogenous route might affect the bone marrow. Hematological cancers frequently involve the bone marrow; nevertheless, diagnosing nonhematological cancer specifically from the marrow is uncommon. Anemia and cytopenias are common first symptoms in patients with bone marrow metastasis.[2] To ascertain the stage of cancer, prognosis, course of therapy, and chemotherapeutic response, it is crucial to find the status of the bone marrow for metastatic deposits.[3] The incidental identification of metastatic disease in bone marrow aids physicians in their search for the primary tumor and indicates a dismal prognosis.[3,4] A bone marrow examination is an inexpensive and accurate test to find metastasis in patients with underlying cancer. The likelihood of the identification of bone marrow metastasis has significantly risen as a result of the recent development of innovative diagnostic and sensitive techniques for the identification of disseminated tumor cells, including reverse transcriptase polymerase chain reaction, and flow cytometry.[5,6] When a metastatic deposit has been inadvertently identified during a bone marrow examination in an unknown case of cancer, the pathologist is faced with a challenging situation.[7] This study aimed to access the hematological findings and comprehensive analysis of bone marrow in cases of nonhematological malignancies with bone marrow metastasis.
MATERIALS AND METHODS
This was a 6-year retrospective cross-sectional study of bone marrow aspiration smears and biopsies performed at the Department of Pathology, King George Medical College, Lucknow. Records were retrieved from the Leukemia-Lymphoma Lab archives to find out hematological parameters such as hemoglobin, total leukocyte count, platelet count, nucleated red blood cells, and immature myeloid cells in the peripheral blood of the patients, along with marrow examination and immunohistochemistry findings. The study included cases of nonhematological malignancies from August 2016 to July 2022 in whom a bone marrow examination was performed at initial presentation. Bone marrow analysis was performed in 311 cases of nonhematological malignancies and was divided into three groups.
Group I: Biopsy-proven cases of nonhematological malignancy for staging, and/or presented with cytopenias/bony lesions (n = 249)
Group II: Symptomatic cytopenias or bony lesions associated with clinically suspected bone marrow metastases of unknown underlying cancer (n = 45)
Group III: Incidentally detected bone marrow metastases in clinically unsuspected cancer (n = 17).
The study excluded patients who had hemolymphoid malignancies or were on chemotherapy, and a bone marrow examination was conducted to look for residual disease. The cases with incomplete records were also excluded from the final study.
As per standard protocols, two bone marrow aspirates and two biopsy impression smears were prepared and stained with Leishman’s stain in each case. A 1.5-cm core was taken, preserved in 10% formalin, decalcified in 13% formic acid, and subjected to standard processing. Hematoxylin and eosin (H and E) stains were applied to the bone marrow biopsy. The presence of atypical cells was specifically checked in detail on bone marrow smears and biopsy sections. The following parameters were examined in bone marrow biopsy sections: Cellularity, normal hematopoietic components, the presence or absence of metastatic nonhematological atypical cells, and assessment of tumor burden according to the criteria of Frisch et al.[8] A suitable immunohistochemical panel was employed on a bone marrow biopsy to make a definitive diagnosis of primary malignancy whenever necessary according to the morphology and pattern of metastatic tumor cells in light of the clinical history and radiological findings, as outlined below:
Pan CK, CK5/7, CK-7, Epithelial membrane antigen (EMA), Prostate specific antigen (PSA), CDX-2, CK-20, Napsin, TTF1, GATA-3, ER/PR, WT-1, Calretinin, CD56, Synaptophysin, Chromogranin, LCA, and S100 in Undifferentiated Carcinoma; Vimentin, Desmin, SMA, myogenin, S100, and CD99 in Sarcoma; and Pan CK, Vimentin, Desmin, SMA, myogenin, CD99, NSE, LCA, CD99, and CK in round cell tumor morphology In the present study, conventional descriptive statistics were used.
RESULTS
Nonhematological malignancies affected the bone marrow in 31.42% (104/331) of the cases, with group I accounting for 62.50% (65/104) of these cases, followed by group II for 21.15% (22/104), and group III for 16.35% (17/104) [Table 1]. These 104 cases with bone marrow involvement were analyzed in detail, including the peripheral blood, marrow aspiration smears, the slides from the bone marrow biopsies, immunohistochemistry, and the bone marrow case records.
Table 1.
Frequency of distribution of cases among different groups
| Groups | Total number of cases | Number of cases positive for bone marrow metastasis |
|---|---|---|
| Group I | 249 | 65 |
| Group II | 45 | 22 |
| Group III | 17 | 17 |
Bone marrow indication for different groups
Group I: Consisted of 249 cases of known biopsy-proven primary malignancy; out of these patients, the staging was the primary grounds for examining the bone marrow in 199 of the cases. In the remaining 50 patients, an examination of the bone marrow was performed because of unexplained hematological abnormalities such as anemia, cytopenias, leukoerythroblastic blood picture, and bony lesions identified during the radiographic evaluation
Group II: These 45 individuals had a clinical suspicion of bone marrow metastasis because of skeletal lytic lesions and were evaluated for anemia, cytopenias, and leukoerythroblastic anemia
Group III: Consisted of 17 cases in whom there was no clinical suspicion of malignancy, but bone marrow metastasis was found incidentally. The primary reason for examining the bone marrow was to look for cytopenias and/or bony abnormalities that could not be explained. Morphologic characteristics, in conjunction with immunohistochemistry, and in-depth clinical and radiographic evaluation, all contributed to the determination of the primary tumor in each of these cases.
There were 163 adult cases and 168 pediatric cases out of a total of 331 patients. The involvement of the bone marrow was seen in 23.31% (38/163) of adult cases and 39.29% (66/168) of pediatric cases [Table 2]. In the present study, 72.12% (75/104) of the individuals with bone marrow metastasis were male, and 27.88% (29/104) were female. The male-female ratio was 2.6:1. In the study population, a 6-month-old child and an 85-year-old patient were the youngest and oldest patients, respectively.
Table 2.
Frequency of bone marrow metastasis among the study population
| Groups | Total number of cases | Number of cases positive for bone marrow metastasis |
|---|---|---|
| Adult patients | 163 | 38 |
| Pediatric patients | 168 | 66 |
| Total patients | 331 | 104 |
Hematomorphological findings of peripheral blood smears
Anaemia was the most common hematological finding as a result of bone marrow metastasis in 77.88% (81/104) patients, followed by thrombocytopenia and leukopenia in 25% (26/104) and 8.65% (9/104) patients, respectively. Twenty-one patients (20.19%) had bi-cytopenia and seven patients (6.73%) presented with pancytopenia. The presence of nucleated red blood cells and immature granulocytes in peripheral blood was another important hematological finding noted in 31.73% (33/104) cases with bone marrow metastasis [Table 3].
Table 3.
Hematomorphological findings in nonhematological malignancy with the bone marrow metastasis
| Peripheral blood findings | Number of cases (%) |
|---|---|
| Anemia | 81 (77.88) |
| Thrombocytopenia | 26 (25.0) |
| Leukopenia | 9 (8.65) |
| Bicytopenia | 21 (20.19) |
| Pancytopenia | 7 (6.73) |
| Nucleated red blood cells with immature myeloid cells (leukoerythroblastic blood picture) | 33 (31.73) |
The most frequent nonhematological malignancy with bone marrow metastasis in pediatric cases was neuroblastoma 53.06% (52/98) followed by Ewing’s sarcoma/primitive neuroectodermal tumor (PNET) 25% (6/24), rhabdomyosarcoma 20% (1/5), retinoblastoma 17.14% (6/35), and Wilms tumor 16.66% (1/6) [Table 4].
Table 4.
Frequency of bone marrow metastasis in the pediatric cases
| Primary tumor | Number of cases positive for bone marrow metastasis/total number of cases (%) |
|---|---|
| Neuroblastoma | 52/98 (53.06) |
| Ewing’s sarcoma/PNET | 6/24 (25) |
| Rhabdomyosarcoma | 1/5 (20) |
| Retinoblastoma | 6/35 (17.14) |
| Wilms tumor | 1/6 (16.66) |
PNET=Primitive neuroectodermal tumor
The most common malignancy with bone marrow metastasis in adults was prostatic adenocarcinomas 28.12% (9/32), followed by adenocarcinoma lung 25% (5/20), infiltrating ductal carcinoma-breast 25% (3/12), Ovarian serous cystadenocarcinoma 25% (1/4), and Ewing’s sarcoma/PNET 25% (4/16). Gastrointestinal adenocarcinoma 20.29% (14/69), endometroid endometrial adenocarcinoma 20% (1/5), and Transitional cell carcinoma of the urinary bladder 20% (1/5) were the next frequent malignancies with bone marrow metastasis [Table 5].
Table 5.
Frequency of bone marrow metastasis in the adult cases
| Primary tumor | Number of cases positive for bone marrow metastasis/total number of cases (%) |
|---|---|
| Prostatic adenocarcinoma | 9/32 (28.12) |
| Lung adenocarcinoma | 5/20 (25) |
| Infiltrating ductal carcinoma-breast | 3/12 (25) |
| Ovarian serous cystadenocarcinoma | 1/4 (25) |
| Ewing’s sarcoma/PNET | 4/16 (25) |
| Gastrointestinal adenocarcinoma | 14/69 (20.29) |
| Endometroid endometrial adenocarcinoma | 1/5 (20) |
| Transitional cell carcinoma of urinary bladder | 1/5 (20) |
PNET=Primitive neuroectodermal tumor
Bone marrow examination findings in nonhematological malignancies with bone marrow metastasis
Bone marrow aspiration was done in all 331 cases and biopsies were performed in 80.97% (268/331) cases. The 19.03% (63/331) cases where biopsies were not done chiefly belonged to the pediatric age group. Bone marrow metastasis was found in 104 out of 331 (31.42%) cases. In 88.46% (92/104) cases, bone marrow aspiration smears showed metastatic deposits, additionally in four cases metastatic deposits were identified in the bone marrow imprint smears, and in eight cases both aspirate and imprint smears were negative; however, bone marrow biopsy was positive. Of the 104 positive cases, in 75% (78/104) cases, bone marrow biopsies were performed and displayed involvement by malignant cells in all the cases.
In 96 positive cases of bone marrow aspirates including imprint smears, 61 cases showed the morphology of small round cells and 38 of them also displayed rosettes-like structures in cases of neuroblastoma and retinoblastoma [Figures 1 and 2]. Fifteen cases displayed acini-like structures in cases of adenocarcinoma with metastatic clusters and two of which showed the morphology of signet ring cells on a mucinous background in cases of gastric carcinoma [Figures 3 and 4]. In the rest of the 20 cases, bone marrow aspirate smears displayed a moderate to marked degree of pleomorphism with deposition of nests and clusters of tumor cells [Figures 5 and 6].
Figure 1.
Photomicrographs were from a 6-year-old boy who was diagnosed with neuroblastoma after a bone marrow examination through computerized tomography of the whole abdomen and retroperitoneal mass biopsy. (a) Peripheral blood smear showing anemia, immature myeloid cells, and nucleated red blood cells (Leishman, ×400). (b) Bone marrow aspirate smear showing clusters and singly scattered tumor cells (Leishman, ×100). (c) High-power view of bone marrow aspirate smear showing small round cells disposed of in ill-formed rosettes and small clusters (Leishman, ×400). (d) Section of bone marrow biopsy displaying intertrabecular space showing big masses of tumor cells with focally retained hematopoietic cells (H and E, ×100). (e) High power view of bone marrow biopsy showing tumor cells disposed of in nests separated by thin fibrous septae having round nuclei, stippled chromatin, and a moderate amount of cytoplasm (H and E, ×400). (f) Tumor cells are displaying a positive cytoplasmic expression of synaptophysin on immunohistochemistry (×400)
Figure 2.
Photomicrographs from a 4-year-old male patient diagnosed with retinoblastoma with bone marrow metastasis and presented bi-cytopenia at initial presentation. (a) Peripheral blood smear showing bi-cytopenia in the form of normocytic normochromic anemia and leukocytopenia (Leishman, ×400). (b) Bone marrow aspirate smear showing hypercellular smears displaying clusters, rosettes, and singly scattered tumor cells (Leishman, ×100). (c) High-power view of a bone marrow aspirate smear showing tumor cells disposed of in clusters and rosettes (Leishman, ×400). (d) Bone marrow biopsy displaying hypercellular marrow spaces showing diffuse infiltration by tumor cells and disposed of in sheets and ill-formed rosettes (H and E, ×100). (e) High power view of bone marrow biopsy showing tumor cells having central round nuclei, coarse chromatin, and a scant amount of cytoplasm (H and E, ×400). (f) Tumor cells are displaying a positive cytoplasmic expression of synaptophysin on immunohistochemistry (×400)
Figure 3.
Photomicrographs from a 66-year-old male patient who had been diagnosed with prostatic adenocarcinoma after bone marrow examination presented with an osteosclerotic nonspecific spinal lesion and pancytopenia. (a) Peripheral blood smear showing pancytopenia in form of normocytic normochromic anemia, leukocytopenia, and thrombocytopenia (Leishman, ×400). (b) Bone marrow aspirate smear showing hypercellular smears displaying clusters, ill-formed acini, and singly scattered tumor cells (Leishman, ×100). (c) High power view of bone marrow aspirate smear showing tumor cells disposed of in clusters and ill-formed acini with markedly reduced normal hematopoietic precursors (Leishman, ×400). (d) Bone marrow biopsy displaying hypercellular marrow spaces showing diffuse infiltration by tumor cells and disposed of in sheets and glandular spaces (H and E, ×100). (e) High-power view of bone marrow biopsy showing tumor cells having central round nuclei, conspicuous nucleoli, and a scant amount of cytoplasm (H and E, ×400). (f) Tumor cells are displaying a positive cytoplasmic expression of PSA on immunohistochemistry (×400). PSA: Postate specific antigen
Figure 4.
Photomicrographs were taken from a 57-year-old female patient who had been identified as having stomach carcinoma on computerized tomography and presented with leukoerythroblastic blood on a peripheral blood examination. (a) A peripheral blood smear reveals anemia, immature myeloid cells, and nucleated red blood cells (Leishman, ×400). (b) Bone marrow aspirates smear displaying sheets and clusters of tumor cells (Leishman, ×100). (c) A high-powered picture of a bone marrow aspirate smear shows large atypical cells with elongated nuclei and an abundant vacuolated cytoplasm that is hard to see (Leishman, ×400). (d) A section of a bone marrow biopsy with intertrabecular spaces demonstrating total marrow takeover by cancer cells (H and E, ×100). (e) A high-power picture of a bone marrow biopsy shows cancer cells disposed of in glandular spaces lined with atypical cells having eccentric, elongated, hyperchromatic nuclei and a lot of pale vacuolated cytoplasm (H and E, ×400). (f) On immunohistochemistry, tumor cells show positive nuclear expression of CDX2 (×400)
Figure 5.
Photomicrographs from a 64-year-old female patient diagnosed with infiltrating ductal carcinoma-breast having bone marrow metastasis and presented with bi-cytopenia at initial presentation. (a) Peripheral blood smear showing bi-cytopenia in the form of anemia and thrombocytopenia (Leishman, ×400). (b) Bone marrow aspirate smear showing cellular smears displaying clusters and singly scattered tumor cells (Leishman, ×100). (c) High-power view of a bone marrow aspirate smear showing pleomorphic tumor cells disposed of in loose clusters and having high nucleo-cytoplasmic ratio, aniso-karyotic nuclei and scant amount of cytoplasm (Leishman, ×400). (d) Bone marrow biopsy displaying hypercellular marrow spaces showing diffuse infiltration by tumor cells and disposed of in nests, clusters and ill-formed tubules (H and E, ×100). (e) High power view of bone marrow biopsy showing moderately pleomorphic tumor cells having central enlarged round to oval nuclei, coarse chromatin, prominent nucleoli and a scant amount of cytoplasm (H and E, ×400). (f) Tumor cells are displaying a positive nuclear expression of estrogenic receptor on immunohistochemistry (×400)
Figure 6.
Photomicrographs were from a 60-year-old male who was diagnosed with colon carcinoma after a bone marrow examination through computerized tomography of the whole abdomen and endoscopic guided biopsy. (a) Peripheral blood smear showing reduced red blood cell density and normocytic normochromic population (Leishman, ×400). (b) Bone marrow aspirate smear showing clusters and singly scattered tumor cells (Leishman, ×100), (c) High-power view of bone marrow aspirate smear showing cluster of moderately pleomorphic round to oval atypical cells (Leishman, ×400). (d) Section of bone marrow biopsy displaying intertrabecular spaces showing nests and clusters of tumor cells (H and E, ×100). (e) High power view of bone marrow biopsy showing moderately pleomorphic tumor cells displaying enlarged nuclei, fine to coarse chromatin, conspicuous nucleoli and moderate amount of cytoplasm (H and E, ×100). (f) Tumor cells are displaying positive expression of CK20 on immunohistochemistry (×400)
The tumor burden in bone marrow biopsy was assessed and classified using the four-tier system of Frisch et al.[8] classification. The severity of the tumor load was determined using the biopsy of the bone marrow, and it was categorized as follows: (a) microcolonies of single cells or clusters, (b) several tiny tumor foci, (c) one or more big masses with retained hematopoietic marrow, and (d) complete marrow takeover by tumor.[9] Eight cases fell into Category A, six into Category B, 35 into Category C, and 29 cases fell into Category D. Eosinophilia was detected in nine cases of bone marrow biopsies, and reactive plasmacytosis was found in three cases as a result of tumor myelopathy. Bone marrow desmoplasia and necrosis were noted in 32 cases.
DISCUSSION
Involvement of bone marrow by metastasis of nonhematological malignancies is an uncommon finding. The most useful and economical method for identifying bone marrow metastasis in nonhematological cancers is bone marrow examination. Although it is not difficult to identify metastatic cells in bone marrow smears since they seem different from normal hemopoietic cells, occasionally morphology cannot pinpoint the precise location of origin of the primary tumor, especially in cases of unsuspected malignancy. In such cases to narrow down the diagnosis, the morphology and pattern of metastatic tumor cells should be compared to the clinical manifestation along with the meticulous selection of an appropriate panel of immunohistochemical markers. High-grade hematological malignancy may morphologically resemble metastatic nonhematological malignant cells to the bone marrow many times, in these cases, cytochemical stain and flowcytometry help in the differentiation. The bone marrow morphological findings, immunohistochemical profile, and most significantly, clinical history and radiological examination play a vital role in determining the histological type of primary malignancy.[10,11,12,13]
In our study, nonhematological tumor metastasis was found in 31.42% (104/331) of cases which is in concordance with previous Indian studies.[2,10] The stage of the illness, the responsiveness to the chemotherapeutic treatment, and the prognosis, all depend on the status of bone marrow for metastatic tumor deposits.[2]
The most frequent primary nonhematological malignancies with bone marrow metastasis in adults are the lung, breast, stomach, and prostate, and neuroblastoma, retinoblastoma, and rhabdomyosarcoma in children.[3,11] In the present study, prostatic adenocarcinoma was the most frequent primary malignancy of adults that resulted in bone marrow metastasis, accounting for 28.12% (9/32) of cases, followed by lung adenocarcinoma, which accounted for 25% (5/20), infiltrating ductal carcinoma of the breast, which accounted for 25% (3/12), ovarian serous cystadenocarcinoma, accounted for 25% (1/4) and gastrointestinal adenocarcinoma which accounted for 20.29% (14/69) of cases. According to Gupta et al. study, gastric adenocarcinoma (37.5%) was the most common primary tumor with bone marrow metastasis followed by adenocarcinoma of the prostate (25%) and lung adenocarcinoma (25%).[11] A study done by Mehdi and Bhatt et al. showed bone marrow metastasis most commonly in cases of prostatic adenocarcinoma (36%) followed by gastric adenocarcinoma (25%), and carcinoma breast (22.2%).[10] The findings of our study are in agreement with those of earlier research from India and other countries,[13,14,15,16] which showed that prostate and gastrointestinal adenocarcinomas were the two most prevalent malignancies in adults with bone marrow metastasis.
In our study, bone marrow metastasis was found in 53.06% (52/98) neuroblastoma cases, 17.14% (6/35) retinoblastoma cases, 25% (6/24) Ewing’s sarcoma/PNET cases, 20% (1/5) rhabdomyosarcoma and 16.66% (1/6) of Wilms tumor in pediatric patients. Indian studies done earlier on nonhematological small round cell tumors in children also showed similar results.[17,18]
Anaemia is the most significant manifestation of solid tumors with bone marrow metastasis. In our study, 77.88% (81/104) of cases with bone marrow metastasis showed anemia followed by thrombocytopenia in 25% (26/104) and leukopenia in 8.65% (9/104) of cases. Similar results were noted for anemia (66.6%) in a previous study done by Sar et al. They also identified leukopenia in 50% of cases and thrombocytopenia in 83.3% of cases with metastatic bone marrow involvement.[18] The findings of the Ozkalemkas et al. study showed anemia and thrombocytopenia in all of their cases with bone marrow metastasis. Unexplained cytopenia in cases with unanticipated nonhematological malignancies was one of the primary causes for bone marrow assessment in their investigation. They said that the existence of microangiopathic hemolytic anemia and a leukoerythroblastic blood profile should necessitate a bone marrow assessment.[19] Mehdi and Bhatt also noted anemia and thrombocytopenia in 71.4% and 45.1% of their patients with bone marrow metastasis, respectively.[10]
In the present study, 31.73% (33/104) of the patients displayed nucleated red blood cells and immature myeloid cells and 20.19% (21/104) of the patients had bi-cytopenia followed by 6.73% (7/104) patients had pancytopenia in their peripheral blood examination. In cases of nonhematological cancer with bone marrow metastasis, leukoerythroblastic blood picture, and cytopenias are frequently seen.[20] Mehdi and Bhatt noted pancytopenia in 19.3% of their patients with bone marrow metastasis.[10] A study done earlier also noted leukoerthroblastic reaction in 26% of cases that had marrow infiltration by nonhematological malignancies.[2]
In the bone marrow, nonhematological malignant cells often form cohesive cell clusters with a desmoplastic stromal response, which makes them simple to identify from hematological malignancy. Rarely, myeloid neoplasms may display uncommon histologic patterns with cellular characteristics that resemble metastatic carcinoma. These abnormal patterns may include clusters of infiltration of large and atypical immature cells with basophilic cytoplasm and cytoplasmic vacuoles.[21]
There have been a few studies in the past that suggest the superiority of bone marrow biopsy over aspirate smears in the detection of metastatic tumor.[22,23] This is due to the fact that deposits in the marrow may frequently evoke a desmoplastic response and focal, which may cause aspirates to be negative. The biopsy should be performed in multiple sections so that a significantly larger amount of the bone marrow can be examined and so that infiltration may be identified in more cases.[9] According to the findings of Singh et al., a bone marrow biopsy was more effective than aspiration in the detection of cancer (97% vs. 72%).[22] The findings of our study, which compared the sensitivity of a biopsy to that of an aspiration (92.30% vs. 100%), were very similar.
In 32 of the patients with nonhematological malignancies with bone marrow involvement, stromal alterations such as necrosis and sclerosis were reported in bone marrow biopsy. Tumour myelopathy, including eosinophilia and plasmacytosis, was observed in 12 of the cases. A variety of related signs were detected, such as osseous metaplasia, desmoplastic alterations, granulomas, and necroinflammatory reactions in bone marrow biopsies of metastatic nonhematological malignancies infiltrating marrow in a few previous studies. These morphological findings may contribute to suggesting bone marrow metastasis.[13] The present study was retrospective and only carried out at one center, which was two of its noted limitations.
CONCLUSIONS
It is essential to diagnose nonhematological malignancies that have metastasis to the bone marrow since this necessitates tumor staging, therapy selection, and prognosis risk stratification. Comprehensive bone marrow morphological evaluation, the pattern of distribution of tumor cells, and the intelligent application of an appropriate immunohistochemical panel remain the gold standard for definitive diagnosis of bone marrow metastasis especially in cases without clinical suspicion. To conclude, not a single hematological parameter is predictive of bone marrow metastasis in nonhematological malignancies, however unexplained anemia, leukoerythroblastic blood picture, and thrombocytopenia should raise suspicion for bone marrow metastasis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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